This is the accessible text file for GAO report number GAO-03-182 
entitled 'Bone Marrow Transplants: Despite Recruitment Successes, 
National Program May Be Underutilized' which was released on October 
18, 2002.



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Report to Congressional Committees:



United States General Accounting Office:



GAO:



October 2002:



Bone Marrow Transplants:



Despite Recruitment Successes, National Program May Be Underutilized:



Bone Marrow Transplants:



GAO-03-182:



Contents:



Letter:



Results in Brief:



Background:



NMDP Has Succeeded in Increasing Recruitment of Donors, Including 

Minorities, but May Not Be Able to Equalize Access to Matches:



National Registry May Be Underutilized:



Organizations in the NMDP Network Generally Comply with Its Standards 

and Procedures:



Concluding Observations:



Agency Comments:



Appendix I: Methods of Assessing Registry Utilization:



Method Based on Number of HLA-Identical Sibling Transplants:



Method Based on Number of Preliminary Searches:



Method Based on Incidence of Disease:



Appendix II: How NMDP Achieves Network Compliance 

with Selected Standards and Procedures:



Informed Consent of Donors and Patients:



Criteria for Donor Selection:



Methods to Protect Confidentiality:



Marrow Collection and Transport:



Laboratory Standards:



Donor File Maintenance and Updates:



Appendix III: Comments from the Health Resources and 

Services Administration:



Appendix IV: GAO Contact and Staff Acknowledgments:



Tables:



Table 1: Percentage Increase in Registry Donors, by Racial and Ethnic 

Group, 1998 to 2000, and Current Proportion of Groups on the Registry 

and in the Population:



Table 2: U.S. Patients’ Utilization of the Registry, by Race and 

Ethnicity, 1997 to 2000:



Table 3: Reasons for Preliminary Search Cancellation, January 2000 

through September 2001:



Table 4: Reasons for Formal Search Cancellation, 1997 to 2000:



Table 5: Alternate Approach to the Analysis of U.S. Patients’ 

Utilization of the Registry, by Race and Ethnicity, 1997 to 2000:



Table 6: Average Annual Unrelated Donor NMDP-Facilitated Transplants 

and Estimated Number of Potential Recipients for U.S. Patients with 

Selected Diseases Who Might Benefit from Unrelated Stem Cell 

Transplants, by Race/Ethnicity, 1997 through 2000:



Figure:



Figure 1: Theoretical Probability of Patient’s Finding at Least One 

Matched Donor, by Racial and Ethnic Group, 1988 to 2001:



Abbreviations:



ABMTR: Autologous Blood and Marrow Transplant Registry:



CPI: Continuous Process Improvement:



HHS: Department of Health and Human Services:



HLA: human leukocyte antigens:



HRSA: Health Resources and Services Administration:



IBMTR: International Bone Marrow Transplant Registry:



NMDP: National Marrow Donor Program:



OIG: Office of Inspector General:



OPA: Office of Patient Advocacy:



PBSC: peripheral blood stem cells:



United States General Accounting Office:

Washington, DC 20548:



October 18, 2002:



Congressional Committees:



More than 30,000 people are diagnosed annually with leukemia or other 

blood, metabolic, or immune system disorders, many of whom may die 

without stem cell transplants, using stem cells from bone marrow or 

another source.[Footnote 1] When a patient needs a transplant of 

donated stem cells and no genetically compatible related (family) donor 

is available, the National Bone Marrow Donor Registry (Registry) may 

help the patient search for compatible stem cells from unrelated 

donors. Founded in 1986, the Registry is the largest and most diverse 

list of potential donors in the world. This list currently includes 

more than 4 million donors.[Footnote 2] The Registry is operated by the 

nonprofit National Marrow Donor Program (NMDP) under contract to the 

Department of Health and Human Services’ (HHS) Health Resources and 

Services Administration (HRSA), with additional support from the U.S. 

Navy.[Footnote 3] NMDP coordinates stem cell transplants through its 

network of more than 400 participating organizations, domestic and 

foreign, involved in transplantation, including donor centers, which 

recruit and manage donors; laboratories; blood sample repositories; 

bone marrow collection centers; and transplant centers. NMDP has 

facilitated more than 14,000 transplants since 1987.



Concerns about the Registry have been raised by the HHS Office of the 

Inspector General (OIG) and in our own work. These include the extent 

to which the Registry provides equality of opportunity for patients of 

all racial and ethnic groups to find compatible (matched) unrelated 

donors, the extent to which it is utilized by those in need of stem 

cell transplantation, and the effectiveness of the management of the 

donor centers. We reported in 1992 that the proportions of African 

American and Hispanic donors on the Registry were less than their 

proportions in the U.S. population.[Footnote 4] This imbalance results 

in a decreased likelihood of an individual from a minority group 

finding a match and eventually receiving a transplant because matches 

are more likely to be found from among donors of one’s own group. In an 

effort to address these concerns, a 1996 OIG report recommended that 

HRSA and NMDP reexamine the method used to finance the donor centers 

that recruit volunteers to join the Registry.[Footnote 5] It 

recommended a performance-based method to pay donor centers for 

specific activities including monetary incentives tied to performance 

indicators and emphasizing recruitment and retention of donors, 

especially those from racial and ethnic minority groups.



The National Bone Marrow Registry Reauthorization Act of 1998[Footnote 

6] required, among other things, that the Registry carry out a donor 

recruitment program giving priority to minority and underrepresented 

donor populations, ensure efficiency of operations, and verify 

compliance with standards by organizations that participate in the 

Registry. In addition, the act required that we conduct a study of the 

Registry, including an examination of the extent to which it has 

increased representation of racial and ethnic minority groups so that a 

member of such a group has a probability of finding a match comparable 

to that of a person who is not a member of such a group. In conducting 

this study, we addressed the following questions: (1) To what extent 

have the program’s recruitment efforts increased the enrollment of 

donors, including those from racial and ethnic minority groups, since 

the 1998 act took effect, and has the chance of finding a suitable 

match increased? (2) To what extent is the Registry utilized to search 

for and obtain transplants? (3) Are the donor centers and other 

organizations in the NMDP network complying with its standards and 

procedures?



To answer these questions, we analyzed NMDP data on racial and ethnic 

representation on the Registry from 1998 through 2001 and, to provide a 

broader context for examining these changes, also analyzed data on 

racial and ethnic representation in relation to the patients who 

searched the Registry from 1988 through 2001. In addition, we analyzed 

data provided by the International Bone Marrow Transplant Registry 

(IBMTR)[Footnote 7] on transplants from related donors from 1997 

through 2000, which enabled us to estimate the demand for unrelated 

donor transplants in the United States and relate this estimate to 

Registry utilization by patients searching for donors during this 

period; analyzed NMDP data on matches, canceled searches, and 

transplants obtained for patients needing donors during this period; 

reviewed NMDP’s standards for participating in the Registry; and 

reviewed evidence of compliance with the standards and procedures by 

the organizations that participate. We also interviewed officials of 

NMDP; HRSA; the Department of the Navy; the American Red Cross; and 

selected donor, stem cell collection, and transplant centers. We did 

not independently verify the accuracy of the data provided by NMDP. We 

conducted our work from June 2001 through June 2002 in accordance with 

generally accepted government auditing standards.



Results in Brief:



From 1998, when the National Bone Marrow Registry Reauthorization Act 

was enacted, through 2001, the number of stem cell donors on the 

Registry increased for all racial and ethnic groups. NMDP recruitment 

efforts focused on minority groups appear to have been effective in 

increasing the number of donors from these populations. Since 1998 the 

number of donors on the Registry has increased by 36 percent, and 

increases for minority groups ranged from 30 percent to 53 percent. The 

total of more than 1 million minority donors listed in 2001 contrasts 

with the approximately 80,000 we reported in 1992. The proportional 

distribution of racial and ethnic groups on the Registry was much 

closer to their proportional distribution in the U.S. population at the 

end of 2001 than it was in our 1992 review. However, when viewed as a 

percentage of each group’s proportion of the U.S. population, African 

Americans and Hispanics are underrepresented by 17 and 15 percent, 

respectively. The underrepresentation of minorities is somewhat 

mitigated by the Registry’s efforts to have complete genetic 

information needed for typing on a higher proportion of minority 

donors, which facilitates more rapid matching. For all racial and 

ethnic groups, the theoretical probability of finding a match has grown 

as the Registry size has increased, but equal access to a match may not 

be attainable. Differences among racial and ethnic groups in the rarity 

and variability of the genes responsible for compatibility in 

transplants may mean that the Registry cannot achieve equal probability 

for all groups. Further, devoting many resources in pursuit of a small 

number of rare genetic types may divert resources from other efforts, 

such as recruiting Caucasians and other groups with more common genetic 

types, which might more readily increase the number of matches.



Although the exact number of patients in need of transplants is not 

known, estimates suggest that about one-third of them utilize the 

Registry to search for donors. The number of transplants facilitated by 

NMDP represents about one-tenth of those we estimate to be in need of 

unrelated donor transplants. These figures suggest that the Registry 

may be underutilized for both searching and facilitating transplants. 

From 1997 through 2000, an estimated 44,740 U.S. patients were in need 

of unrelated donor transplants. During this period, physicians for 

approximately 15,000 U.S. patients conducted preliminary searches for 

donors on the Registry, and about 4,000 of these patients obtained 

unrelated donor transplants facilitated by NMDP. About 25 percent of 

formal searches were not completed because stem cells were obtained 

from donors or organizations without the involvement of NMDP.



The organizations that are involved in transplantation and participate 

in the NMDP network generally adhere to NMDP’s standards and 

procedures. NMDP monitors the compliance and performance of these 

organizations with its standards by using several systems of feedback 

and incentives, including site visits. Centers that deviate from NMDP’s 

standards may be placed on probation or suspended or their 

participation in the network may be terminated. In 2001, NMDP required 

24 centers to take corrective actions because they did not meet its 

standards. Further, NMDP reimburses donor centers for services based on 

their performance by offering financial incentives to centers that 

consistently meet donor recruitment goals and financially penalizing 

centers that do not.



In its written comments on a draft of this report, HRSA stated that the 

report provides an accurate and helpful overview of the status of the 

National Bone Marrow Donor Registry. HRSA agreed that other efforts are 

needed in addition to minority recruitment efforts in order to improve 

minority access to unrelated donor transplants, but pointed out that 

the Registry has complete genetic information needed for matching on 

higher proportions of minority donors than it has for Caucasian donors. 

We have clarified this information in the report. HRSA agreed that many 

patients who could benefit from transplants do not utilize the Registry 

but suggested a slightly modified method of determining the number of 

patients in need of transplants. We accepted this suggestion, but note 

that both approaches produce virtually identical estimates of overall 

underutilization. (See app. I.) HRSA also noted that many factors 

affect the time required to complete a search of the Registry and that 

NMDP has completed medically urgent searches in less than a month. We 

have included this clarification in the report. In addition, HRSA 

provided technical comments, which we have incorporated as appropriate.



