|
|
| |||||||||||||||||||||||||||||||||||||||
Background and Methods Allogeneic bone marrow transplantation is curative in a substantial number of patients with hematologic cancers, marrow-failure disorders, immunodeficiency syndromes, and certain metabolic diseases. Unfortunately, only 25 to 30 percent of potential recipients have HLA-identical siblings who can act as donors. In 1986 the National Marrow Donor Program was created in the United States to facilitate the finding and procurement of suitable marrow from unrelated donors for patients lacking related donors.
Results During the first four years of the program, 462 patients with acquired and congenital lymphohematopoietic disorders or metabolic diseases received marrow transplants from unrelated donors. The probability of engraftment by 100 days after transplantation was 94 percent, although 8 percent of patients later had secondary graft failure. The probability of grade II, III, or IV acute graft-versus-host disease was 64 percent, and the probability of chronic graft-versus-host disease at one year was 55 percent. The rate of disease-free survival at two years among patients with leukemia and good prognostic factors was 40 percent and among patients at higher risk, 19 percent. Twenty-nine percent of the patients with aplastic anemia were alive at two years, and the rate of two-year disease-free survival among patients with myelodysplasia was 18 percent. For patients with congenital immunologic or nonimmunologic disorders, the probability of survival was 52 percent.
Conclusions The National Marrow Donor Program has benefited a substantial number of patients in need of marrow transplants from closely HLA-matched unrelated donors and has facilitated the recruitment of unrelated donors into the donor pool and the access to suitable marrow.
Methods
The NMDP
The NMDP was established in 1986 through a contract from the U.S. Navy to the American Red Cross. Responsibility for the contract was transferred to the National Heart, Lung, and Blood Institute in February 1989. The procedure and policies of the NMDP have been described previously29.
Patients
The study population consisted of 462 patients with malignant or nonmalignant diseases who received marrow transplants at centers in the United States between December 16, 1987, and November 3, 1990 (Table 1 and Table 2). Among the patients with leukemia, those projected to have a good outcome after transplantation included patients with acute leukemia in first or second complete remission and those with chronic myelogenous leukemia in the primary chronic phase. Patients with acute leukemia in more than second remission or in relapse and patients with chronic myelogenous leukemia in secondary or a more advanced chronic phase or in accelerated or blastic phase were considered to be at high risk. The infusion of marrow from an unrelated donor was the second transplantation procedure for six patients, and seven patients received two marrow transplants from unrelated NMDP donors.
|
|
Methods for the prophylactic treatment of graft-versus-host disease (GVHD) varied according to the transplantation center. Ninety-five patients (21 percent) received marrow depleted of donor T cells: 70 of the 352 patients with leukemia (20 percent), 15 of the 63 patients with marrow-failure syndromes (24 percent), 9 of the 41 patients with a congenital disorder (22 percent), and 1 of the 6 patients with other malignant diseases (17 percent).
Donor Selection and Collection and Processing of Bone Marrow
The characteristics of the donors are shown in Table 2. The matching of donors and recipients was based on HLA serotyping performed according to standard techniques30. A mismatch of one antigen was categorized as minor if the mismatched antigen was cross-reactive and as major if the antigen was not cross-reactive. Fifty-three donor centers provided at least 1 marrow donor, and three of these centers provided 50 or more donors. Forty-two collection facilities performed the marrow harvests; five centers harvested marrow from more than 25 donors each. The transported marrow was infused without manipulation in 215 patients (47 percent), whereas in 247 (53 percent) it was manipulated for the following reasons: volume reduction (13 patients, 3 percent), red-cell depletion for ABO incompatibility (139 patients, 30 percent), T-cell depletion for the prevention of GVHD (67 patients, 15 percent), or both ABO incompatibility and the prevention of GVHD (28 patients, 6 percent).
