Analysis of 462 Transplantations from Unrelated Donors Facilitated by the National Marrow Donor Program
Nancy A. Kernan, Glenn Bartsch, Robert C. Ash, Patrick G. Beatty, Richard Champlin, Alexandra Filipovich, James Gajewski, John A. Hansen, Jean Henslee-Downey, Jeffrey McCullough, Philip McGlave, Herbert A. Perkins, Gordon L. Phillips, Jean Sanders, David Stroncek, E. Donnall Thomas, and Karl G. Blume
Background and Methods Allogeneic bone marrow transplantationis curative in a substantial number of patients with hematologiccancers, marrow-failure disorders, immunodeficiency syndromes,and certain metabolic diseases. Unfortunately, only 25 to 30percent of potential recipients have HLA-identical siblingswho can act as donors. In 1986 the National Marrow Donor Programwas created in the United States to facilitate the finding andprocurement of suitable marrow from unrelated donors for patientslacking related donors.
Results During the first four years of the program, 462 patientswith acquired and congenital lymphohematopoietic disorders ormetabolic diseases received marrow transplants from unrelateddonors. The probability of engraftment by 100 days after transplantationwas 94 percent, although 8 percent of patients later had secondarygraft failure. The probability of grade II, III, or IV acutegraft-versus-host disease was 64 percent, and the probabilityof chronic graft-versus-host disease at one year was 55 percent.The rate of disease-free survival at two years among patientswith leukemia and good prognostic factors was 40 percent andamong patients at higher risk, 19 percent. Twenty-nine percentof the patients with aplastic anemia were alive at two years,and the rate of two-year disease-free survival among patientswith myelodysplasia was 18 percent. For patients with congenitalimmunologic or nonimmunologic disorders, the probability ofsurvival was 52 percent.
Conclusions The National Marrow Donor Program has benefiteda substantial number of patients in need of marrow transplantsfrom closely HLA-matched unrelated donors and has facilitatedthe recruitment of unrelated donors into the donor pool andthe access to suitable marrow.
Allogeneic marrow transplantation is an accepted form of treatmentthat can provide a cure for patients with hematologic cancers,syndromes of bone marrow failure, and congenital disorders ofthe lymphohematopoietic system1,2. This type of treatment, however,has largely been restricted to patients with an HLA-identicalfamily member who is willing to be a donor3. To extend marrowtransplantation to patients who could benefit from an allogeneicmarrow transplant, but who lack a suitably HLA-matched relateddonor, several investigators have explored the use of othersources of marrow, including partially HLA-matched family membersand unrelated donors who are phenotypically, but not genotypically,closely matched for HLA-A, B, and DR antigens. The first transplantationsinvolving unrelated donors were reported in the mid-1970s,4,5,6,7,8,9and several other reports followed10,11,12,13,14,15,16,17,18,19,20,21,22.The use of marrow from closely HLA-matched unrelated donorshas been limited by the lack of accessible donor registriesof sufficient size to permit identification of an appropriatedonor23,24,25,26,27,28. In 1986 the National Marrow Donor Program(NMDP) was established in the United States to facilitate donorsearches and marrow procurement for patients lacking an HLA-identicalrelated donor29. In this report we present the results of 462marrow transplantations performed between December 1987 andNovember 1990 with unrelated donors identified through the program.
Methods
The NMDP
The NMDP was established in 1986 through a contract from theU.S. Navy to the American Red Cross. Responsibility for thecontract was transferred to the National Heart, Lung, and BloodInstitute in February 1989. The procedure and policies of theNMDP have been described previously29.
Patients
The study population consisted of 462 patients with malignantor nonmalignant diseases who received marrow transplants atcenters in the United States between December 16, 1987, andNovember 3, 1990 (Table 1 and Table 2). Among the patients withleukemia, those projected to have a good outcome after transplantationincluded patients with acute leukemia in first or second completeremission and those with chronic myelogenous leukemia in theprimary chronic phase. Patients with acute leukemia in morethan second remission or in relapse and patients with chronicmyelogenous leukemia in secondary or a more advanced chronicphase or in accelerated or blastic phase were considered tobe at high risk. The infusion of marrow from an unrelated donorwas the second transplantation procedure for six patients, andseven patients received two marrow transplants from unrelatedNMDP donors.
Table 2. Characteristics of the Donors and Recipients.
Patients received a variety of preparative regimens determinedby the individual transplantation centers and based on requirementsfor the treatment of the specific underlying disease. Of the352 patients with leukemia, 306 (87 percent) received total-bodyirradiation and chemotherapy. Seventy percent of the patientswith marrow-failure syndromes received total-body irradiation.Twenty-nine of the 41 patients with congenital disorders weretreated with chemotherapy alone.
Methods for the prophylactic treatment of graft-versus-hostdisease (GVHD) varied according to the transplantation center.Ninety-five patients (21 percent) received marrow depleted ofdonor 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. Thematching of donors and recipients was based on HLA serotypingperformed according to standard techniques30. A mismatch ofone antigen was categorized as minor if the mismatched antigenwas 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-twocollection facilities performed the marrow harvests; five centersharvested marrow from more than 25 donors each. The transportedmarrow was infused without manipulation in 215 patients (47percent), whereas in 247 (53 percent) it was manipulated forthe following reasons: volume reduction (13 patients, 3 percent),red-cell depletion for ABO incompatibility (139 patients, 30percent), T-cell depletion for the prevention of GVHD (67 patients,15 percent), or both ABO incompatibility and the preventionof GVHD (28 patients, 6 percent).
Data Collection
The transplantations were performed at 28 centers in the UnitedStates: 21 (75 percent) of the centers performed 1 to 9 transplantations,1 center performed 12 procedures, 1 center 19 procedures, and5 centers more than 25 primary transplantations (27, 36, 56,83, and 129 procedures). The median length of follow-up was1.5 years (range, 0.3 to 3.7). Data on survival were gathereduntil September 1, 1991, in all but two transplantation centers,in which the cutoff date was March 1, 1991. We considered thatall patients were suitable for evaluation for engraftment, acuteGVHD, and chronic GVHD. The day of engraftment was defined asthe first of three consecutive days on which the neutrophilcount exceeded 500 per cubic millimeter. Thus, patients in whomengraftment did not occur did not have a neutrophil count ofmore than 500 per cubic millimeter for three consecutive daysat any time after transplantation. Patients with initial engraftmentin whom severely hypocellular marrow or an absolute neutrophilcount of less than 500 per cubic millimeter recurred were consideredto have secondary graft failure. The stage of involvement ofthe skin, liver, and intestine with acute GVHD was measuredindividually according to standard criteria,31 and a grade wasassigned on the basis of the sum of the individual stages: agrade of 0 was assigned for a score of 0; a grade of I for ascore of 1 to 2; a grade of II for a score of 3 to 4, exceptin cases in which the skin, liver, or intestine alone was consideredto 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 GVHDwas assessed as limited (mild skin involvement only) or extensive(skin, liver, and intestinal involvement).
Statistical Analysis
Disease-free survival curves were calculated by Kaplan-Meieranalysis32. The length of time from the first transplantationto an event was defined in three ways: as the interval betweentransplantation and relapse among patients who were reportedto be free of their disease after transplantation, as the intervalfrom transplantation to day 28 among patients who survived atleast 28 days but were never free of their disease after transplantation,or as the interval between transplantation and death among patientswho did not fit into the first two categories. In univariateanalyses, the log-rank statistic33 was determined, and its levelof significance is given. All values reflect two-sided P values.The two-year disease-free survival rates and their 95 percentconfidence intervals are given. In multivariate analyses involvingthe occurrence of disease-free survival and relapse among patientswith leukemia, the proportional-hazards model34 was used withthe following covariates: recipient's age, recipient's cytomegalovirusstatus, the level of HLA matching (a disparity of 0 or 1 antigen),donor's age, donor's sex, the need to manipulate marrow to preventGVHD, the interval between diagnosis and transplantation, thetype of leukemia (chronic vs. acute), and leukemia status (goodvs. poor prognostic factors). Only variables whose coefficientshad P values of 0.10 are reported.
For nonfatal events, such as engraftment, the occurrence ofgrade II to IV or grade III to IV acute GVHD, or the occurrenceof extensive chronic GVHD, death was defined as a censored variablein the life-table analyses. The censoring date for the analysisinvolving nonfatal events was the date of the last regular follow-upvisit or the date of death. Both Kaplan-Meier and proportional-hazardsmodels were employed. The following independent variables wereconsidered for these dependent variables: recipient's age, recipient'scytomegalovirus status, the level of HLA matching, the use ofT-cell-depleted marrow to prevent GVHD, and a diagnosis of chronicrather than acute myelogenous leukemia. An independent variableappearing in several proportional-hazards models was alwayscoded in the same way, and only the variables whose coefficientshad P values of 0.10 are reported. Results are given as theprobability 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 froma donor serologically matched for HLA-A, B, and DR antigens,whereas 61 (13 percent) received marrow with a minor mismatchof one HLA antigen and 92 (20 percent) received marrow witha major mismatch of one class I or class II HLA antigen. Inthree cases (1 percent) there was a mismatch of more than oneHLA antigen. The median interval between the initiation of apreliminary search for a donor and marrow transplantation was196 days (range, 17 to 1037). For patients with chronic myelogenousleukemia, the median interval was 252 days (range, 50 to 1037).For patients with other diagnoses, the median interval was 164days (range, 17 to 709).