Background:



Most of the diseases treated by stem cell transplantation involve 

abnormalities of the blood, metabolic, or immune systems. These 

diseases include several forms of cancer as well as certain 

nonmalignant diseases.[Footnote 8] They strike all races, although one 

racial group or another may have a higher incidence rate for a 

particular disease.[Footnote 9] Not all patients with diseases that may 

be cured by stem cell transplants necessarily pursue them. Depending on 

a number of donor and patient characteristics, from about 10 to 50 

percent of patients are alive 5 years after transplants. The patients 

who do not survive may succumb either to their diseases or to the 

consequences of transplantation. Because of these low survival rates, 

some patients and physicians may be reluctant to select this stressful 

treatment under most or all circumstances. For most of the diseases 

involved, other therapies are available that may be less invasive, 

carry lower risk, or be the medically preferred initial treatment. 

Nevertheless, some of these diseases are best treated by stem cell 

transplantation, either initially or after other treatments have 

failed.



Prior to stem cell transplantation, the patient’s bone marrow and, 

consequently, immune system are destroyed with radiation or 

chemotherapy. The patient’s bloodstream is then infused with healthy 

stem cells from a donor. Healthy stem cells can be therapeutic because 

they can develop into all the components of blood, including those 

needed to replace the patient’s immune system. In an “autologous” 

transplant, these cells come from the patient’s own marrow. In a 

“syngeneic” transplant, the cells come from an identical twin. For many 

diseases, the most common type of transplant is an “allogeneic” 

transplant, which consists of stem cells from a genetically compatible 

donor.



Bone Marrow and Other Sources of Stem Cells for Transplantation:



Although bone marrow was initially the only source of stem cells for 

transplantation, in recent years two other sources of stem cells, 

umbilical cord blood and peripheral blood stem cells (PBSC), have also 

been used. In 2001, 1,215 of the transplants facilitated by NMDP (70 

percent) involved marrow, 42 (2 percent) involved cord blood, and 491 

(28 percent) involved PBSC. Umbilical cord blood is collected from the 

placenta and umbilical cord of a newborn and then preserved in a cord 

blood bank until needed by a matched patient. The number of stem cells 

typically obtained from cord blood is relatively small but is often 

adequate for pediatric patients. For transplantation from cord blood, 

the blood is volunteered when the blood is banked, not when it is used. 

The Registry began an umbilical cord blood stem cell program in 1998. 

Stem cells from peripheral blood may be obtained in numbers sufficient 

for transplantation when the donor is treated with a drug that causes 

the cells to leave the marrow and enter the bloodstream where they can 

be extracted using a process where the stems cells are removed and the 

remaining components of the blood are returned to the donor. A donor, 

matched to a patient, may be asked to donate either bone marrow or 

PBSC, depending on the preference of the patient’s physician. The 

Registry has offered PBSC to patients since 1999.



Matching Donor and Patient:



In addition to its dependence on such common determinants of treatment 

success as patient age and disease severity, the outcome of a 

transplant depends on the degree of match between donor and patient 

with respect to particular blood cell proteins--the human leukocyte 

antigens (HLA)--that are part of a person’s genetic makeup.[Footnote 

10] Each person has three primary pairs (one set of three from each 

parent) of these antigens that play a major role in the compatibility 

of a transplant. A matched donor is defined as one for whom each of 

these six antigens has the same kind of HLA. If a matched donor cannot 

be found, then a donor with certain types of mismatch may be used, 

depending on the transplant center’s preferences, although usually with 

poorer results. In general, the more closely related two people are, 

the more likely it is that their HLA will match. At one extreme, 

identical twins always match, and, in fact, match on all antigens, not 

just the six ordinarily focused upon. At the other extreme, members of 

separate racial groups are relatively unlikely to match one another. 

Full siblings can provide a six out of six match, resulting in what is 

called an “HLA-identical sibling transplant,” but only about 30 to 40 

percent of patients can be expected to have a matched sibling donor. As 

a result, unrelated donors with matched HLA are sought from the 

registries in which their HLA type has been recorded.



The definition of a match has been refined over time as scientific 

understanding of HLA increases. HLA are being typed more precisely, so 

more types of HLA can now be distinguished. Thus, some of today’s 

matches may be judged as mismatches in the future because better 

matches are possible. This increasing refinement does not mean, 

however, that finding a suitable match for transplantation is 

inevitably becoming more difficult. Some kinds of mismatch may be less 

dangerous than others. As a result, as research continues, there may be 

fewer matches by today’s standards, but relatively harmless mismatches 

will be recognized as such and used. Further, there is evidence that 

cord blood may not require as exact an HLA match as is usually sought.



The NMDP Network:



In support of the Registry, NMDP manages a worldwide network consisting 

of more than 400 donor centers, recruitment groups,[Footnote 11] 

contract laboratories where tissue is typed, apheresis 

centers,[Footnote 12] cord blood banks, collection centers where marrow 

is harvested, blood sample repositories, and transplant centers. More 

than half of these organizations are donor (91) or transplant centers 

(149). The relationship of these network components to NMDP varies. 

Some, such as the recruitment groups, were designed to be parts of the 

network and work with NMDP, whereas others, such as the transplant 

centers, exist separately from the network and function independently 

of NMDP except where specified by contract.



The NMDP network includes donor centers and other organizations in 

foreign countries.[Footnote 13] The foreign donor centers merge their 

files with the Registry, contributing more than one million donors. 

These centers are required to comply with NMDP policies, program 

standards, and other criteria, although fees for recruiting donors and 

other financial incentives and payments that go to U.S. centers are not 

paid to foreign centers.[Footnote 14] NMDP has also signed cooperative 

agreements with national registries in 13 foreign countries.[Footnote 

15] Although certain data on donors recruited into these registries are 

not entered into the Registry’s computer system, these foreign 

registries will search their donor files on behalf of a U.S. patient 

searching the Registry. In addition, 6 foreign apheresis centers, 18 

foreign bone marrow collection centers, and 36 foreign transplant 

centers are affiliated with the Registry. NMDP’s affiliations with 

foreign donor and transplant centers result in its facilitation of both 

foreign-to-U.S. and U.S.-to-foreign donations.



The existence of these international affiliations with the Registry 

does not prevent U.S. transplant centers from obtaining stem cells 

through foreign registries directly, that is, without going through 

Registry channels. Even domestically, the Registry is not a monopoly; 

other U.S. registries also maintain lists of donors, conduct searches 

for stem cells, or perform both of these functions.[Footnote 16] These 

other registries, however, are relatively small; often specialize in 

donors from particular racial or ethnic groups; and are private, with 

no national requirements.



Operation of the NMDP Registry:



The Registry serves two groups of people, donors and patients. The 

Registry’s donor centers and recruitment groups recruit donors, who are 

then managed by the donor centers. The Registry pays these centers and 

groups for signing up donors. In view of the past underrepresentation 

of minorities in the Registry, NMDP has initiated several recruitment 

efforts to increase its racial and ethnic diversity. For example, it 

provides free or low-cost minority-specific educational materials to 

donor centers and recruitment groups. Probably the most important 

aspects of managing donors are to maintain their commitment to donation 

so that they are locatable and willing to donate when their stem cells 

are requested, to keep records of how to contact them, and to drop from 

the list any individuals who are too old[Footnote 17] or no longer able 

or willing to donate.



A patient’s first contact with the Registry occurs when his or her 

physician or a transplant center conducts a free, preliminary search of 

the Registry for stem cell donors and cord blood units. The preliminary 

search, which takes about 24 hours, produces a list of donors and cord 

blood units that are potentially suitable for that patient. However, 

many patients for whom such searches are conducted are not necessarily 

good candidates for stem cell transplants. For example, some searches 

may be conducted for patients who are too sick for transplantation or 

who are good candidates for less invasive therapies.



If the physician and patient decide to continue a search for an 

unrelated donor (or unrelated cord blood) on the Registry, then more 

information about the matching stem cells is required and a formal 

search is begun. Only a physician affiliated with a transplant center 

in the NMDP network may conduct a formal search of the Registry. The 

Registry bills the transplant center a one-time activation fee of $600. 

It also bills the center for the cost of the four or five testing 

components of the search process, each of which costs more than $100. 

Since several donors may have to be tested before one is selected for 

the patient, these component charges may be made repeatedly, resulting 

in a search costing thousands of dollars to the transplant center, and 

more to the patient when the center adds its markups. Relatively few 

insurance plans pay for searches; however, plans often pay for the 

actual transplantation including the procurement of stem cells. The 

details of the formal search and the subsequent steps in the process 

possibly leading to transplantation depend on the additional 

information needed; the results of laboratory tests; and the kind of 

stem cells sought, whether stored blood from an umbilical cord or blood 

or marrow from a living donor.



If a suitable donor or suitable cord blood unit is found, and if other 

requirements in the process toward transplantation are 

fulfilled,[Footnote 18] then either (1) the marrow is harvested from 

the donor at a collection center, (2) PBSC are collected from the donor 

at an apheresis center, or (3) the cord blood is shipped from a cord 

blood bank. The stem cells are transported to the transplant center, 

often by courier. The final step is the infusing of the patient’s 

bloodstream with the selected marrow, PBSC, or cord blood. The entire 

process--from the initiation of the formal search to the transplant 

(infusion)--typically requires many months and sometimes more than 1 

year. However, some patients cannot wait this long for transplants 

because their medical conditions are deteriorating.



During the search process, NMDP offers patient advocacy services 

through two channels. Its Office of Patient Advocacy (OPA) provides 

several services, including education, support, case management 

intervention, financial assistance, and special advocacy projects. For 

example, OPA publishes the Transplant Center Access Directory, a 

patient guide listing all transplant centers in the NMDP network. The 

directory describes each center’s HLA matching criteria and lists the 

diseases each typically treats with unrelated donor marrow transplants. 

The directory also provides information on comparable search charges 

and risk-adjusted patient survival data. In addition to the services 

provided through OPA, NMDP requires that each transplant center have a 

patient advocate on staff. The patient advocate must be familiar with 

the center’s transplant program and with issues of unrelated donor stem 

cell transplantation and must not be a member of the transplant team.



OIG Review:



A 1996 OIG review raised concerns about donor center costs and 

performance. Before the review, NMDP used two methods to finance donor 

centers. NMDP paid for services at some donor centers through cost-

based contracts for direct expenses, such as labor and fringe benefits 

and donor expenses. Other donor centers received payments from NMDP for 

specified activities, such as donor recruitment and donor search 

activities. The OIG recommended that HRSA and NMDP develop a payment 

approach for all donor centers that more directly linked funding to 

performance and emphasize recruitment and retention of donors, 

particularly donors from racial and ethnic minority groups. Further, 

the OIG recommended that HRSA and NMDP develop procedures to monitor 

the performance of donor centers and other organizations in the NMDP 

network.



NMDP Has Succeeded in Increasing Recruitment of Donors, Including 

Minorities, but May Not Be Able to Equalize Access to Matches:



The program’s recruitment efforts have apparently increased the number 

of donors on the Registry since 1998 for all racial and ethnic groups, 

and the theoretical probability of finding a match has increased 

steadily over the life of the Registry. By 2001, the number of donors 

from each minority group on the Registry had grown by at least 30 

percent and was either greater than or no more than 2 percentage points 

below its representation in the general population. However, when 

viewed as a percentage of each group’s population, African Americans 

and Hispanics are still substantially underrepresented. For all racial 

and ethnic groups, the theoretical probability of finding a match has 

grown as the Registry size has increased, but equal access to a match 

may not be attainable. Differences among racial and ethnic groups in 

the rarity and variability of the genes responsible for compatibility 

in transplants may mean that the Registry cannot achieve equal 

probability for all groups. Further, the goal of equal access to a 

match conflicts to some extent with attempts to maximize the overall 

numbers of matches and transplants for the Registry.