Data Collection
The transplantations were performed at 28 centers in the United States: 21 (75 percent) of the centers performed 1 to 9 transplantations, 1 center performed 12 procedures, 1 center 19 procedures, and 5 centers more than 25 primary transplantations (27, 36, 56, 83, and 129 procedures). The median length of follow-up was 1.5 years (range, 0.3 to 3.7). Data on survival were gathered until September 1, 1991, in all but two transplantation centers, in which the cutoff date was March 1, 1991. We considered that all patients were suitable for evaluation for engraftment, acute GVHD, and chronic GVHD. The day of engraftment was defined as the first of three consecutive days on which the neutrophil count exceeded 500 per cubic millimeter. Thus, patients in whom engraftment did not occur did not have a neutrophil count of more than 500 per cubic millimeter for three consecutive days at any time after transplantation. Patients with initial engraftment in whom severely hypocellular marrow or an absolute neutrophil count of less than 500 per cubic millimeter recurred were considered to have secondary graft failure. The stage of involvement of the skin, liver, and intestine with acute GVHD was measured individually according to standard criteria,31 and a grade was assigned on the basis of the sum of the individual stages: a grade of 0 was assigned for a score of 0; a grade of I for a score of 1 to 2; a grade of II for a score of 3 to 4, except in cases in which the skin, liver, or intestine alone was considered to be in stage 4, in which case a grade of III was assigned; and a grade of III to IV for a score of 5 or more. Chronic GVHD was assessed as limited (mild skin involvement only) or extensive (skin, liver, and intestinal involvement).
Statistical Analysis
Disease-free survival curves were calculated by Kaplan-Meier analysis32. The length of time from the first transplantation to an event was defined in three ways: as the interval between transplantation and relapse among patients who were reported to be free of their disease after transplantation, as the interval from transplantation to day 28 among patients who survived at least 28 days but were never free of their disease after transplantation, or as the interval between transplantation and death among patients who did not fit into the first two categories. In univariate analyses, the log-rank statistic33 was determined, and its level of significance is given. All values reflect two-sided P values. The two-year disease-free survival rates and their 95 percent confidence intervals are given. In multivariate analyses involving the occurrence of disease-free survival and relapse among patients with leukemia, the proportional-hazards model34 was used with the following covariates: recipient's age, recipient's cytomegalovirus status, the level of HLA matching (a disparity of 0 or 1 antigen), donor's age, donor's sex, the need to manipulate marrow to prevent GVHD, the interval between diagnosis and transplantation, the type of leukemia (chronic vs. acute), and leukemia status (good vs. poor prognostic factors). Only variables whose coefficients had P values of 
0.10 are reported.
For nonfatal events, such as engraftment, the occurrence of grade II to IV or grade III to IV acute GVHD, or the occurrence of extensive chronic GVHD, death was defined as a censored variable in the life-table analyses. The censoring date for the analysis involving nonfatal events was the date of the last regular follow-up visit or the date of death. Both Kaplan-Meier and proportional-hazards models were employed. The following independent variables were considered for these dependent variables: recipient's age, recipient's cytomegalovirus status, the level of HLA matching, the use of T-cell-depleted marrow to prevent GVHD, and a diagnosis of chronic rather than acute myelogenous leukemia. An independent variable appearing in several proportional-hazards models was always coded in the same way, and only the variables whose coefficients had P values of 0.10 are reported. Results are given as the probability estimate ±1.96 times the standard error (i.e., the 95 percent confidence interval).
Results
Identification of Unrelated Donors
Among the 462 patients, 306 (66 percent) received marrow from a donor serologically matched for HLA-A, B, and DR antigens, whereas 61 (13 percent) received marrow with a minor mismatch of one HLA antigen and 92 (20 percent) received marrow with a major mismatch of one class I or class II HLA antigen. In three cases (1 percent) there was a mismatch of more than one HLA antigen. The median interval between the initiation of a preliminary search for a donor and marrow transplantation was 196 days (range, 17 to 1037). For patients with chronic myelogenous leukemia, the median interval was 252 days (range, 50 to 1037). For patients with other diagnoses, the median interval was 164 days (range, 17 to 709).
Engraftment
The probability of engraftment by 100 days after transplantation was 0.94 ±0.03 (95 percent confidence interval, 0.91 to 0.97); engraftment occurred a median of 22 days after transplantation (range, 6 to 84). On multivariate analysis, an accelerated rate of engraftment was independently associated with the receipt of marrow depleted of T cells (P<0.001), the receipt of HLA-matched marrow (P<0.001), and increasing patient age (P = 0.05).