Engraftment
The probability of engraftment by 100 days after transplantationwas 0.94 ±0.03 (95 percent confidence interval, 0.91to 0.97); engraftment occurred a median of 22 days after transplantation(range, 6 to 84). On multivariate analysis, an accelerated rateof engraftment was independently associated with the receiptof marrow depleted of T cells (P<0.001), the receipt of HLA-matchedmarrow (P<0.001), and increasing patient age (P = 0.05).
Eight percent of the patients had graft failure between 25 and263 days after transplantation. Among the variables examined,only the use of marrow depleted of T cells was significantlyassociated with secondary graft failure after initial engraftment(0.14 ±0.08 vs. 0.07 ±0.04, P = 0.04). One yearafter transplantation, 11 of 143 patients whose transfusionhistory could be evaluated continued to require transfusionsof platelets (2 patients), red cells (2), or both (7).
GVHD
The probability of having grade II, III, or IV acute GVHD by100 days after transplantation was 0.64 ±0.05 (95 percentconfidence interval, 0.59 to 0.69), and a substantial numberof the patients with GVHD had severe (grade III to IV) acuteGVHD (0.47 ±0.06) (Figure 1A). Multivariate analysisshowed that the development of grade III to IV acute GVHD wasindependently associated with the use of marrow that had notbeen depleted of T cells (P<0.001) (Figure 1B) and increasingpatient age (P = 0.001) (Figure 1C). The development of acuteGVHD was not associated with the level of HLA disparity, asdefined by serologic analysis (Figure 1D).
Figure 1. Probability of Acute GVHD in All Patients (Panel A) and Probability of Grade III to IV Acute GVHD, According to Whether the Patients Received T-Cell-Depleted Marrow (Panel B), Their Age (Panel C), and Whether They Received HLA-Matched or HLA-Mismatched Marrow (Panel D).
The P values reflect the results of univariate analysis.
The probability of limited or extensive chronic GVHD one yearafter transplantation was 0.55 ±0.07, whereas that ofextensive chronic GVHD alone was 0.35 ±0.07 (Figure 2).Multivariate analysis showed that the development of extensivechronic GVHD was significantly associated with the use of marrowthat had not been depleted of T cells (P = 0.001) and with adiagnosis of chronic myelogenous leukemia (P<0.001). Univariateanalysis indicated that extensive chronic GVHD correlated withincreasing patient age; however, no such correlation was foundon multivariate analysis, since the patients with chronic myelogenousleukemia were older (Table 1) and the diagnosis of chronic myelogenousleukemia was found to be the significant independent variable,rather than patient age.
Figure 2. Probability of Limited or Extensive Chronic GVHD and of Extensive Chronic GVHD Alone in All Patients.
Survival
Patients with Leukemia
The patients with leukemia were followed for a median of 1.5years (range, 0.72 to 3.7). The probability of disease-freesurvival at two years among patients with leukemia and goodprognostic factors was 0.40 ±0.08, whereas it was 0.19±0.06 (P<0.001) among patients with leukemia and poorprognostic factors. Among patients with acute leukemia in firstor second remission, the probability of disease-free survivalwas 0.45 ±0.13, which was superior to that among patientswith more advanced disease (0.19 ±0.08, P<0.001).Similarly, among patients with chronic myelogenous leukemiain the primary chronic phase, the disease-free survival at twoyears was 0.37 ±0.10, which was higher than that amongpatients with more advanced disease (0.21 ±0.09, P =0.02). Although these results suggest that patients with acuteleukemia had a more favorable probability of disease-free survivalthan patients with chronic leukemia, multivariate analysis inwhich recipient's age was included as a variable indicated thereverse (P = 0.02). Several variables were examined by multivariateanalysis for their effect on the survival of patients with leukemia.Those found to be significant are presented in Table 3. Seventyof the 352 patients with leukemia received marrow depleted ofT cells. There was a trend (P = 0.10) toward improved disease-freesurvival among these patients. Considering the results of multivariateanalysis, it is not surprising that patients under the age of18 years who had good prognostic factors for leukemia did wellafter transplantation. Among 41 such patients, the probabilityof disease-free survival at two years was 0.53 ±0.15.In contrast, the probability of disease-free survival amongpatients over the age of 18 who had poor prognostic factorsfor leukemia was 0.11 ±0.06 (Figure 3).
Figure 3. Probability of Disease-free Survival, According to Prognostic Factors for Leukemia and Age.
The probability of relapse within two years after transplantationamong all patients with leukemia was 0.19 ±0.06. Thepatients over 18 years of age who had acute leukemia were atgreatest risk for relapse (Figure 4). The risk variables, asdetermined by multivariate analysis, that were associated withrelapse included older age (P = 0.001), acute leukemia as opposedto chronic leukemia (P = 0.03), HLA mismatch (P<0.001), positivecytomegalovirus-antibody status among recipients (P = 0.04),and the use of marrow that had not been depleted of T cells(P = 0.009). The use of marrow depleted of T cells appearedprimarily to delay relapse rather than to reduce the relapserate.
Figure 4. Probability of Relapse after Transplantation, According to Type of Leukemia and Age.
Patients with Myelodysplasia or Aplastic Anemia
The median interval from diagnosis to transplantation was 0.9year (range, 0.2 to 8.2) among patients with aplastic anemiaand 0.9 year (range, 0.3 to 10.3) among patients with myelodysplasia.The probability of survival at two years was 0.29 ±0.17among patients with aplastic anemia or paroxysmal nocturnalhemoglobinuria (Figure 5). However, 4 of the 10 patients withaplasia who were alive one year after transplantation continuedto require transfusions of platelets (2 patients), red cells(1), or both (1). Although the probability of survival amongpatients with myelodysplasia was 0.24 ±0.15, not allpatients were disease-free. The probability of disease-freesurvival at two years was 0.18 ±0.14 (Figure 5).
Figure 5. Probability of Survival among Patients with Aplastic Anemia or Paroxysmal Nocturnal Hemoglobinuria and Patients with Myelodysplasia.
Patients with Congenital Disorders
Forty-one patients received a transplant for the treatment ofa congenital disorder reported to be amenable to therapy withmarrow from an HLA-identical sibling35. The immunodeficiencydisorders included combined immunodeficiency syndromes (9 patients),Wiskott-Aldrich syndrome (5), T-cell deficiency (2), commonvariable immunodeficiency (2), ataxia-telangiectasia (2), andleukocyte-adhesion deficiency (1). Among the patients treatedfor non-immunodeficiency congenital disorders, the majorityhad Hurler's syndrome (10). Other diagnoses included Sanfilippo'ssyndrome (2 patients), globoid leukodystrophy (2), Fanconi'sanemia (1), osteopetrosis (1), Hunter's syndrome (1), Gaucher'sdisease (1), and familial erythrophagocytic lymphohistiocytosis(2). In this group of patients, the probability of engraftmentwithin 100 days after transplantation was 0.96 ±0.07,whereas the probability of having grade II, III, or IV acuteGVHD within 100 days was 0.37 ±0.17. The probabilityof having extensive chronic GVHD at one year was 0.08 ±0.11.Because of the nature of these diseases, it is not currentlypossible to address whether these patients were disease-freeafter transplantation. However, the probability of survivalamong 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). Thispatient was only 2.6 years of age at the time of transplantationand did not have severe acute or chronic GVHD, whereas the otherpatients were all over the age of 35 years and either died soonafter transplantation (day 3) or had severe (grade III) acuteGVHD and died within 120 days after transplantation. The patientwith 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 oldat transplantation, died of grade III acute GVHD 114 days aftertransplantation.
Patients Who Received Second Transplants
Five of the six patients whose NMDP-facilitated transplant wastheir second transplant had received an autologous transplantfor the treatment of acute leukemia or lymphoma (acute lymphoblasticleukemia in one, non-Hodgkin's lymphoma in one, and acute nonlymphocyticleukemia in three). One of these five patients was alive morethan 400 days after transplantation, and another 1150 days aftertransplantation. The sixth patient had received a transplantfor the treatment of aplastic anemia 1 month earlier from anunrelated donor identified through the Anthony Nolan Registryin England, and he died 70 days after receiving his second transplant.
Seven patients received a second marrow graft from an unrelateddonor identified through the NMDP because of primary failureof the marrow to engraft or secondary graft failure after theirfirst transplantation. The same donor was used for only oneof these patients. Three had received marrow that had not beendepleted of T cells, and four received marrow that had beendepleted of T cells. The median interval between the first andsecond transplantations was 64 days (range, 55 to 464). Oneof the seven patients survived. This patient (who had chronicmyelogenous leukemia in chronic phase) received an infusionof cryopreserved autologous marrow when his second marrow infusionfrom an unrelated donor failed to engraft.
Complications and Causes of Death
One hundred thirty-eight patients (30 percent) had interstitialpneumonia, 109 (24 percent) were reported to have had hepaticdysfunction consistent with venoocclusive disease, 35 (8 percent)to have had cardiac failure, and 8 (2 percent) to have had aB-cell lymphoproliferative disorder. Lymphoproliferative disorderswere observed among patients who received marrow depleted ofT cells (5 patients [5 percent]) as well as those who did not(3 patients [1 percent]). Furthermore, lymphoproliferative disorderswere observed among patients who did not have acute GVHD (3of 213 patients) as well as among those who did (5 of 249 patients).
Of the 462 patients, 307 (66 percent) have died. The primaryand secondary causes of death are listed in Table 4.
Table 4. Primary and Secondary Causes of Death after Transplantation in 307 Patients.