Number of Donors on Registry Has Increased for All Groups:



The size of the Registry has increased since 1998 by 36 percent, and no 

minority group increased by less than 30 percent. NMDP’s efforts to 

recruit minorities may have substantially increased the number of 

donors from these populations. Percentage increases for minorities 

ranged from 30 percent for Native Americans to 53 percent for 

Hispanics. Caucasian donors increased 28 percent. (See table 1.) The 

multiple race category had the largest increase, 123 percent, but this 

may result in part from an increase in the use of that category by 

those to whom it applies, rather than solely from an increase in the 

availability of donors of that group.



Table 1: Percentage Increase in Registry Donors, by Racial and Ethnic 

Group, 1998 to 2000, and Current Proportion of Groups on the Registry 

and in the Population:



Race/ethnicity: African American; Number on Registry, September 30, 

1998: 264,868; Number on Registry, December 31, 2001: 363,246; 

Percentage change: 37; Percentage of donors on the Registry with known 

race[A]: 10; Percentage of U.S. population[B]: 12.



Race/ethnicity: Asian/Pacific Islander; Number on Registry, September 

30, 1998: 194,118; Number on Registry, December 31, 2001: 287,129; 

Percentage change: 48; Percentage of donors on the Registry with known 

race[A]: 8; Percentage of U.S. population[B]: 4.



Race/ethnicity: Caucasian; Number on Registry, September 30, 1998: 

1,926,675; Number on Registry, December 31, 2001: 2,460,725; Percentage 

change: 28; Percentage of donors on the Registry with known race[A]: 7; 

Percentage of U.S. population[B]: 69.



Race/ethnicity: Hispanic; Number on Registry, September 30, 1998: 

252,569; Number on Registry, December 31, 2001: 386,059; Percentage 

change: 53; Percentage of donors on the Registry with known race[A]: 

11; Percentage of U.S. population[B]: 13.



Race/ethnicity: Multiple race; Number on Registry, September 30, 1998: 

34,443; Number on Registry, December 31, 2001: 76,937; Percentage 

change: 123; Percentage of donors on the Registry with known race[A]: 

2; Percentage of U.S. population[B]: 2.



Race/ethnicity: Native American; Number on Registry, September 30, 

1998: 45,478; Number on Registry, December 31, 2001: 59,112; Percentage 

change: 30; Percentage of donors on the Registry with known race[A]: 2; 

Percentage of U.S. population[B]: 1.



Race/ethnicity: Other; Number on Registry, September 30, 1998: 13,089; 

Number on Registry, December 31, 2001: 14,142; Percentage change: 8; 

Percentage of donors on the Registry with known race[A]: 0[C]; 

Percentage of U.S. population[B]: 0[C].



Race/ethnicity: Declined to specify; Number on Registry, September 30, 

1998: 4,629; Number on Registry, December 31, 2001: 6,498; Percentage 

change: 40; Percentage of donors on the Registry with known race[A]: N/

A; Percentage of U.S. population[B]: N/A.



Race/ethnicity: Unknown[D]; Number on Registry, September 30, 1998: 

623,659; Number on Registry, December 31, 2001: 902,802; Percentage 

change: 45; Percentage of donors on the Registry with known race[A]: N/

A; Percentage of U.S. population[B]: N/A.



Race/ethnicity: Total; Number on Registry, September 30, 1998: 

3,359,528; Number on Registry, December 31, 2001: 4,556,650; Percentage 

change: 36; Percentage of donors on the Registry with known race[A]: 

100; Percentage of U.S. population[B]: 100.



Note: N/A = not applicable.



[A] As of December 31, 2001.



[B] Based on 2000 U.S. Census.



[C] Rounds to zero.



[D] Some foreign registries that are part of the NMDP network do not 

collect information on race or ethnicity.



Sources: NMDP and U.S. Bureau of the Census.



[End of table]



The total of more than 1,000,000 minority donors listed in 2001 

contrasts with the approximately 80,000 we reported in 1992. As can be 

seen in table 1, by 2001, the proportions of both African Americans and 

Hispanics on the Registry were within 2 percentage points of their 

proportions in the 2000 U.S. population. The proportions of other 

minorities on the Registry were either approximately equal to or 

exceeded their proportions in the population. While the differences 

between Registry and population levels of representation for African 

Americans and Hispanics reflect improved representation of these 

groups, the 2-percentage point differences still indicate a substantial 

underrepresentation in comparison with their proportions in the U.S. 

population. Specifically, in 1992, the proportions of African Americans 

and Hispanics, both at 4 percent of the Registry, were 8 and 5 

percentage points lower, respectively, than their proportions in the 

U.S. population (which were 12 and 9 percent, respectively). This 

translated to a 67 percent underrepresentation for African Americans 

and a 56 percent underrepresentation for Hispanics. The current 2-

percentage point differences on the Registry for these groups translate 

to a 17 percent underrepresentation for African Americans and a 15 

percent underrepresentation for Hispanics.[Footnote 19]



Theoretical Probability of Finding a Match Has Increased over Life of 

Registry:



For all racial and ethnic groups the theoretical probability of a 

patient’s finding at least one matched donor has increased every year 

since 1988 but has leveled off somewhat since 1998.[Footnote 20] The 

increase in theoretical probability represents significant progress in 

raising the likelihood of a match. It reflects inclusion in the 

Registry of the most common genetic types over the period when the 

Registry was small and new, and recruitment efforts were beginning. The 

leveling off likely reflects the fact that for all groups, after years 

of recruitment activity, improvement now occurs mainly when rare types 

are added. (See fig. 1.):



Figure 1: Theoretical Probability of Patient’s Finding at Least One 

Matched Donor, by Racial and Ethnic Group, 1988 to 2001:



[See PDF for image]



Source: NMDP.



[End of figure]



Nevertheless, the theoretical probability of finding a match varies by 

race, ranging in 2001 from under 60 percent for African Americans to 

over 80 percent for Caucasians. This probability has always been higher 

for Caucasian patients than for patients in any minority group, in 

part, perhaps, because of Caucasians’ greater numbers and level of 

representation on the Registry. The theoretical probability of finding 

a matched donor has been lowest for African American patients. This is 

because, in addition to their smaller numbers and lower level of 

representation on the Registry, their rarer and more varied HLA 

combinations make matching harder.



Equal Access for All Groups May Be Unattainable:



Because of genetic differences among racial and ethnic groups, there is 

reason to believe that patients from some minority groups, notably 

African Americans, may never have the same probability of finding 

matches, and therefore of access to transplants, as Caucasian patients, 

regardless of the efforts made to recruit them. Any patient is more 

likely to find a match in his or her own racial and ethnic group than 

in another group, so patient matching rates depend, to some extent, on 

the number of people in the patient’s group on the Registry. All 

minorities are at a disadvantage for this reason. Further, some 

minority groups, such as African Americans, are known to have more rare 

and more varied HLA combinations than do Caucasians. The likelihood of 

finding a match from among a group of racially or ethnically defined 

donors declines with the rarity and number of possible genetic types 

found among the members of that group.



In addition to these factors related to finding a match, there are 

other factors that may contribute to differences in access to a 

transplant. Some of these depend on the characteristics of those who 

volunteer for the Registry. For example, donors from different groups 

may differ in their tendency to be available (locatable, willing, and 

physically able) when called upon to actually donate. Other possible 

factors involve the attitudes, health, medical care, resources, and 

preferences of the patients. Patients of different groups may differ in 

their tendency to engage the health care system at all, to seek help 

early enough in their illnesses, or to search the Registry as opposed 

to pursuing other options. It may be possible to effect changes in 

these factors, thereby moving closer to the goal of equal opportunity 

for all racial and ethnic groups.



However, not only is the goal of equal access to transplants for all 

groups difficult to attain, but it also may conflict with the statutory 

goal of maximizing the number of patients who find a match and thereby 

maximizing the number of transplants facilitated. Recruiting donors 

with the rare HLA combinations that may be needed for minorities is 

difficult. Large numbers of donors must be recruited and retained in 

the Registry in order to identify and add each rare genetic type to the 

donor pool, so the cost of recruiting such donorsæthe incremental cost 

of adding these rare genetic types to the donor poolæis large. Thus, 

devoting many resources in pursuit of a small number of rare genetic 

types may divert resources from other efforts, such as recruiting 

Caucasians and other groups with more common genetic types, which might 

more readily increase the number of matches.



Because of the difficulty encountered in finding matches for minority 

patients, NMDP engages in a number of initiatives to increase the 

Registry’s diversity. It conducts outreach, recruitment, and 

educational efforts directed towards minorities. In addition, NMDP has 

initiated a program to pay the full costs of HLA tissue typing for 

minority donors.



Although the difficulty in finding matches for minority patients may be 

unavoidable, it may be mitigated somewhat by the efforts of the 

Registry to increase the number of donors on whom it has complete HLA 

typing. The vast majority of actual donations are obtained from by 

donors whose HLA is fully typed.[Footnote 21] When only these donors 

are considered, each minority constitutes a larger portion of the 

Registry than its representation in the population. Therefore, because 

access to a match depends upon, for the most part, the fully typed 

donors on the Registry, access for minorities may be somewhat better 

than might be assumed by looking at the Registry as a whole.



National Registry May Be Underutilized:



Although the exact number of patients in need of transplants from 

unrelated donors is not known, the number of patients utilizing the 

Registry to search for matches is about one-third of the estimated 

number of patients in need of unrelated donor transplants. About one-

tenth of the number of patients estimated to be in need of unrelated 

donor transplants obtain transplants facilitated by NMDP. These figures 

suggest that the Registry may be underutilized for both searching and 

facilitating transplants.[Footnote 22] Physicians for approximately 

15,000 U.S. patients requested preliminary searches of the Registry 

from 1997 through 2000. This number represents 34 percent of the 44,740 

U.S. patients estimated to be in need of stem cell transplants from 

unrelated donors in that 4-year period. About 4,000, or 27 percent, of 

the patients whose physicians searched the Registry eventually received 

transplants facilitated by NMDP. However, a significant proportion of 

searches were not completed because stem cells were obtained from 

donors or organizations without the involvement of NMDP.



Estimates Suggest about One-Third of Patients in Need Search the 

Registry and about One-Tenth Receive Transplants 

:



From 1997 through 2000, physicians carried out preliminary searches for 

34 percent of the number of U.S. patients estimated to be in need of 

transplantation from unrelated donors at any time during that period. 

The number of transplants facilitated by NMDP for all U.S. patients was 

9 percent of the number estimated to be in need. The precise number of 

patients in need of unrelated donor transplants is not known. However, 

there is a greater than 10 to 1 ratio between the number of such 

patients estimated to be in need and the number of transplants 

facilitated by NMDP. This suggests that the Registry may be 

underutilized, as many more U.S. patients may need unrelated donor 

transplants than obtain them through the Registry.[Footnote 23] The 

ratio of the number of preliminary searches to the number of patients 

in need varied by race and ethnicity. Among specific racial and ethnic 

groups, the percentage of preliminary searches was highest for 

Caucasian patients (35 percent), and was lowest for Hispanic patients 

(24 percent) and Native American patients (24 percent). (See table 2.) 