Eight percent of the patients had graft failure between 25 and 263 days after transplantation. Among the variables examined, only the use of marrow depleted of T cells was significantly associated with secondary graft failure after initial engraftment (0.14 ±0.08 vs. 0.07 ±0.04, P = 0.04). One year after transplantation, 11 of 143 patients whose transfusion history could be evaluated continued to require transfusions of platelets (2 patients), red cells (2), or both (7).
GVHD
The probability of having grade II, III, or IV acute GVHD by 100 days after transplantation was 0.64 ±0.05 (95 percent confidence interval, 0.59 to 0.69), and a substantial number of the patients with GVHD had severe (grade III to IV) acute GVHD (0.47 ±0.06) (Figure 1A). Multivariate analysis showed that the development of grade III to IV acute GVHD was independently associated with the use of marrow that had not been depleted of T cells (P<0.001) (Figure 1B) and increasing patient age (P = 0.001) (Figure 1C). The development of acute GVHD was not associated with the level of HLA disparity, as defined by serologic analysis (Figure 1D).
|
|
Patients with Leukemia
The patients with leukemia were followed for a median of 1.5 years (range, 0.72 to 3.7). The probability of disease-free survival at two years among patients with leukemia and good prognostic factors was 0.40 ±0.08, whereas it was 0.19 ±0.06 (P<0.001) among patients with leukemia and poor prognostic factors. Among patients with acute leukemia in first or second remission, the probability of disease-free survival was 0.45 ±0.13, which was superior to that among patients with more advanced disease (0.19 ±0.08, P<0.001). Similarly, among patients with chronic myelogenous leukemia in the primary chronic phase, the disease-free survival at two years was 0.37 ±0.10, which was higher than that among patients with more advanced disease (0.21 ±0.09, P = 0.02). Although these results suggest that patients with acute leukemia had a more favorable probability of disease-free survival than patients with chronic leukemia, multivariate analysis in which recipient's age was included as a variable indicated the reverse (P = 0.02). Several variables were examined by multivariate analysis for their effect on the survival of patients with leukemia. Those found to be significant are presented in Table 3. Seventy of the 352 patients with leukemia received marrow depleted of T cells. There was a trend (P = 0.10) toward improved disease-free survival among these patients. Considering the results of multivariate analysis, it is not surprising that patients under the age of 18 years who had good prognostic factors for leukemia did well after transplantation. Among 41 such patients, the probability of disease-free survival at two years was 0.53 ±0.15. In contrast, the probability of disease-free survival among patients over the age of 18 who had poor prognostic factors for leukemia was 0.11 ±0.06 (Figure 3).
|
|
|
The median interval from diagnosis to transplantation was 0.9 year (range, 0.2 to 8.2) among patients with aplastic anemia and 0.9 year (range, 0.3 to 10.3) among patients with myelodysplasia. The probability of survival at two years was 0.29 ±0.17 among patients with aplastic anemia or paroxysmal nocturnal hemoglobinuria (Figure 5). However, 4 of the 10 patients with aplasia who were alive one year after transplantation continued to require transfusions of platelets (2 patients), red cells (1), or both (1). Although the probability of survival among patients with myelodysplasia was 0.24 ±0.15, not all patients were disease-free. The probability of disease-free survival at two years was 0.18 ±0.14 (Figure 5).