The latest Karnofsky score was evaluated in 145 patients whosurvived at least one year. Ninety-nine (68 percent) had a performancescore of 90 or 100, whereas 11 (8 percent) had a score of 80,14 (10 percent) had a score between 20 and 70, and 21 (14 percent)had died after one year. Neither the age of the recipients northe degree of HLA matching influenced these scores.
Discussion
Transplantation of bone marrow from an HLA-identical siblingresults in prolonged leukemia-free survival in approximately50 percent of patients with good prognostic factors and in upto 20 percent of patients with advanced leukemia1,2,36,37. Thesurvival rate among patients with aplastic anemia is 50 to 80percent for patients receiving HLA-identical grafts,38 and disease-freesurvival among patients with myelodysplasia ranges from 30 to50 percent39. Several studies of marrow transplantation withrelated donors other than genotypically HLA-identical siblingsindicate that the probability of having serious complicationsafter transplantation, including graft failure, acute and chronicGVHD, fatal infections, and lymphoproliferative disorders, isincreased as compared with that observed after the transplantationof marrow from an HLA-identical sibling and is higher amongrecipients of grafts that are not matched for two or three HLAloci 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 to55 recipients who received marrow from closely HLA-matched unrelateddonors indicate that both the incidence and the severity ofcomplications may be increased in these patients12,13,15,17,18,19,20,21,22.
The probability of graft failure after an infusion of marrowfrom a family member correlates with the degree of HLA incompatibility41,45,50and the use of T-cell depletion to prevent acute and chronicGVHD21,50,51,52. In the present NMDP study of 462 patients,graft failure was evaluated by calculating the probability ofboth initial myeloid engraftment and secondary marrow failure.The probability of engraftment for the entire study populationwas lower than that reported by Beatty et al.22 but similarto that reported by Ash et al.,21 who used in vitro T-cell depletionto prevent GVHD. In our study the probability of engraftmentwithin 100 days after transplantation was 0.94 ±0.03,with an accelerated rate of engraftment independently associatedwith the receipt of marrow depleted of T cells and with thereceipt of HLA-matched marrow. The difference in the lengthof time to engraftment between marrow depleted of T cells andunmanipulated marrow may be due to factors other than the useof T-cell-depleted marrow, such as the use of post-transplantationchemoprophylaxis regimens that include intravenous methotrexate,which would be expected to delay engraftment. Transplantationcenters that used in vitro T-cell depletion to prevent GVHDdid not use methotrexate, but rather used corticosteroids, cyclosporine,and antithymocyte globulin. In contrast, most centers that infusedunmodified marrow used methotrexate to prevent GVHD after transplantation.
The probability of severe acute GVHD was higher in our patientsthan in recipients of marrow from HLA-matched siblings; theprobability of having grade II, III, or IV acute GVHD was 0.64±0.05. This high probability is comparable to that observedamong recipients of unmanipulated marrow mismatched for oneor two HLA antigens from a family member22,41. Yet in our seriesthe level of donor-recipient HLA disparity, as evaluated byserotyping, did not affect the probability of the developmentof acute GVHD. This probably reflects the fact that phenotypicallyHLA-identical unrelated pairs of donors and recipients haveimportant differences in structural polymorphisms that are notdetectable by conventional serotyping for HLA-A, B, and DR alloantigens.These differences can be detected in the HLA class I regionby one-dimensional isoelectric focusing53,54,55 and in the classII region by restriction-fragment-length polymorphism56,57 andhybridization with sequence-specific oligonucleotide probes56,58,59,60.In the present study, in which 272 donor-recipient pairs hadinterpretable results of mixed-lymphocyte culture, there wasno correlation between the level of reactivity and the incidenceor severity of acute GVHD (data not shown).
Despite the increased risk of graft failure and severe acuteand chronic GVHD, this study demonstrates in a large patientpopulation that the transplantation of marrow from unrelateddonors can be an effective treatment for certain hematologiccancers and non-neoplastic disorders. Among 352 patients withleukemia, the probability of disease-free survival at two yearswas 0.40 ±0.08 for patients with good prognostic factorsand 0.19 ±0.06 for patients with poor prognostic factors.Post-transplantation relapse is a serious problem for recipientsof marrow from HLA-identical siblings, with patients who undergotransplantation while in relapse at the highest risk61. In ourstudy, the stage of disease was not associated with the riskof relapse, but it was associated with the risk of death.
Although recipients of HLA-identical marrow depleted of T cellsfor the treatment of advanced leukemia or chronic myelogenousleukemia are at increased risk of relapse after transplantation,62,63recipients of T-cell-depleted marrow from unrelated donors donot appear to be at a similar increased risk for relapse. Thelow probability of relapse in the NMDP patient population isencouraging and suggests that transplants from unrelated donorsmay offer a considerable graft-versus-leukemia effect. However,the effect of other factors reported to influence the probabilityof post-transplantation relapse, including the pretransplantationpreparative regimen, the presence of GVHD, and post-transplantationimmunosuppression,61,64,65,66 has not been examined, and a longerfollow-up is necessary for a definitive analysis of relapsein this patient population.
Seventy of the 352 patients with leukemia received marrow depletedof T cells for the prevention of acute and chronic GVHD. Theuse of T-cell-depleted marrow was associated with more rapidengraftment, a decrease in the incidence and severity of GVHD,and a reduction in the mortality rate by approximately 60 percentduring the first 50 days after transplantation. Thereafter,there was no difference in survival among patients with leukemiawho received T-cell-depleted marrow and those who received unmanipulatedmarrow. Since this initial analysis does not reveal an increasein relapse among recipients of T-cell-depleted marrow, it isunclear why the leukemia-free survival rate was only marginallyimproved for these patients as determined by multivariate analysis(P = 0.10). The effects of T-cell depletion in our study shouldbe interpreted cautiously, however, since only 5 of the 28 transplantationcenters used this approach to prevent GVHD, and T-cell depletionmay be a marker for the effects of the complete regimen or anyone of the components of the regimen used for the marrow procedure.Nevertheless, the finding is similar to that observed in a retrospectivereview that analyzed the effect of T-cell depletion on the outcomeof marrow transplantation from related donors other than HLA-identicalsiblings50.
For young adults who have an HLA-matched family member, bonemarrow transplantation is the preferred treatment for severeaplastic anemia38,67,68. HLA-incompatible family members orclosely matched unrelated persons have donated marrow to patientslacking an HLA-identical sibling16,17,20,69. In the presentstudy, patients with aplastic anemia generally had poor prognosticcharacteristics70. All patients had received multiple bloodtransfusions, and there was a relatively long interval betweendiagnosis and transplantation. However, the probability of survivalafter 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 involvingunrelated donors, it is likely that these patients had not respondedto immunosuppressive or cytokine therapy.
Approximately 50 to 60 percent of patients with myelodysplasiawho are under the age of 30 years are disease-free three yearsafter the transplantation of marrow from HLA-matched siblings,whereas the probability of disease-free survival is only 25percent among patients over the age of 3039,71,72,73. When comparedwith the results of the transplantation of marrow from HLA-identicalsiblings, the results of the 32 procedures involving marrowfrom 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 subgroupswas not skewed toward advanced disease; only 11 of the 32 patientshad excess blasts. Thus, neither older age nor advanced diseaseaccounted for the poor outcome.
Recipients of partially matched transplants from family membersare at higher risk for infectious complications and lymphoproliferativedisorders than are recipients of transplants from HLA-identicalsiblings46,48. This observation has been extended to recipientsof marrow from unrelated donors15,21 and is true of the presentstudy, in which infection, interstitial pneumonia, or both contributedto 58 percent of the deaths and in which secondary lymphoproliferativedisorders developed in eight patients.
Although the optimal approaches to the selection of an unrelateddonor and the prevention of graft failure and acute and chronicGVHD remain to be defined, this report demonstrates that transplantationwith marrow derived from an unrelated donor can benefit manypatients.
We are indebted to Ms. Patricia Coppo and her staff of donor-searchcoordinators at the NMDP, to Ms. Jessie Song and Ms. Qin Tianfor computer-programming support, and to Ms. Carolynn Barnesfor 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
Thomas ED. Karnofsky memorial lecture: marrow transplantation for malignant diseases. J Clin Oncol 1983;1:517-531. [Free Full Text]
O'Reilly RJ. Allogeneic bone marrow transplantation: current status and future directions. Blood 1983;62:941-964. [Free Full Text]
Bortin MM, Rimm AA. Increasing utilization of bone marrow transplantation: II. Results of the 1985-1987 survey. Transplantation 1989;48:453-458. [Medline]
Horowitz SD, Groshong T, Bach FH, Hong R. Treatment of severe combined immunodeficiency with bone-marrow from an unrelated, mixed-leucocyte-culture-nonreactive donor. Lancet 1975;2:431-433. [Medline]
O'Reilly RJ, Dupont B, Pahwa S, et al. Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. N Engl J Med 1977;297:1311-1318. [Abstract]
The Westminster Hospitals Bone-Marrow Transplant Team. Bone-marrow transplant from an unrelated donor for chronic granulomatous disease. Lancet 1977;1:210-213. [CrossRef][Medline]
Speck B, Zwaan FE, van Rood JJ, Eernisse JG. Allogeneic bone marrow transplantation in a patient with aplastic anemia using a phenotypically HL-A-identical unrelated donor. Transplantation 1973;16:24-28. [CrossRef][Medline]
Lohrmann H-P, Dietrich M, Goldmann SF, et al. Bone marrow transplantation for aplastic anaemia from a HL-A and MLC-identical unrelated donor. Blut 1975;31:347-354. [CrossRef][Medline]
Hansen JA, Clift RA, Thomas ED, Buckner CD, Storb R, Giblett ER. Transplantation of marrow from an unrelated donor to a patient with acute leukemia. N Engl J Med 1980;303:565-567. [Medline]
Gordon-Smith EC, Fairhead SM, Chipping PM, et al. Bone-marrow transplantation for severe aplastic anaemia using histocompatible unrelated volunteer donors. BMJ 1982;285:835-837.