We do not know why these apparent disparities in search rates exist.



Table 2: U.S. Patients’ Utilization of the Registry, by Race and 

Ethnicity, 1997 to 2000:



Race/ethnicity: African American; Estimated number of patients without 

matched sibling donor[A] 

(patients in need): 5,397; Actual number of preliminary searches: 

1,694; Ratio of number of preliminary searches to number of patients in 

need: 0.31; Actual number (percentage) of preliminary searches 

resulting in formal searches: 958 (57); Actual number (percentage) of 

preliminary searches resulting in NMDP-facilitated transplants: 256 

(15); Ratio of number of NMDP-facilitated transplants to number of 

patients in need: 0.05.



Race/ethnicity: Asian/Pacific Islander; Estimated number of patients 

without matched sibling donor[A] 

(patients in need): 1,666; Actual number of preliminary searches: 439; 

Ratio of number of preliminary searches to number of patients in need: 

0.26; Actual number (percentage) of preliminary searches resulting in 

formal searches: 270 (62); Actual number (percentage) of preliminary 

searches resulting in NMDP-facilitated transplants: 96 (22); Ratio of 

number of NMDP-facilitated transplants to number of patients in need: 

0.06.



Race/ethnicity: Caucasian; Estimated number of patients without matched 

sibling donor[A] 

(patients in need): 30,929; Actual number of preliminary searches: 

10,844; Ratio of number of preliminary searches to number of patients 

in need: 0.35; Actual number (percentage) of preliminary searches 

resulting in formal searches: 7,079 (65); Actual number (percentage) of 

preliminary searches resulting in NMDP-facilitated transplants: 3,321 

(31); Ratio of number of NMDP-facilitated transplants to number of 

patients in need: 0.11.



Race/ethnicity: Hispanic; Estimated number of patients without matched 

sibling donor[A] 

(patients in need): 5,613; Actual number of preliminary searches: 

1,366; Ratio of number of preliminary searches to number of patients in 

need: 0.24; Actual number (percentage) of preliminary searches 

resulting in formal searches: 840 (61); Actual number (percentage) of 

preliminary searches resulting in NMDP-facilitated transplants: 317 

(23); Ratio of number of NMDP-facilitated transplants to number of 

patients in need: 0.06.



Race/ethnicity: Native American; Estimated number of patients without 

matched sibling donor[A] 

(patients in need): 329; Actual number of preliminary searches: 80; 

Ratio of number of preliminary searches to number of patients in need: 

0.24; Actual number (percentage) of preliminary searches resulting in 

formal searches: 56 (70); Actual number (percentage) of preliminary 

searches resulting in NMDP-facilitated transplants: 20 (25); Ratio of 

number of NMDP-facilitated transplants to number of patients in need: 

0.06.



Race/ethnicity: Other; Estimated number of patients without matched 

sibling donor[A] 

(patients in need): 806; Actual number of preliminary searches: 365; 

Ratio of number of preliminary searches to number of patients in need: 

0.45; Actual number (percentage) of preliminary searches resulting in 

formal searches: 213 (58); Actual number (percentage) of preliminary 

searches resulting in NMDP-facilitated transplants: 39 (11); Ratio of 

number of NMDP-facilitated transplants to number of patients in need: 

0.05.



Race/ethnicity: Total; Estimated number of patients without matched 

sibling donor[A] 

(patients in need): 44,740; Actual number of preliminary searches: 

15,231[B]; Ratio of number of preliminary searches to number of 

patients in need: 0.34; Actual number (percentage) of preliminary 

searches resulting in formal searches: 9,623c (63); Actual number 

(percentage) of preliminary searches resulting in NMDP-facilitated 

transplants: 4,056[D] (27); Ratio of number of NMDP-facilitated 

transplants to number of patients in need: 0.09.





AFor Caucasians, the number of HLA-identical sibling transplants 

multiplied by the number of patients expected to be without matched 

sibling donors for each such transplant was derived from data obtained 

from the Statistical Center of the IBMTR and Autologous Blood and 

Marrow Transplant Registry (ABMTR). (The analysis has not been reviewed 

or approved by the Advisory Committees of the IBMTR and ABMTR.) See 

appendix I for a description of this method of estimation. For each of 

the other groups, the number was derived by assuming that the group’s 

need is the same as it is for Caucasians and in proportion to the 

group’s representation in the U.S. population.



[B] Includes 443 preliminary searches, not included elsewhere in the 

column, from patients of unknown race/ethnicity.



[C] Includes 207 formal searches, not included elsewhere in the column, 

from patients of unknown race/ethnicity.



[D] Includes 7 transplants, not included elsewhere in the column, from 

patients of unknown race/ethnicity.



Source: GAO analysis of data from the Statistical Center of the IBMTR 

and ABMTR and NMDP.



[End of table]



About one-fifth of the number of patients estimated to be in need 

formally searched the Registry (9,623 out of 44,740). Less than one-

tenth of those estimated to be in need ultimately received NMDP-

facilitated transplants. The numbers and percentages of preliminary 

searches that progressed to formal searches from 1997 through 2000 are 

presented by racial and ethnic group in table 2. The overall rate of 

progression from preliminary to formal search is 63 percent. Further, 

4,056 of the 15,231 U.S. patients (27 percent) for whom preliminary 

searches were conducted from 1997 through 2000 eventually received 

NMDP-facilitated transplants. This number corresponds to 9 percent of 

the number of patients estimated to be in need of unrelated transplants 

during that period.



Reasons for Cancellation Vary and Include Obtaining Stem Cells from a 

Provider Other than NMDP:



Reasons for cancellation of preliminary searches or formal searches 

vary. Although clinical reasons, such as a change in medical condition, 

are the most commonly cited explanations for cancellation of both 

preliminary and formal searches,[Footnote 24] another relatively 

frequent reason is that stem cells are obtained from a provider other 

than NMDP, such as a related donor or another registry. (See tables 3 

and 4.) We do not know the proportion of these cases that used a 

related donor, and some cases may not have been able to find a 

potential match at NMDP. However, it is likely that in at least some of 

these cases, NMDP might have facilitated a transplant if the patient’s 

transplant center had not selected another registry to provide the stem 

cells, thus representing another kind of possible underutilization of 

NMDP. Lack of donor availability--not finding any potential matches--

and financial reasons are not commonly cited as reasons for 

cancellation of either kind of search, although it is possible that 

patients with limited financial resources or insurance may not be 

encouraged to make preliminary searches.



Table 3: Reasons for Preliminary Search Cancellation, January 2000 

through September 2001:



Reason for cancellation: No donor available; Number of preliminary 

search cancellations: 105; Percentage of preliminary search 

cancellations: 7.



Reason for cancellation: Another provider; Number of preliminary search 

cancellations: 317; Percentage of preliminary search cancellations: 20.



Reason for cancellation: Patient stable; Number of preliminary search 

cancellations: 383; Percentage of preliminary search cancellations: 25.



Reason for cancellation: Financial reasons; Number of preliminary 

search cancellations: 114; Percentage of preliminary search 

cancellations: 7.



Reason for cancellation: Personal reasons[A]; Number of preliminary 

search cancellations: 187; Percentage of preliminary search 

cancellations: 12.



Reason for cancellation: Deterioration/death; Number of preliminary 

search cancellations: 160; Percentage of preliminary search 

cancellations: 10.



Reason for cancellation: Other; Number of preliminary search 

cancellations: 284; Percentage of preliminary search cancellations: 18.



Reason for cancellation: Total; Number of preliminary search 

cancellations: 1,550; Percentage of preliminary search cancellations: 

100.





Note: These data are based on a survey, conducted by OPA, of 

individuals making preliminary searches.



[A] Personal reasons for preliminary search cancellations include 

decisions made by physicians and patients.



Source: NMDP.



[End of table]



Table 4: Reasons for Formal Search Cancellation, 1997 to 2000:



Reason for cancellation: No donor available; Number of formal search 

cancellations: 131; Percentage of formal search cancellations: 3.



Reason for cancellation: Another provider; Number of formal search 

cancellations: 1,200; Percentage of formal search cancellations: 25.



Reason for cancellation: Financial reasons; Number of formal search 

cancellations: 22; Percentage of formal search cancellations: 0.



Reason for cancellation: Personal reasons[A]; Number of formal search 

cancellations: 733; Percentage of formal search cancellations: 15.



Reason for cancellation: Deterioration/death; Number of formal search 

cancellations: 2,096; Percentage of formal search cancellations: 44.



Reason for cancellation: Alternative therapy; Number of formal search 

cancellations: 357; Percentage of formal search cancellations: 7.



Reason for cancellation: Other; Number of formal search cancellations: 

262; Percentage of formal search cancellations: 5.



Reason for cancellation: Total; Number of formal search cancellations: 

4,801; Percentage of formal search cancellations: 100.





APersonal reasons for formal search cancellations include decisions 

made by physicians, patients and patients’ families.



Source: NMDP.



[End of table]



Several factors may influence a decision to obtain stem cells from a 

provider outside the NMDP network, including the source of stem cells 

preferred by the physician, the costs involved, and the timeliness of 

the response. Outside providers may need to be used when the physician 

sees cord blood as a viable alternative source to bone marrow or PBSC 

because some cord blood banks do not list their cord blood units with 

NMDP.[Footnote 25]



Search and procurement costs can also be a factor. Administrators of 

transplant centers that have done non-NMDP-affiliated transplants told 

us that other registries charge less for searches than NMDP does. For 

example, we were told that only a few other registries worldwide charge 

a search activation fee in addition to their charges for the specific 

medical procedures needed to confirm that a particular donor is healthy 

and matched to the patient. In addition, the cost of stem cell 

procurement at NMDP tends to be higher. One transplant center director 

told us that the center pays about $13,000 for stem cells obtained 

directly from overseas registries and about $21,000 for NMDP stem 

cells. However, even when NMDP is not paid for a formal search or for 

stem cells, it may still have been utilized. An official at NMDP 

informed us that it is possible for a transplant center to determine 

the NMDP-affiliated registry at which a foreign (but not domestic) 

potential match is registered on the basis of a preliminary search and 

to contact the foreign registry directly to obtain the stem cells. 

Moreover, that official stated that some transplant centers may do this 

regularly. Thus, although NMDP may not be recorded as having 

facilitated the transplants that result, its role in helping to locate 

donors in such cases means that its utilization is somewhat greater 

than the record suggests.



Timeliness can be another factor. A few center administrators mentioned 

that NMDP takes longer to provide stem cells than do other registries. 

For example, one administrator told us that the time it takes to obtain 

a donor sample for testing at the transplant center--an important 

component of the overall search process--can be a week longer for NMDP 

than for a foreign registry, depending on whether NMDP judges the 

search to be urgent. Waiting this additional week can be frustrating 

for those at the transplant center who are anxious to determine whether 

they have a confirmed match or will have to continue searching. Another 

director told us that stem cells from non-NMDP providers are more 

likely to be received by the date the transplant center requests them 

than are stem cells from NMDP. NMDP has attempted to shorten its time 

from formal search initiation to transplant and reports that its median 

time has decreased from 4.8 months from 1992 through 1993 to 3.7 months 

in 2000. The optimal time frames for patients vary. Some may not be 

urgent, but NMDP has shown that it is possible to complete urgent 

searches in less than a month and reports that it expects to begin 

offering urgent searches as an option to transplant centers.