|
Forty-one patients received a transplant for the treatment of a congenital disorder reported to be amenable to therapy with marrow from an HLA-identical sibling35. The immunodeficiency disorders included combined immunodeficiency syndromes (9 patients), Wiskott-Aldrich syndrome (5), T-cell deficiency (2), common variable immunodeficiency (2), ataxia-telangiectasia (2), and leukocyte-adhesion deficiency (1). Among the patients treated for non-immunodeficiency congenital disorders, the majority had Hurler's syndrome (10). Other diagnoses included Sanfilippo's syndrome (2 patients), globoid leukodystrophy (2), Fanconi's anemia (1), osteopetrosis (1), Hunter's syndrome (1), Gaucher's disease (1), and familial erythrophagocytic lymphohistiocytosis (2). In this group of patients, the probability of engraftment within 100 days after transplantation was 0.96 ±0.07, whereas the probability of having grade II, III, or IV acute GVHD within 100 days was 0.37 ±0.17. The probability of having extensive chronic GVHD at one year was 0.08 ±0.11. Because of the nature of these diseases, it is not currently possible to address whether these patients were disease-free after transplantation. However, the probability of survival among patients with congenital immunodeficiency, hematologic, or metabolic disorders two years after transplantation was 0.52 ±0.17
Patients with Other Malignant Conditions
One of the four patients with non-Hodgkin's lymphoma survived (>604 days at the time survival data were censored). This patient was only 2.6 years of age at the time of transplantation and did not have severe acute or chronic GVHD, whereas the other patients were all over the age of 35 years and either died soon after transplantation (day 3) or had severe (grade III) acute GVHD and died within 120 days after transplantation. The patient with multiple myeloma, who was 37.5 years of age at transplantation, survived (>589 days at the time survival data were censored), and the patient with Hodgkin's disease, who was 28.8 years old at transplantation, died of grade III acute GVHD 114 days after transplantation.
Patients Who Received Second Transplants
Five of the six patients whose NMDP-facilitated transplant was their second transplant had received an autologous transplant for the treatment of acute leukemia or lymphoma (acute lymphoblastic leukemia in one, non-Hodgkin's lymphoma in one, and acute nonlymphocytic leukemia in three). One of these five patients was alive more than 400 days after transplantation, and another 1150 days after transplantation. The sixth patient had received a transplant for the treatment of aplastic anemia 1 month earlier from an unrelated donor identified through the Anthony Nolan Registry in England, and he died 70 days after receiving his second transplant.
Seven patients received a second marrow graft from an unrelated donor identified through the NMDP because of primary failure of the marrow to engraft or secondary graft failure after their first transplantation. The same donor was used for only one of these patients. Three had received marrow that had not been depleted of T cells, and four received marrow that had been depleted of T cells. The median interval between the first and second transplantations was 64 days (range, 55 to 464). One of the seven patients survived. This patient (who had chronic myelogenous leukemia in chronic phase) received an infusion of cryopreserved autologous marrow when his second marrow infusion from an unrelated donor failed to engraft.
Complications and Causes of Death
One hundred thirty-eight patients (30 percent) had interstitial pneumonia, 109 (24 percent) were reported to have had hepatic dysfunction consistent with venoocclusive disease, 35 (8 percent) to have had cardiac failure, and 8 (2 percent) to have had a B-cell lymphoproliferative disorder. Lymphoproliferative disorders were observed among patients who received marrow depleted of T cells (5 patients [5 percent]) as well as those who did not (3 patients [1 percent]). Furthermore, lymphoproliferative disorders were observed among patients who did not have acute GVHD (3 of 213 patients) as well as among those who did (5 of 249 patients).
Of the 462 patients, 307 (66 percent) have died. The primary and secondary causes of death are listed in Table 4.
|
Discussion
Transplantation of bone marrow from an HLA-identical sibling results in prolonged leukemia-free survival in approximately 50 percent of patients with good prognostic factors and in up to 20 percent of patients with advanced leukemia1,2,36,37. The survival rate among patients with aplastic anemia is 50 to 80 percent for patients receiving HLA-identical grafts,38 and disease-free survival among patients with myelodysplasia ranges from 30 to 50 percent39. Several studies of marrow transplantation with related donors other than genotypically HLA-identical siblings indicate that the probability of having serious complications after transplantation, including graft failure, acute and chronic GVHD, fatal infections, and lymphoproliferative disorders, is increased as compared with that observed after the transplantation of marrow from an HLA-identical sibling and is higher among recipients of grafts that are not matched for two or three HLA loci than among recipients of marrow with a single HLA disparity17,40,41,42,43,44,45,46,47,48,49. Similarly, reports from individual centers that involve 8 to 55 recipients who received marrow from closely HLA-matched unrelated donors indicate that both the incidence and the severity of complications may be increased in these patients12,13,15,17,18,19,20,21,22.
