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Background Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord–blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Methods Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Results Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor — that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit — that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Conclusions Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.)

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depend on a specific early diagnosis. Since 1994, we have come a long way in understanding the role of proinflammatory cytokines at the cellular level both within the fetus and in a possible relationship to fetal brain damage. Heretofore, birth markers such as Apgar scores, electronic fetal monitoring, neuroimaging, and onset of seizures in the first 48 hours are not specific and not sensitive. In the 1994 editorial, I stated that more accurate markers of hypoxia were needed and should develop as our understanding of the biochemical mechanisms unfold. Now that the biochemical mechanisms are unfolding, and once we can get specific levels of cytokines in the blood and the cerebrospinal fluid, interventions can be tried under randomized and controlled conditions with the hope of preventing some of the devastating consequences of hypoxic-ischemic brain damage.-RCC) ABSTRACTAt present, an estimated 1 in 5 leukemic patients receives a bone marrow or stem cell transplant from an unrelated donor or an HLA-mismatched related donor. Cord blood grafts from unrelated donors have been successful, most often in children. Hematopoiesis recovers more slowly than with bone marrow grafts, contributing to relatively high rates of infection and early death. This study examined outcomes in adults with leukemia, from 16 to 60 years of age, who received transplants of hematopoietic stem cells from unrelated donors. Data were acquired from the International Bone Marrow Transplant Registry and from the National Cord Blood Program of the New York Blood Center. Cord blood was mismatched for 1 HLA antigen in 34 cases and for 2 antigens in 116 others. Bone marrow had 1 HLA mismatch in 83 cases, whereas 367 patients received HLA-matched bone marrow. The patients given cord blood were younger than those given marrow transplants and likelier to have advanced leukemia.Median follow-up intervals were 4 years for marrow recipients and 40 months for those given cord blood transplants. For patients whose neutrophils and platelets recovered, recovery times were shorter after marrow transplantation and longest (27 days) after cord blood transplantation. A similar pattern was found for platelet recovery, with a median recovery interval of 60 days after cord blood transplantation. There were no major differences in recovery of either neutrophils or platelets after 12 months. Acute graft-versus-host disease (GVHD) was less likely after transplanting mismatched cord blood than mismatched bone marrow. Among patients who lived 3 months or longer, chronic GVHD was most frequent in patients given cord blood. The fewest treatment-related deaths were in patients given HLAEthics, Medicolegal Issues, and Public Policy 295