Organizations in the NMDP Network Generally Comply with Its Standards 

and Procedures:



Organizations that participate in the NMDP network generally comply 

with the standards and procedures it has established. In order to 

encourage adherence, NMDP uses various mechanisms to monitor compliance 

and performance. These include site visits, the Continuous Process 

Improvement (CPI) program, and incident reports, as well as a financial 

incentive system designed to improve the performance of donor centers. 

The results of the selected site visits, analysis of CPI measures, and 

incident report summaries we reviewed show that the organizations in 

the NMDP network generally adhere to NMDP’s standards and procedures. 

In general, NMDP ensures compliance by taking action against 

noncompliant organizations. (See app. II for examples of how NMDP uses 

these systems to achieve compliance with respect to selected 

activities.) In 2001, NMDP required 24 donor and transplant centers to 

take corrective actions because they did not meet its standards. The 

incentive system encourages compliance by linking donor center 

reimbursement to performance.



NMDP Monitors Network Compliance and Performance:



NMDP uses several mechanisms to encourage the compliance and 

performance of the participating organizations in its network. NMDP 

staff members conduct site visits to donor centers to monitor the 

centers’ compliance with NMDP’s standards and procedures and to provide 

feedback about the results. It also employs the CPI program to assess 

and provide feedback at donor, transplant, and bone marrow collection 

centers. Further, NMDP monitors incident reports from donor, 

transplant, and collection centers and may take corrective action 

including, in serious cases, suspension or termination.



According to NMDP officials, NMDP staff members conduct site visits at 

donor centers approximately every 2 years to assess donor center 

compliance with program standards and procedures. NMDP staff members 

review the organization of the program (such as its support and 

staffing structure), recruitment activities (such as performance 

against goals and donor drive compliance), donor management activities 

(such as management of patient-related donor search requests, 

confidentiality procedures, and records management), and billing and 

reimbursement to determine adherence to NMDP’s standards and 

procedures. They also compare performance against goals for various 

recruitment activities. Upon completion of these visits, NMDP staff 

members discuss the results with the center staff and provide a summary 

report. Centers that are noncompliant are advised of the problems and 

are required to submit corrective action plans to NMDP that address the 

problems. Our review of donor center site visit reports indicates that 

the reports identified problems and the corrective actions required of 

the centers to meet NMDP criteria.



Since 1998, NMDP has conducted additional site visits at transplant 

centers to verify the accuracy of the data that the transplant centers 

submit electronically to NMDP. NMDP staff members compare the data from 

the centers’ records with the data from NMDP’s computer system. During 

these visits, NMDP staff members may also review other activities, such 

as the signing of patient consent forms. The site visits are scheduled 

for each transplant center every 4 years. NMDP plans to issue its first 

annual report on the results of the first cycle of site visits in 

September 2002.



NMDP monitors the operations and performance of its centers through the 

CPI program. The program includes nine goals to increase the efficiency 

of key activities in the search and donation process and measures 

performance against these goals. For example, at donor centers, NMDP 

measures the timeliness of registering new donors, resolving search-

related requests, and processing requests for HLA blood typing. At 

transplant centers, NMDP measures the time it takes to resolve and 

report confirmatory testing results. NMDP also monitors post-transplant 

data submission through CPI. These outcome data are used in research 

studies to analyze outcomes for donors and patients. NMDP also monitors 

the accuracy and timeliness with which donor and transplant centers 

submit donor and patient blood samples to NMDP’s research repository. 

NMDP provides regular feedback to donor and transplant centers 

concerning their performance on CPI measures. For example, each center 

receives a monthly report summarizing the results of its activities, 

along with those of all other centers, in the previous month. The 

reports allow centers to analyze how consistently they perform and to 

compare their results to those of other centers in the network. NMDP 

also conducts a year-end analysis to provide feedback to centers.



Through its CPI program, NMDP monitors whether organizations in its 

network meet goals for timeliness and may recommend corrective actions 

for centers that do not meet these goals.[Footnote 26] A year-end 

analysis of the CPI program shows that during 2001 almost half (44 of 

91) of donor centers met all nine CPI goals for the search process. In 

addition, 20 more donor centers met eight of nine goals, and 9 others 

met seven of nine goals. According to NMDP, the remaining 18 donor 

centers (20 percent) that met six or fewer goals were the focus of 

technical assistance to improve their performance. Our analysis shows 

that 5 of the 91 donor centers (5 percent) were placed on review or 

probation for failing to meet CPI goals in 2001.



Our analysis also shows that NMDP placed 18 of the 129 transplant 

centers (14 percent) on probation. Eight of these were placed on 

probation for failure to meet CPI goals for the search process, seven 

for failure to meet CPI measures concerned with timely submission of 

recipient follow-up information, and three for problems related to the 

accuracy and timeliness of submissions of donor and patient research 

blood samples.



NMDP supplements these activities with incident reports, which are 

written accounts of deviations from policies and standards that are 

categorized by the nature of a deviation and include, but are not 

limited to, categories such as confidentiality concerns, customer 

service, and product transport. NMDP uses incident reports to track 

deviations from its standards by recording the specifics of incidents. 

NMDP staff members follow up and investigate incidents. In addition, an 

NMDP committee reviews a summary report of incidents twice a year to 

identify developing trends that may affect an individual center or the 

entire network. Since NMDP reviews center participation annually, the 

committee may follow up on deviations from NMDP’s standards or take 

action such as probation, suspension, or termination during the 

reapplication process. We reviewed a summary of incidents categorized 

by type of problem and the corrective actions taken to resolve them. 

For example, one incident involved an operating room staff member 

administering less appropriate blood, rather than the donor’s own 

blood, which was available for that purpose, during a marrow harvest. 

NMDP monitored an investigation at the hospital to ensure that the 

problem would be addressed.



Donor Center Reimbursement Is Linked to Performance:



To improve the operation of its donor centers, NMDP ties their 

reimbursement to their performance. In 1997, NMDP instituted a new 

reimbursement system that links payment to performance on CPI goals for 

all donor centers.[Footnote 27] NMDP pays donor centers a fee for each 

activity to recruit donors for the Registry, such as signing up donors, 

typing their tissues, maintaining their files, and other activities 

related to confirming that the donors identified as potential matches 

for a searching patient actually match and are medically cleared for 

donation. NMDP pays each donor center a recruitment fee of $28 and $10 

for every minority and Caucasian donor, respectively, recruited up to 

the number specified in its recruitment goal. NMDP establishes annual 

recruitment goals for each donor center based on the demographics of 

the local population. When donors are recruited, the donor centers that 

do not register a specific percentage of the new donors within a 

certain period incur financial penalties. For example, the CPI goal for 

registering new donors is to register at least 85 percent of them 

within 35 days of the date on which they volunteer. NMDP would reduce 

the total recruitment fee it pays to donor centers that register less 

than 85 percent of new donors within this time frame. NMDP data show 

that in May 2001, 98 percent of all donor centers met this goal. In 

addition, NMDP pays incentives to donor centers for retaining donors at 

various points in the donation process.



Concluding Observations:



In spite of progress in recruiting minority donors, racial and ethnic 

disparities in the Registry remain, due in part to differences in the 

genetic variability within groups. Thus, differences among racial and 

ethnic groups in the probability of obtaining transplants will likely 

continue. Many in need of transplants may not search the Registry; 

those that do often do not obtain them, and for those that obtain them, 

the transplants may not be facilitated by NMDP. Although NMDP enhances 

the quality of its network by actively monitoring the compliance and 

performance of the component organizations, it has not attained the 

level of utilization that might be expected.



Agency Comments:



In its written comments on a draft of this report, HRSA stated that the 

report provides an accurate and helpful overview of the status of the 

National Bone Marrow Donor Registry. HRSA agreed that recruitment of 

donors cannot be the sole strategy for improving access to unrelated 

donor transplants for minority patients or those with unusual antigens, 

and cited the need for other efforts to supplement recruitment 

activities. However, HRSA noted that the Registry consists of two 

distinct groups of donors, those who are fully HLA typed and those who 

are less than fully typed. Since the vast majority of actual donors are 

selected from the fully typed portion, minority racial and ethnic 

groups therefore make up a larger proportion of the Registry than their 

representation in the U.S. population. We have noted in the report 

that, because of this, access for minorities may be somewhat better 

than might be assumed by looking at the Registry as a whole.



With regard to underutilization of the Registry, HRSA agreed that many 

patients who could benefit from unrelated donor transplants never 

consult the Registry or do so too late in the course of their 

illnesses. HRSA suggested a slightly modified method for estimating the 

number of patients in need. We modified table 2 in accordance with its 

suggestions, but note that both approaches produce virtually identical 

estimates of overall utilization. (See app. I.):



Finally, HRSA noted that many factors affect the time required to 

complete a search of the Registry. While searches frequently take many 

months and the median search time has decreased, NMDP has completed 

medically urgent searches in less than a month, on a pilot basis, and 

reports that it expects to begin offering urgent searches as an option 

to transplant centers. We have revised the report to include this 

clarification. HRSA also provided technical comments, which we 

incorporated as appropriate. HRSA’s comments are reprinted in appendix 

III.



We are sending this report to the Administrator of HRSA, the NMDP Chief 

Executive Officer, and other interested persons. We will also make 

copies available to others upon request. In addition, the report will 

be available at no charge on the GAO Web site at http://www.gao.gov.



If you or your staff members have any questions about this report, 

please call me at (202) 512-7119. Key contributors to this assignment 

are listed in appendix IV.



Janet Heinrich

Director, Health Care--Public Health Issues:



List of Committees:



The Honorable Robert C. Byrd

Chairman

The Honorable Ted Stevens

Ranking Minority Member

Committee on Appropriations

United States Senate:



The Honorable Edward M. Kennedy

Chairman

The Honorable Judd Gregg

Ranking Minority Member

Committee on Health, Education,

 Labor, and Pensions

United States Senate:



The Honorable C.W. Bill Young

Chairman

The Honorable David Obey

Ranking Minority Member

Committee on Appropriations

House of Representatives:



The Honorable W.J. “Billy” Tauzin

Chairman

The Honorable John D. Dingell

Ranking Minority Member

Committee on Energy and Commerce

House of Representatives:



[End of section]



Appendix I Methods of Assessing Registry Utilization:



Registry utilization is the extent to which patients in need of 

unrelated stem cell transplants search the Registry or obtain NMDP-

facilitated transplants. In determining utilization, it is necessary to 

use indirect methods to calculate the number of patients in need 

because it is impossible to determine this number directly. For 

example, although we may be able to obtain data on the number of 

patients who have been diagnosed with certain blood and immune system 

diseases, we are unable to determine the number for whom stem cell 

transplants are the best treatment.



One measure of the utilization of the Registry is the extent to which 

the number of patients obtaining transplants facilitated by the 

Registry is as high as it could be. The maximum possible utilization of 

the Registry would be indicated if the number of U.S. patients 

conducting preliminary searches was approximately equal to the 

estimated number of patients needing unrelated donor transplants. A 

second measure of utilization is the extent to which patients search 

the Registry.