The probability of graft failure after an infusion of marrow from a family member correlates with the degree of HLA incompatibility41,45,50 and the use of T-cell depletion to prevent acute and chronic GVHD21,50,51,52. In the present NMDP study of 462 patients, graft failure was evaluated by calculating the probability of both initial myeloid engraftment and secondary marrow failure. The probability of engraftment for the entire study population was lower than that reported by Beatty et al.22 but similar to that reported by Ash et al.,21 who used in vitro T-cell depletion to prevent GVHD. In our study the probability of engraftment within 100 days after transplantation was 0.94 ±0.03, with an accelerated rate of engraftment independently associated with the receipt of marrow depleted of T cells and with the receipt of HLA-matched marrow. The difference in the length of time to engraftment between marrow depleted of T cells and unmanipulated marrow may be due to factors other than the use of T-cell-depleted marrow, such as the use of post-transplantation chemoprophylaxis regimens that include intravenous methotrexate, which would be expected to delay engraftment. Transplantation centers that used in vitro T-cell depletion to prevent GVHD did not use methotrexate, but rather used corticosteroids, cyclosporine, and antithymocyte globulin. In contrast, most centers that infused unmodified marrow used methotrexate to prevent GVHD after transplantation.
The probability of severe acute GVHD was higher in our patients than in recipients of marrow from HLA-matched siblings; the probability of having grade II, III, or IV acute GVHD was 0.64 ±0.05. This high probability is comparable to that observed among recipients of unmanipulated marrow mismatched for one or two HLA antigens from a family member22,41. Yet in our series the level of donor-recipient HLA disparity, as evaluated by serotyping, did not affect the probability of the development of acute GVHD. This probably reflects the fact that phenotypically HLA-identical unrelated pairs of donors and recipients have important differences in structural polymorphisms that are not detectable by conventional serotyping for HLA-A, B, and DR alloantigens. These differences can be detected in the HLA class I region by one-dimensional isoelectric focusing53,54,55 and in the class II region by restriction-fragment-length polymorphism56,57 and hybridization with sequence-specific oligonucleotide probes56,58,59,60. In the present study, in which 272 donor-recipient pairs had interpretable results of mixed-lymphocyte culture, there was no correlation between the level of reactivity and the incidence or severity of acute GVHD (data not shown).
Despite the increased risk of graft failure and severe acute and chronic GVHD, this study demonstrates in a large patient population that the transplantation of marrow from unrelated donors can be an effective treatment for certain hematologic cancers and non-neoplastic disorders. Among 352 patients with leukemia, the probability of disease-free survival at two years was 0.40 ±0.08 for patients with good prognostic factors and 0.19 ±0.06 for patients with poor prognostic factors. Post-transplantation relapse is a serious problem for recipients of marrow from HLA-identical siblings, with patients who undergo transplantation while in relapse at the highest risk61. In our study, the stage of disease was not associated with the risk of relapse, but it was associated with the risk of death.
Although recipients of HLA-identical marrow depleted of T cells for the treatment of advanced leukemia or chronic myelogenous leukemia are at increased risk of relapse after transplantation,62,63 recipients of T-cell-depleted marrow from unrelated donors do not appear to be at a similar increased risk for relapse. The low probability of relapse in the NMDP patient population is encouraging and suggests that transplants from unrelated donors may offer a considerable graft-versus-leukemia effect. However, the effect of other factors reported to influence the probability of post-transplantation relapse, including the pretransplantation preparative regimen, the presence of GVHD, and post-transplantation immunosuppression,61,64,65,66 has not been examined, and a longer follow-up is necessary for a definitive analysis of relapse in this patient population.
Seventy of the 352 patients with leukemia received marrow depleted of T cells for the prevention of acute and chronic GVHD. The use of T-cell-depleted marrow was associated with more rapid engraftment, a decrease in the incidence and severity of GVHD, and a reduction in the mortality rate by approximately 60 percent during the first 50 days after transplantation. Thereafter, there was no difference in survival among patients with leukemia who received T-cell-depleted marrow and those who received unmanipulated marrow. Since this initial analysis does not reveal an increase in relapse among recipients of T-cell-depleted marrow, it is unclear why the leukemia-free survival rate was only marginally improved for these patients as determined by multivariate analysis (P = 0.10). The effects of T-cell depletion in our study should be interpreted cautiously, however, since only 5 of the 28 transplantation centers used this approach to prevent GVHD, and T-cell depletion may be a marker for the effects of the complete regimen or any one of the components of the regimen used for the marrow procedure. Nevertheless, the finding is similar to that observed in a retrospective review that analyzed the effect of T-cell depletion on the outcome of marrow transplantation from related donors other than HLA-identical siblings50.