Duquesnoy RJ, Zeevi A, Marrari M, Hackbarth S, Camitta B. Bone marrow transplantation for severe aplastic anemia using a phenotypically HLA-identical, SB-compatible unrelated donor. Transplantation 1983;35:566-571. [Medline]
Hows JM, Yin JL, Marsh J, et al. Histocompatible unrelated volunteer donors compared with HLA nonidentical family donors in marrow transplantation for aplastic anemia and leukemia. Blood 1986;68:1322-1328. [Free Full Text]
Howard MR, Hows JM, Gore SM, et al. Unrelated donor marrow transplantation between 1977 and 1987 at four centers in the United Kingdom. Transplantation 1990;49:547-553. [Medline]
McGlave P, Scott E, Ramsay N, et al. Unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia. Blood 1987;70:877-881. [Free Full Text]
Gingrich RD, Ginder GD, Goeken NE, et al. Allogeneic marrow grafting with partially mismatched, unrelated marrow donors. Blood 1988;71:1375-1381. [Free Full Text]
Bacigalupo A, Hows J, Gordon-Smith EC, et al. Bone marrow transplantation for severe aplastic anemia from donors other than HLA identical siblings: a report of the BMT Working Party. Bone Marrow Transplant 1988;3:531-535. [Medline]
Camitta B, Ash R, Menitove J, et al. Bone marrow transplantation for children with severe aplastic anemia: use of donors other than HLA-identical siblings. Blood 1989;74:1852-1857. [Free Full Text]
McGlave PB, Beatty P, Ash R, Hows JM. Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases. Blood 1990;75:1728-1732. [Erratum, Blood 1990;76:654.] [Free Full Text]
Mackinnon S, Hows JM, Goldman JM, et al. Bone marrow transplantation for chronic myeloid leukemia: the use of histocompatible unrelated volunteer donors. Exp Hematol 1990;18:421-425. [Medline]
Gajewski JL, Ho WG, Feig SA, Hunt L, Kaufman N, Champlin RE. Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure. Transplantation 1990;50:244-249. [Medline]
Ash RC, Casper JT, Chitambar CR, et al. Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors. N Engl J Med 1990;322:485-494. [Abstract]
Beatty PG, Hansen JA, Longton GM, et al. Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies. Transplantation 1991;51:443-447. [Medline]
McCullough J. Bone marrow transplantation from unrelated volunteer donors: summary of a conference on scientific, ethical, legal, financial, and other practical issues. Transfusion 1982;22:78-81. [Medline]
McCullough J, Rogers G, Dahl R, et al. Development and operation of a program to obtain volunteer bone marrow donors unrelated to the patient. Transfusion 1986;25:315-323. [CrossRef]
McElligott MC, Menitove JE, Aster RH. Recruitment of unrelated persons as bone marrow donors: a preliminary experience. Transfusion 1986;26:309-314. [Medline]
Bradley B, Bidwell JL, Jarrold EA, Goffin RB, Klouda PT. HLA matched unrelated bone marrow transplants: a proposal to speed up donor selection using a DNA bank. Bone Marrow Transplant 1986;1:146-147.
Raffoux C, Gluckman E, Busson M, Prevost P. Development of a national volunteer donor's file for bone marrow transplantation. Bone Marrow Transplant 1988;3:Suppl I:163-164.
Beatty PG, Dahlberg S, Mickelson EM, et al. Probability of finding HLA-matched unrelated marrow donors. Transplantation 1988;45:714-718. [Medline]
McCullough J, Hansen J, Perkins H, Stroncek D, Bartsch G. Establishment of the National Bone Marrow Donor Registry. In: Gale RP, Champlin RE, eds. Bone marrow transplantation: current controversies. Vol. 91 of UCLA Symposia on Molecular and Cellular Biology, new series. New York: Alan R. Liss, 1989:641-58.
Hopkins KA. Basic microlymphocytotoxicity test. In: Zachary AA, Teresi GA, eds. Laboratory manual. 2nd ed. Lenexa, Kans.: American Society for Histocompatibility and Immunogenetics, 1990:195-201.
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974;18:295-304. [Medline]
Kaplan EL, Meier P. Nonparametic estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163-170. [Medline]
Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
O'Reilly RJ, Brochstein J, Dinsmore R, Kirkpatrick D. Marrow transplantation for congenital disorders. Semin Hematol 1984;21:188-221. [Medline]
Brochstein JA, Kernan NA, Groshen S, et al. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med 1989;317:1618-1624. [Abstract]
Santos GW, Kaizer H. Bone marrow transplantation in acute leukemia. Semin Hematol 1982;19:227-239. [Medline]
Storb R, Thomas ED, Buckner CD, et al. Marrow transplantation for aplastic anemia. Semin Hematol 1984;21:27-35. [Medline]
Appelbaum FR, Barrall J, Storb R, et al. Bone marrow transplantation for patients with myelodysplasia: pretreatment variables and outcome. Ann Intern Med 1990;112:590-597.
Powles RL, Morgenstern GR, Kay HEM, et al. Mismatched family donors for bone-marrow transplantation as treatment for acute leukemia. Lancet 1983;1:612-615. [CrossRef][Medline]
Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985;313:765-771. [Abstract]
Bozdech MJ, Sondel PM, Trigg ME, et al. Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection. Exp Hematol 1985;13:1201-1210. [Medline]
Cahn JY, Herve P, Flesch M, et al. Marrow transplantation from HLA non-identical family donors for the treatment of leukaemia: a pilot study of 15 patients using additional immunosuppression and T-cell depletion. Br J Haematol 1988;69:345-349. [Medline]
Kernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia: identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation 1987;43:842-847. [Medline]
Anasetti C, Amos D, Beatty PG, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med 1989;320:197-204. [Abstract]
Shapiro RS. Epstein-Barr virus-associated B-cell lymphoproliferative disorders in immunodeficiency: meeting the challenge. J Clin Oncol 1990;8:371-373. [Medline]
Sondel PM, Hank JA, Trigg ME, et al. Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: autologous marrow recovery with specific immune sensitization to donor antigens. Exp Hematol 1986;14:278-286. [Medline]
Atkinson K, Farewell V, Storb R, et al. Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. Blood 1982;60:714-720. [Free Full Text]
Bunin NJ, Casper JT, Chitambar C, et al. Partially matched bone marrow transplantation in patients with myelodysplastic syndromes. J Clin Oncol 1988;6:1851-1855. [Abstract]
Ash RC, Horowitz MM, Gale RP, et al. Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion. Bone Marrow Transplant 1991;7:443-452. [Medline]
O'Reilly RJ, Collins NH, Kernan NA, et al. Transplantation of marrow-depleted T cells by soybean lectin agglutination and E-rosette depletion: major histocompatibility complex-related graft resistance in leukemic transplant recipients. Transplant Proc 1985;17:455-459.
Trigg ME, Billing R, Sondel PM, et al. Clinical trial depleting T lymphocytes from donor marrow for matched and mismatched allogeneic bone marrow transplants. Cancer Treat Rep 1985;69:377-386. [Medline]
Choo SY, Antonelli P, Nisperos B, Nepom GT, Hansen JA. Six variants of HLA-B27 identified by isoelectric focusing. Immunogenetics 1986;23:24-29. [Medline]
Vasilov RG, Hahn A, Molders H, van Rood JJ, Breuning M, Ploegh HL. Analysis of human class I antigens by two-dimensional gel electrophoresis. Immunogenetics 1983;17:333-356. [Medline]
Neefjes JJ, Breur-Vriesendorp BS, van Seventer GA, Ivanyi P, Ploegh HL. An improved biochemical method for the analysis of HLA-class I antigens: definition of new HLA-class I subtypes. Hum Immunol 1986;16:169-181. [CrossRef][Medline]
Clay TM, Bidwell JL, Howard MR, Bradley BA. PCR-fingerprinting for selection of HLA matched unrelated marrow donors. Lancet 1991;337:1049-1052. [CrossRef][Medline]
Noreen HJ, Davidson ML, McCullough J, Bach FH, Segall M. HLA class II typing by restriction fragment length polymorphism (RFLP) in unrelated bone marrow transplant patients. Transplant Proc 1989;21:2968-2970. [Medline]
Baxter-Lowe LA, Eckels DD, Ash R, Casper J, Hunter JB, Gorski J. Future directions in selection of donors for bone marrow transplantation: role of oligonucleotide genotyping. Transplant Proc 1991;23:1699-1700. [Medline]
Angelini G, de Preval C, Gorski J, Mach B. High-resolution analysis of the human HLA-DR polymorphism by hybridization with sequence-specific oligonucleotide probes. Proc Natl Acad Sci U S A 1986;83:4489-4493. [Erratum, Proc Natl Acad Sci U S A 1986;83:6664.] [Free Full Text]
Tiercy JM, Morel C, Freidel AC, et al. Selection of unrelated donors for bone marrow transplantation is improved by HLA class II genotyping with oligonucleotide hybridization. Proc Natl Acad Sci U S A 1991;88:7121-7125. [Free Full Text]
Buckner CD, Clift RA, Appelbaum FR, et al. Effects of treatment regimens on post marrow transplant relapse. Semin Hematol 1991;28:32-34. [Medline]
McGlave P. Bone marrow transplants in chronic myelogenous leukemia: an overview of determinants of survival. Semin Hematol 1990;27:23-30. [Medline]
Goldman JM, Gale RP, Horowitz MM, et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk for relapse associated with T-cell depletion. Ann Intern Med 1988;108:806-814.