The method we used to assess the two aspects of utilization--searching 

the Registry and obtaining an NMDP-facilitated transplant--is also used 

by NMDP. It involves estimating the number of patients in need of 

unrelated donor transplants by using data on the number of HLA-

identical sibling transplants obtained from IBMTR.[Footnote 28] This 

method and two alternative methods that are also used by NMDP to assess 

utilization by U.S. patients, one based on the number of preliminary 

searches conducted and the other based on the incidence of disease, are 

described here.



Method Based on Number of HLA-Identical Sibling Transplants:



For the years from 1997 through 2000, we estimated the number of 

Caucasian patients in need of unrelated donor transplants based on the 

average annual number of Caucasian HLA-identical sibling transplants 

performed during those years. To obtain this estimate, we multiplied 

the number of HLA-identical sibling transplants, for Caucasians, by the 

number of patients of that group that genetic theory predicts--on the 

basis of the average number of children born to the women of that 

group--are in need of unrelated donor transplants for every Caucasian 

HLA-identical sibling transplant in the United States.



The average number of children born to Caucasian women over a lifetime 

during the years from 1989 through 1995 was 1.7925.[Footnote 29] 

Subtracting the individual who is in need of a transplant gives n = 

0.7925 as the number of siblings available to be transplant donors. The 

likelihood of a match between two siblings is 25 percent because each 

child inherits one-half of each parent’s HLA genes, resulting in a one 

out of four chance of having the same HLA genes as a sibling has. 

Therefore, the probability that no sibling HLA identically matches the 

one in need is P = (0.75)N . For a Caucasian patient, P = (0.75)0.7925 

= 0.796134.



The number of patients in need of unrelated stem cell transplants is 

equal to the number of sibling donor transplants multiplied by P/(1 - 

P). Therefore, for every HLA-identical sibling transplant recorded for 

a Caucasian patient, there will be 0.796134/(1 - 0.796134) = 3.90518 

patients in need of unrelated donor transplants. Because there were 

7,920 sibling transplants performed for Caucasian patients from 1997 

through 2000, we estimate that 3.90518(7,920) = 30,929 Caucasian 

patients were in need of stem cell transplants during that period. The 

estimates for other racial and ethnic groups are presented in table 2. 

Because minorities generally have less access to health care[Footnote 

30] and may therefore have less access to sibling transplants 

specifically, these estimates were obtained by assuming that each 

minority group’s need for unrelated donor transplants is proportional 

to the Caucasian group’s need. The estimates were obtained by 

multiplying the number of persons in the minority group by the 

proportion of Caucasians in need of unrelated donor transplants. This 

approach implicitly assumes that differences across groups in fertility 

rates are of negligible importance in computing the numbers of patients 

in need of unrelated donor transplants.



An alternative approach assumes that minorities and Caucasians have 

equal access to HLA-identical sibling transplants. Based on this 

assumption, this approach derives the needs of minorities for unrelated 

donor transplants directly from their observed numbers of HLA-identical 

sibling transplants. In doing so, it allows for the possibility that 

each group has its own disease incidence rates and that the differences 

among groups in their relative levels of sibling donations reflect 

these rates, not differences in access. (See table 5.) This approach, 

while utilizing somewhat different assumptions from the method above, 

produces a virtually identical estimate of the underutilization of the 

Registry (10 percent versus 9 percent).



Table 5: Alternate Approach to the Analysis of U.S. Patients’ 

Utilization of the Registry, by Race and Ethnicity, 1997 to 2000:



Race/ethnicity: African American; Estimated number of patients without 

matched sibling donor[A,B] 

(patients in need): 1,880; Actual number of preliminary searches: 

1,694; Ratio of number of preliminary searches to number of patients in 

need: 0.90; Actual number (percentage) of preliminary searches 

resulting in formal searches: 958 (57); Actual number (percentage) of 

preliminary searches resulting in NMDP-facilitated transplants: 256 

(15); Ratio of number of NMDP-facilitated transplants to number of 

patients in need: 0.14.



Race/ethnicity: Asian/Pacific Islander; Estimated number of patients 

without matched sibling donor[A,B] 

(patients in need): 1,355; Actual number of preliminary searches: 439; 

Ratio of number of preliminary searches to number of patients in need: 

0.32; Actual number (percentage) of preliminary searches resulting in 

formal searches: 270 (62); Actual number (percentage) of preliminary 

searches resulting in NMDP-facilitated transplants: 96 (22); Ratio of 

number of NMDP-facilitated transplants to number of patients in need: 

0.07.



Race/ethnicity: Caucasian; Estimated number of patients without matched 

sibling donor[A,B] 

(patients in need): 35,964; Actual number of preliminary searches: 

10,844; Ratio of number of preliminary searches to number of patients 

in need: 0.30; Actual number (percentage) of preliminary searches 

resulting in formal searches: 7,079 (65); Actual number (percentage) of 

preliminary searches resulting in NMDP-facilitated transplants: 3,321 

(31); Ratio of number of NMDP-facilitated transplants to number of 

patients in need: 0.09.



Race/ethnicity: Hispanic; Estimated number of patients without matched 

sibling donor[A,B] 

(patients in need): 1,593; Actual number of preliminary searches: 

1,366; Ratio of number of preliminary searches to number of patients in 

need: 0.86; Actual number (percentage) of preliminary searches 

resulting in formal searches: 840 (61); Actual number (percentage) of 

preliminary searches resulting in NMDP-facilitated transplants: 317 

(23); Ratio of number of NMDP-facilitated transplants to number of 

patients in need: 0.20.



Race/ethnicity: Native American; Estimated number of patients without 

matched sibling donor[A,B] 

(patients in need): 97; Actual number of preliminary searches: 80; 

Ratio of number of preliminary searches to number of patients in need: 

0.82; Actual number (percentage) of preliminary searches resulting in 

formal searches: 56 (70); Actual number (percentage) of preliminary 

searches resulting in NMDP-facilitated transplants: 20 (25); Ratio of 

number of NMDP-facilitated transplants to number of patients in need: 

0.21.



Race/ethnicity: Other; Estimated number of patients without matched 

sibling donor[A,B] 

(patients in need): 290; Actual number of preliminary searches: 365; 

Ratio of number of preliminary searches to number of patients in need: 

1.26; Actual number (percentage) of preliminary searches resulting in 

formal searches: 213 (58); Actual number (percentage) of preliminary 

searches resulting in NMDP-facilitated transplants: 39 (11); Ratio of 

number of NMDP-facilitated transplants to number of patients in need: 

0.13.



Race/ethnicity: Total; Estimated number of patients without matched 

sibling donor[A,B] 

(patients in need): 41,179; Actual number of preliminary searches: 

15,231[C]; Ratio of number of preliminary searches to number of 

patients in need: 0.37; Actual number (percentage) of preliminary 

searches resulting in formal searches: 9,623 (63); Actual number 

(percentage) of preliminary searches resulting in NMDP-facilitated 

transplants: 4,056 (27); Ratio of number of NMDP-facilitated 

transplants to number of patients in need: 0.10.





Note: This table presents an alternate approach to that given in table 

2.



[A] Number of HLA-identical sibling transplants multiplied by the 

number of patients expected to be without matched sibling donors for 

each such transplant was derived from data obtained from the 

Statistical Center of the IBMTR and Autologous Blood and Marrow 

Transplant Registry (ABMTR). (The analysis has not been reviewed or 

approved by the Advisory Committees of the IBMTR and ABMTR.):



[B] Numbers based on the HLA-identical sibling transplants of the 

designated race/ethnicity plus a portion of those of unknown race/

ethnicity. These unknowns submitted record forms that did not ask about 

race/ethnicity. The unknowns can be assumed to be similar in racial/

ethnic distribution to the other patients, and so we distributed them 

among the racial/ethnic groups according to that distribution. It can 

therefore be assumed that there is no racial bias in this estimation 

method.



[C] Includes 443 preliminary searches, not included elsewhere in the 

column, from patients of unknown race/ethnicity.



Source: GAO analysis of data from the Statistical Center of the IBMTR 

and ABMTR and NMDP.



[End of table]



Method Based on Number of Preliminary Searches:



The second method used by NMDP to assess Registry utilization is based 

simply on the annual number of patients conducting preliminary 

searches. In order to use this method, one must assume that this number 

directly represents those in need of unrelated donor transplants. One 

cannot assess the extent to which those in need search the Registry on 

the basis of this number since the number itself is the number of 

patients searching. However, one can assess the extent to which those 

in need obtain NMDP-facilitated transplants by considering the annual 

percentage of patient searches that result in NMDP-facilitated 

transplants. This method yields an estimate of the patients searching 

who obtain NMDP-facilitated transplants of 27 percent. (See table 5.):



Although this approach has been used by NMDP as a way of assessing 

utilization, officials at NMDP observe that the validity of this 

approach to utilization assessment is limited by the freedom with which 

patients can choose whether to search. These officials point out that 

preliminary searches are performed for some patients who are not good 

candidates for transplant and that other patients who should submit 

preliminary searches probably do not. Because of the lack of 

correspondence between the number of patients in need and the number 

performing preliminary searches, this estimate is not likely to be as 

accurate as the other two.



Method Based on Incidence of Disease:



The third method used by NMDP is based on an estimate of the annual 

number of U.S. patients newly diagnosed from 1997 through 2000 with 

selected diseases that might benefit from unrelated stem cell 

transplants.[Footnote 31] The estimated number of potential recipients 

for each disease is obtained from disease incidence estimates, with 

adjustments for the likelihood that (1) the patient is young enough to 

benefit from transplantation, (2) disease severity is not so great as 

to make transplantation futile, and (3) an HLA-identical sibling donor 

is available, thereby making unrelated donor transplant unnecessary. 

The ratio of the annual number of NMDP-facilitated transplants for U.S. 

patients diagnosed with these selected diseases during this period to 

the estimated number of new U.S. patients with the diseases is used to 

assess utilization.[Footnote 32] (See table 6.) The ratio, for all 

patients with the selected diseases, corresponds to an estimated 

percentage of candidates obtaining transplants--10 percent--that is 

very close to the estimate obtained by the first method. The validity 

of this third method is constrained by the limited number of diseases 

for which data are available.



Table 6: Average Annual Unrelated Donor NMDP-Facilitated Transplants 

and Estimated Number of Potential Recipients for U.S. Patients with 

Selected Diseases Who Might Benefit from Unrelated Stem Cell 

Transplants, by Race/Ethnicity, 1997 through 2000:



Race/ethnicity: African American; Acute lymphocytic leukemia: 8; Acute 

myelogenous leukemia: 12; Chronic myelogenous leukemia: 18; Non-

Hodgkin’s lymphoma: 4; Total: 42.



Race/ethnicity: Caucasian; Acute lymphocytic leukemia: 121; Acute 

myelogenous leukemia: 197; Chronic myelogenous leukemia: 161; Non-

Hodgkin’s lymphoma: 68; Total: 547.



Race/ethnicity: Hispanic; Acute lymphocytic leukemia: 24; Acute 

myelogenous leukemia: 12; Chronic myelogenous leukemia: 14; Non-

Hodgkin’s lymphoma: 2; Total: 52.