For young adults who have an HLA-matched family member, bone marrow transplantation is the preferred treatment for severe aplastic anemia38,67,68. HLA-incompatible family members or closely matched unrelated persons have donated marrow to patients lacking an HLA-identical sibling16,17,20,69. In the present study, patients with aplastic anemia generally had poor prognostic characteristics70. All patients had received multiple blood transfusions, and there was a relatively long interval between diagnosis and transplantation. However, the probability of survival after this procedure in this group of patients (0.29 ±0.17) is probably superior to that with other available therapies, since in qualifying for transplantation protocols involving unrelated donors, it is likely that these patients had not responded to immunosuppressive or cytokine therapy.
Approximately 50 to 60 percent of patients with myelodysplasia who are under the age of 30 years are disease-free three years after the transplantation of marrow from HLA-matched siblings, whereas the probability of disease-free survival is only 25 percent among patients over the age of 3039,71,72,73. When compared with the results of the transplantation of marrow from HLA-identical siblings, the results of the 32 procedures involving marrow from unrelated donors in the present study are disappointing; the probability of disease-free survival at two years was 0.18 ±0.14. The median age of these patients was 24.3 years, and the distribution of patients within the diagnostic subgroups was not skewed toward advanced disease; only 11 of the 32 patients had excess blasts. Thus, neither older age nor advanced disease accounted for the poor outcome.
Recipients of partially matched transplants from family members are at higher risk for infectious complications and lymphoproliferative disorders than are recipients of transplants from HLA-identical siblings46,48. This observation has been extended to recipients of marrow from unrelated donors15,21 and is true of the present study, in which infection, interstitial pneumonia, or both contributed to 58 percent of the deaths and in which secondary lymphoproliferative disorders developed in eight patients.
Although the optimal approaches to the selection of an unrelated donor and the prevention of graft failure and acute and chronic GVHD remain to be defined, this report demonstrates that transplantation with marrow derived from an unrelated donor can benefit many patients.
We are indebted to Ms. Patricia Coppo and her staff of donor-search coordinators at the NMDP, to Ms. Jessie Song and Ms. Qin Tian for computer-programming support, and to Ms. Carolynn Barnes for assistance with the preparation of the manuscript.
Source Information
From the Memorial Sloan-Kettering Cancer Center, New York (N.A.K.); University of Minnesota, Minneapolis (G.B., A.F., J.M., P.M., D.S.); Fred Hutchinson Cancer Center, Seattle (J.A.H., J.S., E.D.T.); Medical College of Wisconsin, Milwaukee (R.C.A.); University of Utah School of Medicine, Salt Lake City (P.G.B.); University of Texas, Houston (R.C.); University of California, Los Angeles (J.G.); University of Kentucky, Lexington (J.H.-D.); Irwin Memorial Blood Center, San Francisco (H.A.P.); Vancouver General Hospital, Vancouver, B.C., Canada (G.L.P.); and Stanford University Medical Center, Stanford, Calif. (K.G.B.). The centers participating in this study from the National Marrow Donor Program are listed in the Appendix.
Address reprint requests to Dr. Kernan at Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.