Clift RA, Buckner CD, Appelbaum FR, et al. Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two irradiation regimens. Blood 1991;77:1660-1665. [Free Full Text]
Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED, Seattle Marrow Transplant Team. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981;304:1529-1533. [Medline]
Sullivan KM, Weiden PL, Storb R, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 1989;73:1720-1728. [Erratum, Blood 1989;74:1180.] [Free Full Text]
Sanders JE, Whitehead J, Storb R, et al. Bone marrow transplantation experience for children with aplastic anemia. Pediatrics 1986;77:179-186. [Free Full Text]
Casper JT, Truitt RR, Baxter-Lowe LA, Ash RC. Bone marrow transplantation for severe aplastic anemia in children. Am J Pediatr Hematol Oncol 1990;12:434-448. [Medline]
Gordon BG, Strandjord SE, Warkentin PI, Kadushin J, Coccia PF. Successful treatment of severe aplastic anemia by bone marrow transplantation from HLA nonidentical family members: preliminary results utilizing cyclophosphamide and 600 cGY fractionated total body irradiation. Am J Pediatr Hematol Oncol 1991;13:29-33. [Medline]
Champlin RE, Horowitz MM, van Bekkum DW, et al. Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Blood 1989;73:606-613. [Free Full Text]
Longmore G, Guinan EC, Weinstein HJ, Gelber RD, Rappeport JM, Antin JH. Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia. J Clin Oncol 1990;8:1707-1714. [Abstract]
De Witte T, Zwaan F, Gratwohl A, et al. Timing of marrow transplantation in secondary leukemias and myelodysplastic syndromes. Transplant Proc 1989;21:2958-2959. [Medline]
Guinan EC, Tarbell NJ, Tantravahi R, Weinstein HJ. Bone marrow transplantation for children with myelodysplastic syndromes. Blood 1989;73:619-622. [Free Full Text]
Appendix
The following centers participated in the National Marrow DonorProgram: Transplantation centers: Fred Hutchinson Cancer ResearchCenter; University of Minnesota Hospital and Clinic; UCLA; MedicalCollege 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 AffairsMedical Center; City of Hope National Medical Center; Universityof 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-Universityof Pittsburgh; Children's-Brigham and Women's Hospital TransplantUnit; Children's Hospital of Los Angeles; Wayne State University-HarperHospitals; Vanderbilt University Medical Center; Children'sHospital Medical Center, Cincinnati; All Children's Hospital,St. Petersburg; Children's Hospital of Philadelphia; Universityof California, San Francisco, Pediatric Bone Marrow TransplantationProgram; Johns Hopkins Oncology Center; and University of SouthernFlorida; Donor centers: Blood Center of Southeastern Wisconsin;American Red Cross, St. Paul Region; Puget Sound Blood Center;Sacramento Medical Foundation Blood Center; Heart of AmericaBone Marrow Donor Registry; National Institutes of Health MarrowDonor Center; American Red Cross Central California Region,San Jose; American Red Cross, Greater Upstate New York Region,Albany Site; Central Indiana Regional Blood Center; AmericanRed Cross Los Angeles-Orange Counties Region; Europdonor Foundation;American Red Cross, Carolinas Region; American Red Cross, Penn-JerseyRegion; American Red Cross, Pacific Northwest Region; AmericanRed Cross, Great Lakes Region; American Red Cross, NorthwestOhio Region; San Diego Blood Bank; Blood Center at Wadley Institutes;Greater New York Blood Program; Community Blood Bank; AmericanRed Cross, Detroit; American Red Cross, Rochester; AmericanRed Cross, Burlington; American Red Cross, Madison; AmericanRed Cross, Baltimore; Civitan Regional Blood Center; FloridaReference Labs; American Red Cross, Dedham; American Red Cross,Fort Wayne; American Red Cross, Columbus; Johns Hopkins HemapheresisCenter; Irwin Memorial Blood Bank; Stanford University BloodCenter; Blood Bank, San Bernardino-Riverside; American Red Cross,Farmington; American Red Cross, Atlanta; American Red Cross,Wichita; American Red Cross, Syracuse; Central Blood Bank; AmericanRed 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 BloodCenter; and New Jersey HLA Registry Foundation; Collection centers:University of Minnesota Hospital and Clinic; Virginia MasonClinic; Milwaukee County Medical Complex; Mercy General Hospital;Medical College of Wisconsin; Genesee Hospital; UCLA; IndianaUniversity Medical Center; Stanford University Medical Center;Wayne State University; Johns Hopkins Oncology Center; EmoryClinic; Georgetown University Hospital; Memorial Sloan-KetteringCancer Center; University Hospital, Leiden; Cleveland ClinicFoundation; Hahnemann University Hospital; Kaiser Health CenterEast; All Children's Hospital; Dartmouth-Hitchcock Medical Center;Baylor University Medical Center; Shands Hospital, Universityof Florida; University of California, San Diego, Medical Center;University of Wisconsin; Kansas City Internal Medicine; OhioState University; New England Medical Center; Montefiore Hospital;University of Nebraska Medical Center; City of Hope NationalMedical Center; Pacific Presbyterian Hospital; University ofConnecticut John Dempsey Hospital; Children's Hospital MedicalCenter; University of California Medical Center; Universityof Kentucky Medical Center; Hotel Dieu Hospital, Louisiana StateUniversity Medical Center; Oklahoma Memorial Hospital; LawrenceMemorial Hospital; George Washington University Hospital; Dana-FarberCancer Institute; North Carolina Baptist Hospital; and Universityof Colorado Health Sciences Center.
Tsao, G. J., Allen, J. A., Logronio, K. A., Lazzeroni, L. C., Shizuru, J. A.
(2009). Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow. Proc. Natl. Acad. Sci. USA
106: 3288-3293
[Abstract][Full Text]
Schetelig, J., Bornhauser, M., Schmid, C., Hertenstein, B., Schwerdtfeger, R., Martin, H., Stelljes, M., Hegenbart, U., Schafer-Eckart, K., Fussel, M., Wiedemann, B., Thiede, C., Kienast, J., Baurmann, H., Ganser, A., Kolb, H. J., Ehninger, G.
(2008). Matched Unrelated or Matched Sibling Donors Result in Comparable Survival After Allogeneic Stem-Cell Transplantation in Elderly Patients With Acute Myeloid Leukemia: A Report From the Cooperative German Transplant Study Group. JCO
26: 5183-5191
[Abstract][Full Text]
Fausel, C.
(2007). Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm
64: S9-S15
[Abstract][Full Text]
Kawase, T., Morishima, Y., Matsuo, K., Kashiwase, K., Inoko, H., Saji, H., Kato, S., Juji, T., Kodera, Y., Sasazuki, T., for The Japan Marrow Donor Program,
(2007). High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism. Blood
110: 2235-2241
[Abstract][Full Text]
Wagner, J. E., Eapen, M., MacMillan, M. L., Harris, R. E., Pasquini, R., Boulad, F., Zhang, M.-J., Auerbach, A. D.
(2007). Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia. Blood
109: 2256-2262
[Abstract][Full Text]
Brunstein, C. G., Weisdorf, D. J., DeFor, T., Barker, J. N., Tolar, J., van Burik, J.-A. H., Wagner, J. E.
(2006). Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood
108: 2874-2880
[Abstract][Full Text]
Deeg, H. J., O'Donnell, M., Tolar, J., Agarwal, R., Harris, R. E., Feig, S. A., Territo, M. C., Collins, R. H., McSweeney, P. A., Copelan, E. A., Khan, S. P., Woolfrey, A., Storer, B.
(2006). Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood
108: 1485-1491
[Abstract][Full Text]
Chao, N. J.
(2006). Umbilical Cord Blood: Biology and Transplantation. aacredbook
2006: 329-333
[Full Text]
Pavletic, S. Z., Carter, S. L., Kernan, N. A., Henslee-Downey, J., Mendizabal, A. M., Papadopoulos, E., Gingrich, R., Casper, J., Yanovich, S., Weisdorf, D., for the members of the National Heart, Lung, and B,
(2005). Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation. Blood
106: 3308-3313
[Abstract][Full Text]
van Besien, K., Artz, A., Smith, S., Cao, D., Rich, S., Godley, L., Jones, D., Del Cerro, P., Bennett, D., Casey, B., Odenike, O., Thirman, M., Daugherty, C., Wickrema, A., Zimmerman, T., Larson, R.A., Stock, W.
(2005). Fludarabine, Melphalan, and Alemtuzumab Conditioning in Adults With Standard-Risk Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome. JCO
23: 5728-5738
[Abstract][Full Text]
Pavletic, S. Z., Khouri, I. F., Haagenson, M., King, R. J., Bierman, P. J., Bishop, M. R., Carston, M., Giralt, S., Molina, A., Copelan, E. A., Ringden, O., Roy, V., Ballen, K., Adkins, D. R., McCarthy, P., Weisdorf, D., Montserrat, E., Anasetti, C.
(2005). Unrelated Donor Marrow Transplantation for B-Cell Chronic Lymphocytic Leukemia After Using Myeloablative Conditioning: Results From the Center for International Blood and Marrow Transplant Research. JCO
23: 5788-5794
[Abstract][Full Text]
Bornstein, R., Flores, A. I., Montalban, M. A., del Rey, M. J., de la Serna, J., Gilsanz, F.
(2005). A Modified Cord Blood Collection Method Achieves Sufficient Cell Levels for Transplantation in Most Adult Patients. Stem Cells
23: 324-334
[Abstract][Full Text]
Remberger, M., Beelen, D. W., Fauser, A., Basara, N., Basu, O., Ringden, O.
(2005). Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors. Blood
105: 548-551
[Abstract][Full Text]
Takahashi, S., Iseki, T., Ooi, J., Tomonari, A., Takasugi, K., Shimohakamada, Y., Yamada, T., Uchimaru, K., Tojo, A., Shirafuji, N., Kodo, H., Tani, K., Takahashi, T., Yamaguchi, T., Asano, S.
(2004). Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood
104: 3813-3820
[Abstract][Full Text]
Laughlin, M. J., Eapen, M., Rubinstein, P., Wagner, J. E., Zhang, M.-J., Champlin, R. E., Stevens, C., Barker, J. N., Gale, R. P., Lazarus, H. M., Marks, D. I., van Rood, J. J., Scaradavou, A., Horowitz, M. M.
(2004). Outcomes after Transplantation of Cord Blood or Bone Marrow from Unrelated Donors in Adults with Leukemia. NEJM
351: 2265-2275
[Abstract][Full Text]
Petersdorf, E. W., Anasetti, C., Martin, P. J., Gooley, T., Radich, J., Malkki, M., Woolfrey, A., Smith, A., Mickelson, E., Hansen, J. A.
(2004). Limits of HLA mismatching in unrelated hematopoietic cell transplantation. Blood
104: 2976-2980
[Abstract][Full Text]
Flomenberg, N., Baxter-Lowe, L. A., Confer, D., Fernandez-Vina, M., Filipovich, A., Horowitz, M., Hurley, C., Kollman, C., Anasetti, C., Noreen, H., Begovich, A., Hildebrand, W., Petersdorf, E., Schmeckpeper, B., Setterholm, M., Trachtenberg, E., Williams, T., Yunis, E., Weisdorf, D.
(2004). Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood
104: 1923-1930
[Abstract][Full Text]
Peters, C., Charnas, L. R., Tan, Y., Ziegler, R. S., Shapiro, E. G., DeFor, T., Grewal, S. S., Orchard, P. J., Abel, S. L., Goldman, A. I., Ramsay, N. K. C., Dusenbery, K. E., Loes, D. J., Lockman, L. A., Kato, S., Aubourg, P. R., Moser, H. W., Krivit, W.
(2004). Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood
104: 881-888
[Abstract][Full Text]
Zino, E., Frumento, G., Marktel, S., Sormani, M. P., Ficara, F., Terlizzi, S. D., Parodi, A. M., Sergeant, R., Martinetti, M., Bontadini, A., Bonifazi, F., Lisini, D., Mazzi, B., Rossini, S., Servida, P., Ciceri, F., Bonini, C., Lanino, E., Bandini, G., Locatelli, F., Apperley, J., Bacigalupo, A., Ferrara, G. B., Bordignon, C., Fleischhauer, K.
(2004). A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation. Blood
103: 1417-1424
[Abstract][Full Text]
Chao, N. J., Emerson, S. G., Weinberg, K. I.
(2004). Stem Cell Transplantation (Cord Blood Transplants). ASH Education Book
2004: 354-371
[Abstract][Full Text]
Wong, R., Giralt, S. A., Martin, T., Couriel, D. R., Anagnostopoulos, A., Hosing, C., Andersson, B. S., Cano, P., Shahjahan, M., Ippoliti, C., Estey, E. H., McMannis, J., Gajewski, J. L., Champlin, R. E., de Lima, M.
(2003). Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood
102: 3052-3059
[Abstract][Full Text]
Grewal, S. S., Barker, J. N., Davies, S. M., Wagner, J. E.
(2003). Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood?. Blood
101: 4233-4244
[Full Text]
Niederwieser, D., Maris, M., Shizuru, J. A., Petersdorf, E., Hegenbart, U., Sandmaier, B. M., Maloney, D. G., Storer, B., Lange, T., Chauncey, T., Deininger, M., Ponisch, W., Anasetti, C., Woolfrey, A., Little, M.-T., Blume, K. G., McSweeney, P. A., Storb, R. F.
(2003). Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood
101: 1620-1629
[Abstract][Full Text]
Lang, P., Handgretinger, R., Niethammer, D., Schlegel, P. G., Schumm, M., Greil, J., Bader, P., Engel, C., Scheel-Walter, H., Eyrich, M., Klingebiel, T.
(2003). Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood
101: 1630-1636
[Abstract][Full Text]
Lee, S. J., Zahrieh, D., Alyea, E. P., Weller, E., Ho, V. T., Antin, J. H., Soiffer, R. J.
(2002). Comparison of T-cell-depleted and non-T-cell-depleted unrelated donor transplantation for hematologic diseases: clinical outcomes, quality of life, and costs. Blood
100: 2697-2702
[Abstract][Full Text]
Tabbara, I. A., Zimmerman, K., Morgan, C., Nahleh, Z.
(2002). Allogeneic Hematopoietic Stem Cell Transplantation: Complications and Results. Arch Intern Med
162: 1558-1566
[Abstract][Full Text]
Kojima, S., Matsuyama, T., Kato, S., Kigasawa, H., Kobayashi, R., Kikuta, A., Sakamaki, H., Ikuta, K., Tsuchida, M., Hoshi, Y., Morishima, Y., Kodera, Y.
(2002). Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood
100: 799-803
[Abstract][Full Text]
Ballen, K. K., Becker, P. S., Emmons, R. V. B., Fitzgerald, T. J., Hsieh, C. C., Liu, Q., Heyes, C., Clark, Y., Levy, W., Lambert, J. F., Chiafari, F., Szymanski, I., Rososhansky, S., Popovsky, M. A., Stewart, F. M., Quesenberry, P. J.
(2002). Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood
100: 442-450
[Abstract][Full Text]
La Nasa, G., Giardini, C., Argiolu, F., Locatelli, F., Arras, M., De Stefano, P., Ledda, A., Pizzati, A., Sanna, M. A., Vacca, A., Lucarelli, G., Contu, L.
(2002). Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes. Blood
99: 4350-4356
[Abstract][Full Text]
Silverman, L. R., Demakos, E. P., Peterson, B. L., Kornblith, A. B., Holland, J. C., Odchimar-Reissig, R., Stone, R. M., Nelson, D., Powell, B. L., DeCastro, C. M., Ellerton, J., Larson, R. A., Schiffer, C. A., Holland, J. F.
(2002). Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B. JCO
20: 2429-2440
[Abstract][Full Text]
Morishima, Y., Sasazuki, T., Inoko, H., Juji, T., Akaza, T., Yamamoto, K., Ishikawa, Y., Kato, S., Sao, H., Sakamaki, H., Kawa, K., Hamajima, N., Asano, S., Kodera, Y.
(2002). The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood
99: 4200-4206
[Abstract][Full Text]
Bunin, N., Carston, M., Wall, D., Adams, R., Casper, J., Kamani, N., King, R., the National Marrow Donor Program Working Group,
(2002). Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood
99: 3151-3157
[Abstract][Full Text]
Young, N. S.
(2002). Acquired Aplastic Anemia. ANN INTERN MED
136: 534-546
[Abstract][Full Text]
Castro-Malaspina, H., Harris, R. E., Gajewski, J., Ramsay, N., Collins, R., Dharan, B., King, R., Deeg, H. J.
(2002). Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood
99: 1943-1951
[Abstract][Full Text]
Kushida, T., Inaba, M., Ikebukuro, K., Ichioka, N., Esumi, T., Oyaizu, H., Yoshimura, T., Nagahama, T., Nakamura, K., Ito, T., Hisha, H., Sugiura, K., Yasumizu, R., Iida, H., Ikehara, S.
(2002). Comparison of Bone Marrow Cells Harvested from Various Bones of Cynomolgus Monkeys at Various Ages by Perfusion or Aspiration Methods: A Preclinical Study for Human BMT. Stem Cells
20: 155-162
[Abstract][Full Text]
Elmaagacli, A. H., Basoglu, S., Peceny, R., Trenschel, R., Ottinger, H., Lollert, A., Runde, V., Grosse-Wilde, H., Beelen, D. W., Schaefer, U. W.
(2002). Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia. Blood
99: 1130-1135
[Abstract][Full Text]
Tzachanis, D., Berezovskaya, A., Nadler, L. M., Boussiotis, V. A.
(2002). Blockade of B7/CD28 in mixed lymphocyte reaction cultures results in the generation of alternatively activated macrophages, which suppress T-cell responses. Blood
99: 1465-1473
[Abstract][Full Text]
Drobyski, W. R., Klein, J., Flomenberg, N., Pietryga, D., Vesole, D. H., Margolis, D. A., Keever-Taylor, C. A.
(2002). Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen- disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts. Blood
99: 806-814
[Abstract][Full Text]
Ho, V. T., Soiffer, R. J.
(2001). The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood
98: 3192-3204
[Full Text]
Petersdorf, E. W., Kollman, C., Hurley, C. K., Dupont, B., Nademanee, A., Begovich, A. B., Weisdorf, D., McGlave, P.
(2001). Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience. Blood
98: 2922-2929
[Abstract][Full Text]
Ferrara, G. B., Bacigalupo, A., Lamparelli, T., Lanino, E., Delfino, L., Morabito, A., Parodi, A. M., Pera, C., Pozzi, S., Sormani, M. P., Bruzzi, P., Bordo, D., Bolognesi, M., Bandini, G., Bontadini, A., Barbanti, M., Frumento, G.
(2001). Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain. Blood
98: 3150-3155
[Abstract][Full Text]
Kollman, C., Howe, C. W. S., Anasetti, C., Antin, J. H., Davies, S. M., Filipovich, A. H., Hegland, J., Kamani, N., Kernan, N. A., King, R., Ratanatharathorn, V., Weisdorf, D., Confer, D. L.
(2001). Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood
98: 2043-2051
[Abstract][Full Text]
Alpdogan, O., Schmaltz, C., Muriglan, S. J., Kappel, B. J., Perales, M.-A., Rotolo, J. A., Halm, J. A., Rich, B. E., van den Brink, M. R. M.
(2001). Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease. Blood
98: 2256-2265
[Abstract][Full Text]
Remberger, M., Ringden, O., Blau, I.-W., Ottinger, H., Kremens, B., Kiehl, M. G., Aschan, J., Beelen, D. W., Basara, N., Kumlien, G., Fauser, A. A., Runde, V.
(2001). No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors. Blood
98: 1739-1745
[Abstract][Full Text]
Williams, T. M.
(2001). Human Leukocyte Antigen Gene Polymorphism and the Histocompatibility Laboratory. J. Mol. Diagn.
3: 98-104
[Abstract][Full Text]
Laughlin, M. J., Barker, J., Bambach, B., Koc, O. N., Rizzieri, D. A., Wagner, J. E., Gerson, S. L., Lazarus, H. M., Cairo, M., Stevens, C. E., Rubinstein, P., Kurtzberg, J.
(2001). Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical-Cord Blood from Unrelated Donors. NEJM
344: 1815-1822
[Abstract][Full Text]
Cornelissen, J. J., Carston, M., Kollman, C., King, R., Dekker, A. W., Lowenberg, B., Anasetti, C.
(2001). Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood
97: 1572-1577
[Abstract][Full Text]
Soiffer, R. J., Weller, E., Alyea, E. P., Mauch, P., Webb, I. L., Fisher, D. C., Freedman, A. S., Schlossman, R. L., Gribben, J., Lee, S., Anderson, K. C., Marcus, K., Stone, R. M., Antin, J. H., Ritz, J.
(2001). CD6+ Donor Marrow T-Cell Depletion as the Sole Form of Graft-Versus-Host Disease Prophylaxis in Patients Undergoing Allogeneic Bone Marrow Transplant From Unrelated Donors. JCO
19: 1152-1159
[Abstract][Full Text]
Davies, S. M., Kollman, C., Anasetti, C., Antin, J. H., Gajewski, J., Casper, J. T., Nademanee, A., Noreen, H., King, R., Confer, D., Kernan, N. A.
(2000). Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the National Marrow Donor Program. Blood
96: 4096-4102
[Abstract][Full Text]
Kushida, T., Inaba, M., Ikebukuro, K., Ngahama, T., Oyaizu, H., Lee, S., Ito, T., Ichioka, N., Hisha, H., Sugiura, K., Miyashima, S., Ageyama, N., Ono, F., Iida, H., Ogawa, R., Ikehara, S.
(2000). A New Method for Bone Marrow Cell Harvesting. Stem Cells
18: 453-456
[Abstract][Full Text]
Kojima, S., Hibi, S., Kosaka, Y., Yamamoto, M., Tsuchida, M., Mugishima, H., Sugita, K., Yabe, H., Ohara, A., Tsukimoto, I.
(2000). Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood
96: 2049-2054
[Abstract][Full Text]
Nash, R. A., Antin, J. H., Karanes, C., Fay, J. W., Avalos, B. R., Yeager, A. M., Przepiorka, D., Davies, S., Petersen, F. B., Bartels, P., Buell, D., Fitzsimmons, W., Anasetti, C., Storb, R., Ratanatharathorn, V.
(2000). Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood
96: 2062-2068
[Abstract][Full Text]
Roux, E., Dumont-Girard, F., Starobinski, M., Siegrist, C.-A., Helg, C., Chapuis, B., Roosnek, E.
(2000). Recovery of immune reactivity after T-cell-depleted bone marrow transplantation depends on thymic activity. Blood
96: 2299-2303
[Abstract][Full Text]
Champlin, R. E., Passweg, J. R., Zhang, M.-J., Rowlings, P. A., Pelz, C. J., Atkinson, K. A., Barrett, A. J., Cahn, J.-Y., Drobyski, W. R., Gale, R. P., Goldman, J. M., Gratwohl, A., Gordon-Smith, E. C., Henslee-Downey, P. J., Herzig, R. H., Klein, J. P., Marmont, A. M., O'Reilly, R. J., Ringden, O., Slavin, S., Sobocinski, K. A., Speck, B., Weiner, R. S., Horowitz, M. M.
(2000). T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities. Blood
95: 3996-4003
[Abstract][Full Text]
Godder, K. T., Hazlett, L. J., Abhyankar, S. H., Chiang, K. Y., Christiansen, N. P., Bridges, K. D., Lee, C. G., Geier, S. S., Goon-Johnson, K. S., Gee, A. P., Pati, A. R., Parrish, R. S., Henslee-Downey, P. J.
(2000). Partially Mismatched Related-Donor Bone Marrow Transplantation for Pediatric Patients With Acute Leukemia: Younger Donors and Absence of Peripheral Blasts Improve Outcome. JCO
18: 1856-1866
[Abstract][Full Text]
McGlave, P. B., Shu, X. O., Wen, W., Anasetti, C., Nademanee, A., Champlin, R., Antin, J. H., Kernan, N. A., King, R., Weisdorf, D. J.
(2000). Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the National Marrow Donor Program. Blood
95: 2219-2225
[Abstract][Full Text]
Bacigalupo, A., Bruno, B., Saracco, P., Di Bona, E., Locasciulli, A., Locatelli, F., Gabbas, A., Dufour, C., Arcese, W., Testi, G., Broccia, G., Carotenuto, M., Coser, P., Barbui, T., Leoni, P., Ferster, A.
(2000). Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. Blood
95: 1931-1934
[Abstract][Full Text]
Vogel, W., Scheding, S., Kanz, L., Brugger, W.
(2000). Clinical Applications of CD34+ Peripheral Blood Progenitor Cells (PBPC). Stem Cells
18: 87-92
[Abstract][Full Text]
Lee, S. J., Klar, N., Weeks, J. C., Antin, J. H.
(2000). Predicting Costs of Stem-Cell Transplantation. JCO
18: 64-64
[Abstract][Full Text]
de Brabander, C, Cornelissen, J, Smitt, P A E S., Vecht, C. J, van den Bent, M J
(2000). Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors. J. Neurol. Neurosurg. Psychiatry
68: 36-40
[Abstract][Full Text]
Lowdell, M. W, Koh, M. B C
(2000). Immunotherapy of AML: future directions. J. Clin. Pathol.
53: 49-54
[Full Text]
Young, N. S., Abkowitz, J. L., Luzzatto, L.
(2000). New Insights into the Pathophysiology of Acquired Cytopenias. ASH Education Book
2000: 18-38
[Abstract][Full Text]
Green, A., Clarke, E., Hunt, L., Canterbury, A., Lankester, A., Hale, G., Waldmann, H., Goodman, S., Cornish, J. M., Marks, D. I., Steward, C. G., Oakhill, A., Pamphilon, D. H.
(1999). Children With Acute Lymphoblastic Leukemia Who Receive T-Cell-Depleted HLA Mismatched Marrow Allografts From Unrelated Donors Have an Increased Incidence of Primary Graft Failure but a Similar Overall Transplant Outcome. Blood
94: 2236-2246
[Abstract][Full Text]
Lowenberg, B., Downing, J. R., Burnett, A.
(1999). Acute Myeloid Leukemia. NEJM
341: 1051-1062
[Full Text]
Young, N. S.
(1999). Acquired Aplastic Anemia. JAMA
282: 271-278
[Full Text]
Socie, G., Stone, J. V., Wingard, J. R., Weisdorf, D., Henslee-Downey, P. J., Bredeson, C., Cahn, J.-Y., Passweg, J. R., Rowlings, P. A., Schouten, H. C., Kolb, H.-J., Klein, J. P., Bender-Gotze, C., Camitta, B. M., Godder, K., Horowitz, M. M., Wayne, A. S., The Late Effects Working Committee of the Internat,
(1999). Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation. NEJM
341: 14-21
[Abstract][Full Text]
Locatelli, F., Rocha, V., Chastang, C., Arcese, W., Michel, G., Abecasis, M., Messina, C., Ortega, J., Badell-Serra, I., Plouvier, E., Souillet, G., Jouet, J.-P., Pasquini, R., Ferreira, E., Garnier, F., Gluckman, E.
(1999). Factors Associated With Outcome After Cord Blood Transplantation in Children With Acute Leukemia. Blood
93: 3662-3671
[Abstract][Full Text]
Small, T.N., Papadopoulos, E.B., Boulad, F., Black, P., Castro-Malaspina, H., Childs, B.H., Collins, N., Gillio, A., George, D., Jakubowski, A., Heller, G., Fazzari, M., Kernan, N., MacKinnon, S., Szabolcs, P., Young, J.W., O'Reilly, R.J.
(1999). Comparison of Immune Reconstitution After Unrelated and Related T-Cell-Depleted Bone Marrow Transplantation: Effect of Patient Age and Donor Leukocyte Infusions. Blood
93: 467-480
[Abstract][Full Text]
Prasad, V. K., Kernan, N. A., Heller, G., O'Reilly, R. J., Yang, S. Y.
(1999). DNA Typing for HLA-A and HLA-B Identifies Disparities Between Patients and Unrelated Donors Matched by HLA-A and HLA-B Serology and HLA-DRB1. Blood
93: 399-409
[Abstract][Full Text]
Dumont-Girard, F., Roux, E., van Lier, R. A., Hale, G., Helg, C., Chapuis, B., Starobinski, M., Roosnek, E.
(1998). Reconstitution of the T-Cell Compartment After Bone Marrow Transplantation: Restoration of the Repertoire by Thymic Emigrants. Blood
92: 4464-4471
[Abstract][Full Text]
Rubinstein, P., Carrier, C., Scaradavou, A., Kurtzberg, J., Adamson, J., Migliaccio, A. R., Berkowitz, R. L., Cabbad, M., Dobrila, N. L., Taylor, P. E., Rosenfield, R. E., Stevens, C. E.
(1998). Outcomes among 562 Recipients of Placental-Blood Transplants from Unrelated Donors. NEJM
339: 1565-1577
[Abstract][Full Text]
Petersdorf, E. W., Gooley, T. A., Anasetti, C., Martin, P. J., Smith, A. G., Mickelson, E. M., Woolfrey, A. E., Hansen, J. A.
(1998). Optimizing Outcome After Unrelated Marrow Transplantation by Comprehensive Matching of HLA Class I and II Alleles in the Donor and Recipient. Blood
92: 3515-3520
[Abstract][Full Text]
Kawano, Y., Takaue, Y., Watanabe, A., Takeda, O., Arai, K., Itoh, E., Ohno, Y., Teshima, T., Harada, M., Watanabe, T., Okamoto, Y., Abe, T., Kajiume, T., Matsushita, T., Ikeda, K., Endo, M., Kuroda, Y., Asano, S., Tanosaki, R., Yamaguchi, K., Law, P., McMannis, J. D.
(1998). Partially Mismatched Pediatric Transplants With Allogeneic CD34+ Blood Cells From a Related Donor. Blood
92: 3123-3130
[Abstract][Full Text]
Sasazuki, T., Juji, T., Morishima, Y., Kinukawa, N., Kashiwabara, H., Inoko, H., Yoshida, T., Kimura, A., Akaza, T., Kamikawaji, N., Kodera, Y., Takaku, F., Nose, Y., Ono, T., Sakamaki, T., Kato, S., Akiyama, Y., Okamoto, S., Dohy, H., Harada, M., Asano, S., The Japan Marrow Donor Program,
(1998). Effect of Matching of Class I HLA Alleles on Clinical Outcome after Transplantation of Hematopoietic Stem Cells from an Unrelated Donor. NEJM
339: 1177-1185
[Abstract][Full Text]
Aversa, F., Tabilio, A., Velardi, A., Cunningham, I., Terenzi, A., Falzetti, F., Ruggeri, L., Barbabietola, G., Aristei, C., Latini, P., Reisner, Y., Martelli, M. F., Felicini, R., Falcinelli, F., Carotti, A., Perruccio, K., Ballanti, S., Santucci, A., Gambelunghe, C.
(1998). Treatment of High-Risk Acute Leukemia with T-Cell-Depleted Stem Cells from Related Donors with One Fully Mismatched HLA Haplotype. NEJM
339: 1186-1193
[Abstract][Full Text]
Drobyski, W. R., Majewski, D., Ozker, K., Hanson, G.
(1998). Ex Vivo Anti-CD3 Antibody-Activated Donor T Cells Have a Reduced Ability to Cause Lethal Murine Graft-Versus-Host Disease but Retain Their Ability to Facilitate Alloengraftment. J. Immunol.
161: 2610-2619
[Abstract][Full Text]
Bernstein, S. H., Nademanee, A. P., Vose, J. M., Tricot, G., Fay, J. W., Negrin, R. S., DiPersio, J., Rondon, G., Champlin, R., Barnett, M. J., Cornetta, K., Herzig, G. P., Vaughan, W., Geils, G. Jr, Keating, A., Messner, H., Wolff, S. N., Miller, K. B., Linker, C., Cairo, M., Hellmann, S., Ashby, M., Stryker, S., Nash, R. A.
(1998). A Multicenter Study of Platelet Recovery and Utilization in Patients After Myeloablative Therapy and Hematopoietic Stem Cell Transplantation. Blood
91: 3509-3517
[Abstract][Full Text]
Deeg, H. J., Socie, G.
(1998). Malignancies After Hematopoietic Stem Cell Transplantation: Many Questions, Some Answers. Blood
91: 1833-1844
[Full Text]
Cairo, M. S., Wagner, J. E.
(1997). Placental and/or Umbilical Cord Blood: An Alternative Source of Hematopoietic Stem Cells for Transplantation. Blood
90: 4665-4678
[Full Text]
Weisdorf, D. J., Billett, A. L., Hannan, P., Ritz, J., Sallan, S. E., Steinbuch, M., Ramsay, N. K.C.
(1997). Autologous Versus Unrelated Donor Allogeneic Marrow Transplantation for Acute Lymphoblastic Leukemia. Blood
90: 2962-2968
[Abstract][Full Text]
Sierra, J., Storer, B., Hansen, J. A., Bjerke, J. W., Martin, P. J., Petersdorf, E. W., Appelbaum, F. R., Bryant, E., Chauncey, T. R., Sale, G., Sanders, J. E., Storb, R., Sullivan, K. M., Anasetti, C.
(1997). Transplantation of Marrow Cells From Unrelated Donors for Treatment of High-Risk Acute Leukemia: The Effect of Leukemic Burden, Donor HLA-Matching, and Marrow Cell Dose. Blood
89: 4226-4235
[Abstract][Full Text]
Henslee-Downey, P. J., Abhyankar, S. H., Parrish, R. S., Pati, A. R., Godder, K. T., Neglia, W. J., Goon-Johnson, K. S., Geier, S. S., Lee, C. G., Gee, A. P.
(1997). Use of Partially Mismatched Related Donors Extends Access to Allogeneic Marrow Transplant. Blood
89: 3864-3872
[Abstract][Full Text]
Brown, K. E., Tisdale, J., Barrett, A. J., Dunbar, C. E., Young, N. S.
(1997). Hepatitis-Associated Aplastic Anemia. NEJM
336: 1059-1064
[Abstract][Full Text]
Rottman, G. A., Ramirez, M., Civin, C. I.
(1997). Cord Blood Transplantation: A Promising Future. Pediatrics
99: 475-475
[Full Text]
Petersdorf, E. W., Longton, G. M., Anasetti, C., Mickelson, E. M., McKinney, S. K., Smith, A. G., Martin, P. J., Hansen, J. A.
(1997). Association of HLA-C Disparity With Graft Failure After Marrow Transplantation From Unrelated Donors. Blood
89: 1818-1823
[Abstract][Full Text]
Hauptman, P. J., O'Connor, K. J.
(1997). Procurement and Allocation of Solid Organs for Transplantation. NEJM
336: 422-431
[Full Text]
Cheson, B. D.
(1997). The Myelodysplastic Syndromes. The Oncologist
2: 28-39
[Abstract][Full Text]
Haddad, E., Sulis, M.-L., Jabado, N., Blanche, S., Fischer, A., Tardieu, M.
(1997). Frequency and Severity of Central Nervous System Lesions in Hemophagocytic Lymphohistiocytosis. Blood
89: 794-800
[Abstract][Full Text]
Forte, K. J.
(1997). Alternative Donor Sources in Pediatric Bone Marrow Transplantation. Journal of Pediatric Oncology Nursing
14: 213-224
[Abstract]
Petersdorf, E. W., Longton, G. M., Anasetti, C., Mickelson, E. M., Smith, A. G., Martin, P. J., Hansen, J. A.
(1996). Definition of HLA-DQ as a transplantation antigen. Proc. Natl. Acad. Sci. USA
93: 15358-15363
[Abstract][Full Text]
Kurtzberg, J., Laughlin, M., Graham, M. L., Smith, C., Olson, J. F., Halperin, E. C., Ciocci, G., Carrier, C., Stevens, C. E., Rubinstein, P.
(1996). Placental Blood as a Source of Hematopoietic Stem Cells for Transplantation into Unrelated Recipients. NEJM
335: 157-166
[Abstract][Full Text]
Pavletic, Z. S., Armitage, J. O.
(1996). Bone Marrow Transplantation for Cancer--An Update. The Oncologist
1: 159-168
[Abstract][Full Text]
Kernan, N. A., Dupont, B.
(1996). Minor Histocompatibility Antigens and Marrow Transplantation. NEJM
334: 323-324
[Full Text]
Silberman, G., Crosse, M. G., Peterson, E. A., Weston, R. C., Horowitz, M. M., Appelbaum, F. R., Cheson, B. D.
(1994). Availability and Appropriateness of Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia in 10 Countries. NEJM
331: 1063-1067
[Abstract][Full Text]
Verhoef, L. C.G., De Haan, A. F.J., Van Daal, W. A.J.
(1994). Risk Attitude in Gambles with Years of Life: Empirical Support for Prospect Theory. Med Decis Making
14: 194-200
[Abstract]
Scornik, J. C., Kernan, N. A., Hansen, J. A., Blume, K. G.
(1993). Marrow Transplants from Unrelated Donors. NEJM
329: 362-363
[Full Text]