Race/ethnicity: Native American; Acute lymphocytic leukemia: 1; Acute 

myelogenous leukemia: 1; Chronic myelogenous leukemia: 1; Non-Hodgkin’s 

lymphoma: 0; Total: 3.



Race/ethnicity: Asian/Pacific Islander; Acute lymphocytic leukemia: 6; 

Acute myelogenous leukemia: 5; Chronic myelogenous leukemia: 4; Non-

Hodgkin’s lymphoma: 1; Total: 16.



Race/ethnicity: Other; Acute lymphocytic leukemia: 2; Acute myelogenous 

leukemia: 1; Chronic myelogenous leukemia: 2; Non-Hodgkin’s lymphoma: 

0; Total: 5.



Race/ethnicity: Total number of NMDP-facilitated transplants; Acute 

lymphocytic leukemia: 162; Acute myelogenous leukemia: 228; Chronic 

myelogenous leukemia: 200; Non-Hodgkin’s lymphoma: 75; Total: 665.



Race/ethnicity: Estimated number of new U.S. patients with selected 

diseases who might benefit from unrelated stem cell transplants; Acute 

lymphocytic leukemia: 1,359; Acute myelogenous leukemia: 662; Chronic 

myelogenous leukemia: 761; Non-Hodgkin’s lymphoma: 4,081; Total: 6,863.



Race/ethnicity: Percentage of new patients who receive NMDP-facilitated 

transplants; Acute lymphocytic leukemia: 12; Acute myelogenous 

leukemia: 34; Chronic myelogenous leukemia: 26; Non-Hodgkin’s lymphoma: 

2; Total: 10.





Sources: GAO analysis of data from NMDP and the National Cancer 

Institute’s Surveillance, Epidemiology, and End Results program.



[End of table]



[End of section]



Appendix II How NMDP Achieves Network Compliance with Selected 

Standards and Procedures:



NMDP requires that the organizations participating in its network 

comply with its standards and procedures. This appendix discusses how 

NMDP achieves the compliance by network organizations with standards 

and procedures for obtaining the informed consent of donors and 

patients, donor selection criteria, confidentiality of records, 

collection and transportation of marrow, laboratory standards, and 

maintenance of donor files in the Registry.



Informed Consent of Donors and Patients:



At each stage of the search process, NMDP requires donors to sign 

informed consent statements for procedures performed at the donor and 

transplant centers.[Footnote 33] A volunteer must sign an informed 

consent form before being listed as a donor on the Registry, and also 

before the collection of blood for initial and follow-up testing, 

infectious disease testing, and participation in research. In addition, 

consent must be obtained before notifying the transplant center that a 

donor is willing to proceed to marrow donation and before the 

administration of anesthesia. Consent must also be obtained before 

collecting blood specimens for research and before any proposed 

procedure for which the donor has not previously given consent.



According to NMDP officials, during each donor center site visit, NMDP 

staff members review about 35 randomly selected donor files. NMDP staff 

members check that each donor has signed all appropriate consent forms 

for the stages of the recruitment and search process the donor has 

completed. According to an NMDP official, since NMDP began performing 

site visits in 1998, missing or unsigned donor consent forms occurred 

in only a few cases, indicating that a high level of compliance has 

been achieved. The number of missing consent forms is not readily 

available because cumulative data are not permanently stored. 

Transplant centers are responsible for obtaining informed consent from 

each transplant patient, for collecting research blood samples that are 

sent to the NMDP repository, and for submitting baseline and follow-up 

data to the Registry. Some of the centers have separate consent forms 

specifically for the research samples and clinical data, whereas others 

incorporate consent for the research samples and clinical data into the 

informed consent document the patient signs for the transplant.



NMDP is currently collecting information on how transplant centers are 

handling the informed consent process for the research samples and 

clinical data submitted to NMDP. This information will be analyzed, and 

NMDP will evaluate whether changes in policies or procedures should be 

made to the consent process for obtaining NMDP data and research blood 

samples.



Criteria for Donor Selection:



In order to be considered for stem cell donation, donors must be from 

age 18 through 60 and in good health. Individuals with serious illness 

or those who are significantly overweight are disqualified. The donor 

must provide a medical history and acknowledge in writing that the 

history is accurate. Pertinent donor medical information is evaluated 

for acceptance or deferral according to NMDP medical eligibility 

standards and criteria set by the medical director at the local donor 

center.



NMDP monitors whether registered donors have filled out the appropriate 

medical history questionnaires, but NMDP does not store cumulative data 

on the number of missing medical history questionnaires. During each 

donor center site visit, NMDP staff members check a random number of 

health history questionnaires. However, NMDP is limited in how it 

monitors the donor selection process. Although NMDP tracks the number 

of donors who are unavailable for medical reasons, it cannot determine 

whether an unavailable donor’s medical condition was preexisting, and 

therefore should have been caught in the health screening at the time 

the donor volunteered, or whether the donor’s health changed during the 

period between registration and a request for testing prior to 

donation.



Methods to Protect Confidentiality:



NMDP requires that each participating donor center have a system for 

safeguarding donor confidentiality. The Registry identifies donors by 

code number only. Donor centers maintain donor identity and location 

and limit access to this information by using locked file cabinets and 

locked rooms.



NMDP also requires that each participating transplant center have a 

system of confidentiality in place to protect the privacy of patients. 

It provides that transplant patient identification should not appear on 

papers or publications, and the patient’s name and location should not 

be disclosed to the donor(s).



Marrow Collection and Transport:



Organizations responsible for marrow collection and transport must meet 

certain participation criteria in order to be affiliated with NMDP. 

Among other things, participating cord blood banks must be accredited 

and licensed or registered by the Food and Drug Administration for 

collection of autologous blood. Marrow collection centers must provide 

emergency and intensive care services and must be accredited by the 

Joint Commission on Accreditation of Healthcare Organizations. In 

addition, each collection center must have a licensed medical director, 

an experienced marrow collection team that regularly collects bone 

marrow, and a designated site for management of collection activities.



NMDP has established standards to ensure the proper collection and 

transportation of marrow. These require that bone marrow collection 

centers have experienced personnel to collect marrow and adequate 

resources to support collection and management activities. In addition, 

NMDP requires that collection centers maintain written standard 

operating procedures and policies for collecting, testing, labeling, 

and transporting marrow.



Laboratory Standards:



Laboratories responsible for HLA tissue typing must meet certain 

criteria in order to be affiliated with NMDP. Participating HLA typing 

laboratories must be accredited by the American Society for 

Histocompatibility and Immunogenetics (ASHI)[Footnote 34] or the 

European Foundation for Immunogenetics for techniques required by NMDP. 

Laboratories must also comply with all state and federal regulations, 

including the Clinical Laboratory Improvements Amendments of 1988 (or 

their non-U.S. equivalent) for infectious disease testing, blood 

typing, red cell antibody screening, and other tests required by NMDP.



As part of NMDP’s quality control program, participating laboratories 

must type blind samples provided by NMDP. The laboratories must 

maintain monthly error rates less than or equal to 1.5 percent. If a 

laboratory fails to meet quality control and quality assurance 

standards established by ASHI or NMDP, NMDP may require that laboratory 

to submit a corrective action plan. After the period allowed for 

corrective action, the laboratory’s contract with NMDP may be 

terminated if it still does not meet the standards.



From February 2000 through April 2002, NMDP suspended five laboratories 

responsible for HLA tissue typing. The length of suspension ranged from 

1 to 9 weeks, and reasons for suspension were related to electronic 

communication problems, overdue samples, and poor turnaround time.



Donor File Maintenance and Updates:



NMDP’s central database is updated when new donors are recruited and 

when information on existing donors changes or donors are deleted from 

the Registry. Information about newly recruited donors includes donor 

identification numbers, demographic data, and the donors’ HLA types. 

According to NMDP procedures, domestic donor centers submit data on 

donors daily through NMDP’s central database.



[End of section]



Appendix III Comments from the Health Resources and Services 

Administration:







SEP 12 2002:



TO: Janet Heinrich:



Director, Health Care - Public Health Issues:



FROM: Administrator:



SUBJECT: General Accounting Office Draft Report “Bone Marrow 

Transplants: Despite Recruitment Success, National Program May Be 

Underutilized” (GAO-02-994):



Thank you for the opportunity to provide comments on the subject draft 

report. Attached please find HRSA’s comments.



Questions may be referred to John Gallicchio on (301) 443-3099.



Betty James Duke



Signed by Betty James Duke



Attachment:



HRSA Comments on the Draft GAO Report: “Bone Marrow Transplants: 

Despite Recruitment Successes, National Program May Be Underutilized” 

(GAO-02-994):



General Comments:



The Health Resources and Services Administration (HRSA) appreciates the 

opportunity to review the draft of the report: “Bone Marrow 

Transplants: Despite Recruitment Successes, National Program May Be 

Underutilized” (GAO-02-994). The report provides an accurate and 

helpful overview of the status of the National Bone Marrow Donor 

Registry, with respect to the study mandated in the National Bone 

Marrow Registry Reauthorization Act of 1998. The report notes the 

substantial progress that has been made in achieving the statutory 

goals for the Registry, and recognizes that the challenges facing the 

Registry today are not amenable to simple solutions. We are enclosing 

HRSA’s substantive comments on the draft report and a number of 

technical comments for your consideration as you develop the final 

report. We shared the draft report with HRSA’s National Marrow Donor 

Program (NMDP) and have incorporated their suggestions in our comments.



We would like to comment on four aspects of the draft report. The first 

is progress in improving minority access to transplants through the 

Registry. The report notes that recruitment efforts focused on minority 

populations have increased the representation on the Registry of the 

major minority population groups to levels approximately equal to their 

shares of the U.S. population, and that for all racial and ethnic 

groups the likelihood of finding a match through the Registry has 

increased as the Registry has grown. Still, the likelihood of finding a 

match differs by race, with African Americans having the lowest 

probability of finding a match, in large part because of their greater 

variety in HLA types. The report concludes that some minority groups, 

especially African Americans, may never achieve the same probability of 

finding a match as Caucasians, and that attempting to close the gap 

through recruitment of donors with rare HLA types is expensive and may 

divert resources from another statutory goal for the program, 

increasing the overall number of patients who find a match and receive 

a transplant through the Registry.



We agree that recruitment of donors cannot be the sole strategy for 

improving access to unrelated donor transplants for minority patients, 

or for other patients with unusual HLA types. Also important are 

leaming which less-than-perfect HLA matches may still lead to 

successful transplants, and how to more effectively manage 

complications that arise in unrelated donor transplants; improving the 

retention of donors who have joined the Registry; encouraging patients 

who may need an unrelated donor transplant (and their physicians) to 

begin a search of the registry soon after their diagnosis; providing 

expert assistance in difficult searches; and increasing the 

effectiveness of umbilical cord blood as a source of blood stem cells 

for patients who cannot find a matched adult donor. The Registry is 

actively involved in all these areas. We think these efforts, along 

with continued recruitment of donors to replace those who are lost to 

attrition and to add:



unique HLA types to the Registry, can result in further improvements in 

access for all populations. The appropriate level of recruitment in the 

future will depend, among other things, on whether the cost of tissue 

typing continues to decline.



With respect to current minority representation on the Registry, we 

would note that the Registry donor file is comprised of two distinct 

components defined by the amount of HLA typing data available. The 

larger portion (3,081,642 as of June 30, 2002) has donors fully typed 

for HLA-A, -B and -DR. The remainder (35%) is typed only for HLA-A and 

-B. The vast majority of actual donors (>98%) are selected from the 

fully typed portion. In this most active portion of the donor file, 

each racial and ethnic group, with the exception of Caucasians, 

comprises a larger proportion of the file than their representation in 

the U.S. population.



The report also concludes that the Registry is underutilized. We agree 

that many patients who could benefit from an unrelated donor transplant 

never consult the Registry or do so too late in the course of their 

illness. Many of the ongoing efforts listed above aim to increase 

utilization of the Registry as well as increase the probability that a 

patient will find a matching donor on the Registry. We question, 

however, one specific GAO finding, that the percentage of patients in 

need of an unrelated donor transplant who search the Registry is much 

greater for African American, Hispanic and American Indian patients 

than for Caucasians. The method used to estimate the number of patients 

in need, as reported in Table 2, may involve an incorrect assumption. 

The calculation used data from the International Bone Marrow Transplant 

Registry reporting the race of related donor transplant recipients. GAO 

combined these data with fertility data to compute an estimated number 

of transplant candidates without matching sibling donors. This approach 

assumes that all appropriate candidates for sibling transplant are in 

fact transplanted. That is, there are no disparities in access to 

related donor transplant between racial and ethnic groups. Since many 

studies have found that minorities do not have the same access to 

health care as Caucasians, this assumption may be incorrect.



Finally, we wish to comment on the time required to complete a search 

of the Registry. The report notes that the median search time has been 

decreasing, but that searches still frequently take many months and 

sometimes over a year. The median search time for all patients is a 

convenient way to present data, but many factors affect search duration 

including the optimal timeframe for transplantation for each patient. 

For example, a transplant center may initiate a search for a patient at 

the same time they enroll the patient in a clinical trial of a new 

pharmaceutical agent. If the patient responds, he or she may not be a 

transplant candidate for several years but the transplant center may 

want to identify a potential donor, in case the patient’s clinical 

condition changes suddenly. In situations like this, a search may be 

ongoing for a long period of time without disadvantaging the patient. 

Alternatively, a patient with acute leukemia may need a transplant as 

soon as a suitable donor can be identified and prepared for donation. 

Decreasing search times for those patients who need to proceed to 

transplant rapidly is a major priority of the program. The NMDP has 

shown in a pilot project that it is possible to complete medically 

urgent searches in 14-21 days. Drawing on the lessons of the pilot 

project, the NMDP has made numerous procedural changes and beginning in 

September,



2002 will offer transplant centers the option of requesting that an 

urgent search be completed in 21 days or 45 days. The percentage of 

these urgent searches completed in the requested timeframe will be a 

more useful measure of performance than an overall median search time.



[End of section] 



Appendix IV: GAO Contact and Staff Acknowledgments:



GAO Contact:



Marcia Crosse, (202) 512-3407:



Acknowledgments:



The following staff members made important contributions to this work: 

Donna Bulvin, Charles Davenport, Donald Keller, Kelly Klemstine, Behn 

Miller, and Roseanne Price.



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FOOTNOTES



[1] The first source of stem cells for transplant was bone marrow, but 

now stem cells from the bloodstream or from umbilical cord blood can 

also be used. We use the term stem cell transplant to include both bone 

marrow transplants and transplants involving one of these newer sources 

of stem cells. 



[2] We use the term donors throughout this report to refer to potential 

donors on the Registry, most of whom have not donated stem cells, only 

expressed their willingness to do so.



[3] The Navy was instrumental in the founding of the Registry and has 

maintained its interest in stem cell donation over the years. HRSA and 

the Navy each contributed a little less than 20 percent of the 

Registry’s fiscal year 2002 funding (about $21 million and $20.5 

million, respectively), with program revenue and private sources 

providing the rest of the total of about $108 million.



[4] U.S. General Accounting Office, Bone Marrow Transplants: National 

Program Has Greatly Increased Pool of Potential Donors, GAO/HRD-93-11 

(Washington, D.C.: Nov. 4, 1992).



[5] HHS OIG, National Marrow Donor Program: Financing Donor Centers, 

OEI-01-95-00123 (Washington, D.C.: December 1996). 



[6] Pub. L. No. 105-196, 112 Stat. 631 (1998).



[7] IBMTR is not a donor registry; it records data about transplants 

performed.



[8] Almost 90 percent of the transplants coordinated by NMDP are for 

types of cancer, including, in descending order of frequency, chronic 

myelogenous leukemia, acute myelogenous leukemia, acute lymphocytic 

leukemia, myelodysplastic disorders, and non-Hodgkin’s lymphoma. The 

nonmalignant diseases most commonly treated by stem cells obtained 

through NMDP are aplastic anemia and several varieties of inherited 

disorders of the metabolic, immune, and blood systems.



[9] For example, the age-adjusted incidence rate per 100,000 patients 

with acute myelogeneous leukemia over the period from 1995 through 1999 

is higher for Caucasians (3.7) than for African Americans (2.9). In 

contrast, for patients with myeloma, the rate is higher for African 

Americans (11.5) than for Caucasians (5.2).



[10] An antigen is a protein found on the outside of most cells in the 

body that induces the formation of antibodies. There are a number of 

antigens in the human body, and HLA are a set of these.



[11] Recruitment groups actively seek donors, sometimes ones of a 

particular ethnic or racial heritage.



[12] Apheresis is a technique for separating blood into its components, 

using a machine that draws blood from a vein in a donor’s arm; filters 

out the desired product, such as PBSC; and returns the remaining blood 

to the donor.



[13] There are seven such donor centers. Three of these are in Germany, 

and the others are located in the Netherlands, Israel, Sweden, and 

Norway.



[14] HRSA consults with the Department of State on proposed membership 

of foreign organizations.



[15] These countries are Australia, Austria, Canada, the Czech 

Republic, England, France, Ireland, Italy, Japan, Singapore, Spain, 

Switzerland, and Taiwan.



[16] For example, the American Bone Marrow Donor Registry of 

Mandeville, Louisiana, is composed of a Patient Advocacy Office that 

coordinates and processes search requests and a Donor Services Division 

that educates, recruits, and maintains the records of donors. Moreover, 

it has regional components, also called registries. Other U.S. 

registries include the Caitlin Raymond International Registry of 

Worcester, Massachusetts, and the Gift of Life Foundation of Boynton 

Beach, Florida. In addition, there are a number of U.S. cord blood 

banks including ones in New York, New Jersey, Missouri, and 

Massachusetts (part of the Caitlin Raymond International Registry).



[17] Donors are considered too old to donate at age 61.



[18] These include confirmation of donor availability and willingness, 

satisfactory results of laboratory tests done on the donor, and the 

patient’s desire to continue the search. 



[19] For example, the African American difference of 2 percentage 

points is 17 percent of that group’s 12 percent share of the 

population.



[20] This probability was computed in 2001 by considering all patients 

who had searched the Registry by that time and, using NMDP’s matching 

criteria, asking what proportion of these would have found a match 

during each year of the Registry’s existence, given the donors on the 

Registry during that year. This theoretical probability has advantages 

over the observed proportion of matches as a measure of access by 

patients. One is that a large and representative number of searching 

patients are repeatedly applied to the Registry over its history so 

that any fluctuations cannot be a result of fluctuations in the numbers 

or kinds of patients searching from year to year. Another advantage is 

that today’s definition of a match has been applied throughout the 

years covered so that any fluctuations cannot be a result of changes in 

that definition over the years.



[21] A fully typed donor is one for whom all crucial antigens are 

determined at the time the donor volunteers.



[22] See app. I for an explanation of how we estimated the number of 

patients in need.



[23] NMDP has used a similar method of estimation and draws a similar 

conclusion about possible underutilization.



[24] Cancellation of a preliminary search means that 45 days have 

occurred since the search without a formal search having been 

initiated. Cancellation of a formal search means that the transplant 

center has submitted a particular form indicating a desire to terminate 

the search and included a reason for doing so. 



[25] Although several blood banks list their cord blood units with 

NMDP, others, including the largest, the New York Blood Center, do not, 

and thus NMDP cannot facilitate transplants from those banks.



[26] Under CPI, NMDP allows up to three notices of noncompliance with a 

particular standard and sets interim goals to be met within a specified 

review period after each notice. After a third notice, centers are 

placed on probation. Failure to meet the requirements of the 

probationary period may result in termination.



[27] The HHS OIG recommended that HRSA standardize contracts between 

NMDP and donor centers for donor services to improve the cost 

efficiency of the centers and to link payment to performance. HRSA 

included this requirement in its 1997 contract with NMDP to operate the 

Registry.



[28] This registry, located in Milwaukee, registers bone marrow 

transplants, not donors like the other registries discussed in this 

report. The data used in our estimations were obtained from the 

Statistical Center of IBMTR and Autologous Blood and Marrow Transplant 

Registry (ABMTR). The analysis has not been reviewed or approved by the 

Advisory Committees of the IBMTR and ABMTR.



[29] We determined this average by taking the median Caucasian 

fertility rate for the years from 1989 through 1995. Fertility rates 

for non-Hispanic Caucasians were not available for earlier years. We 

did not include rates for years after 1995 because we do not think many 

of the transplants occurring during the years 1997 through 2000 were 

done for patients born after 1995. Because fertility rates tended to be 

higher before about 1973, when some of the patients seeking transplants 

during the period of our analysis, 1997 through 2000, were born, the 

use of the 1989 through 1995 rates results in an underestimation of the 

average number of siblings and a consequent overestimation of the 

number of patients in need of unrelated donor transplants. The effect 

of this consideration of the 1989 through 1995 rates is counterbalanced 

to an unknown extent because (1) the fertility rates count half 

siblings and dead siblings as well as living full siblings and (2) the 

fertility rates count all of a woman’s live births, including those 

that occur after the patient needs a transplant. The effect of these 

two counterbalancing considerations is to overestimate of the number of 

siblings available to donate and underestimate the number of patients 

in need. The net effect of the choice of 1989 through 1995 rates and 

the considerations concerning the fertility rates on the estimation of 

the number of patients in need is not known. 



[30] See, for example, R.M. Mayberry, F. Mili, and E. Ofili, “Racial 

and Ethnic Differences in Access to Medical Care,” Medical Care 

Research and Review, vol. 57, Supplement 1 (2000), pp. 108-145.



[31] R.P. Gale, “Potential Utilization of a National HLA-Typed Donor 

Pool for Bone Marrow Transplantation,” Transplantation, vol. 42, no. 1 

(1986), pp. 54-58.



[32] We have not related the number of potential recipients estimated 

in this third way with the numbers of preliminary searches for patients 

with the selected diseases, only with the numbers of transplants.



[33] Informed consent refers to the process of helping an individual 

weigh the risks against the benefits of a procedure or treatment. By 

signing a form, an individual consents to undergo a procedure after 

being fully informed of the risks and benefits. 



[34] ASHI is an accrediting body that has established standards that 

all histocompatibility laboratories must meet if their services are to 

be considered acceptable. 



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