References
The following centers participated in the National Marrow Donor Program: Transplantation centers: Fred Hutchinson Cancer Research Center; University of Minnesota Hospital and Clinic; UCLA; Medical College of Wisconsin; Memorial Sloan-Kettering Cancer Center; University of Kentucky Medical Center; J. Hillis Miller Center-Gainesville; Indiana University Hospital-Indiana University Medical Center; University of Nebraska Medical Center; Seattle Veterans Affairs Medical Center; City of Hope National Medical Center; University of Iowa Hospitals and Clinics; Cleveland Clinic Foundation; Ohio State University Hospital; Hahnemann University Hospital; Georgetown University Hospital-Lombardi Cancer Research Center; Stanford University Medical Center; Montefiore University Hospital-University of Pittsburgh; Children's-Brigham and Women's Hospital Transplant Unit; Children's Hospital of Los Angeles; Wayne State University-Harper Hospitals; Vanderbilt University Medical Center; Children's Hospital Medical Center, Cincinnati; All Children's Hospital, St. Petersburg; Children's Hospital of Philadelphia; University of California, San Francisco, Pediatric Bone Marrow Transplantation Program; Johns Hopkins Oncology Center; and University of Southern Florida; Donor centers: Blood Center of Southeastern Wisconsin; American Red Cross, St. Paul Region; Puget Sound Blood Center; Sacramento Medical Foundation Blood Center; Heart of America Bone Marrow Donor Registry; National Institutes of Health Marrow Donor Center; American Red Cross Central California Region, San Jose; American Red Cross, Greater Upstate New York Region, Albany Site; Central Indiana Regional Blood Center; American Red Cross Los Angeles-Orange Counties Region; Europdonor Foundation; American Red Cross, Carolinas Region; American Red Cross, Penn-Jersey Region; American Red Cross, Pacific Northwest Region; American Red Cross, Great Lakes Region; American Red Cross, Northwest Ohio Region; San Diego Blood Bank; Blood Center at Wadley Institutes; Greater New York Blood Program; Community Blood Bank; American Red Cross, Detroit; American Red Cross, Rochester; American Red Cross, Burlington; American Red Cross, Madison; American Red Cross, Baltimore; Civitan Regional Blood Center; Florida Reference Labs; American Red Cross, Dedham; American Red Cross, Fort Wayne; American Red Cross, Columbus; Johns Hopkins Hemapheresis Center; Irwin Memorial Blood Bank; Stanford University Blood Center; Blood Bank, San Bernardino-Riverside; American Red Cross, Farmington; American Red Cross, Atlanta; American Red Cross, Wichita; American Red Cross, Syracuse; Central Blood Bank; American Red Cross, Columbia; Hoxworth Blood Center; American Red Cross, Cleveland; American Red Cross, Peoria; Dana-Farber Cancer Institute; American Red Cross, Omaha; Spokane and Inland Empire Blood Bank; South Florida Regional Blood Service; Oklahoma Blood Institute; American Red Cross, Johnstown; American Red Cross, Washington; Michigan Community Blood Center; Belle Bonfils Memorial Blood Center; and New Jersey HLA Registry Foundation; Collection centers: University of Minnesota Hospital and Clinic; Virginia Mason Clinic; Milwaukee County Medical Complex; Mercy General Hospital; Medical College of Wisconsin; Genesee Hospital; UCLA; Indiana University Medical Center; Stanford University Medical Center; Wayne State University; Johns Hopkins Oncology Center; Emory Clinic; Georgetown University Hospital; Memorial Sloan-Kettering Cancer Center; University Hospital, Leiden; Cleveland Clinic Foundation; Hahnemann University Hospital; Kaiser Health Center East; All Children's Hospital; Dartmouth-Hitchcock Medical Center; Baylor University Medical Center; Shands Hospital, University of Florida; University of California, San Diego, Medical Center; University of Wisconsin; Kansas City Internal Medicine; Ohio State University; New England Medical Center; Montefiore Hospital; University of Nebraska Medical Center; City of Hope National Medical Center; Pacific Presbyterian Hospital; University of Connecticut John Dempsey Hospital; Children's Hospital Medical Center; University of California Medical Center; University of Kentucky Medical Center; Hotel Dieu Hospital, Louisiana State University Medical Center; Oklahoma Memorial Hospital; Lawrence Memorial Hospital; George Washington University Hospital; Dana-Farber Cancer Institute; North Carolina Baptist Hospital; and University of Colorado Health Sciences Center.
| |||||||||||||||||||||||||||||||||||||||
Related Letters:
Marrow Transplants from Unrelated Donors
Scornik J. C., Kernan N. A., Hansen J. A., Blume K. G.
Extract |
Full Text
N Engl J Med 1993;
329:362-363, Jul 29, 1993.
Correspondence
This article has been cited by other articles:
