The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT … (original) (raw)
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Leukemia, 2010
We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P ¼ 0.82. In contrast, OS was significantly worse for MM (37% (29-48) P ¼ 0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P ¼ 0.11 and MM: 21% (18-24), P ¼ 0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.
Bone Marrow Transplantation, 2020
Patients with acute myeloid leukaemia (AML) who lack a matched sibling or unrelated donor commonly undergo transplantation from a donor matched at 9/10 HLA-A,-B,-C,-DRB1,-DQB1 alleles, and it is unclear if a specific locus mismatch is preferable to any other. We therefore studied 937 patients with AML in complete remission transplanted using a reduced intensity conditioning regimen from an unrelated donor mismatched at a single allele. In a multivariate analysis, patient age, adverse karyotype and patient cytomegalovirus (CMV) seropositivity were correlated with decreased leukaemia free survival (LFS) and overall survival (OS). There was no significant difference in LFS or OS between patients transplanted from donors mismatched at HLA-A,-B,-C or-DRB1 in comparison to a HLA-DQB1 mismatched transplant. In a multivariate analysis, patients transplanted with a HLA-A mismatched donor had higher rates of acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM) than patients transplanted with a HLA-DQB1 mismatched donor. Patient CMV seropositivity was associated with an increase in NRM and acute GVHD and reduced LFS and OS, regardless of donor CMV status. For CMV seropositive patients lacking a fully matched donor, alternative GVHD and CMV prophylaxis strategies should be considered.
Isolated HLA-C mismatches in unrelated donor transplantation for CML
Bone Marrow Transplantation, 2004
HLA-incompatibility is a major factor associated with outcome of allogeneic stem cell transplantation, but little is known on the impact of isolated HLA-C mismatches. We analyzed the outcome of 114 CML patients transplanted with marrow from unrelated donors of whom 24 were mismatched for HLA-C only (9/10 match). Univariate estimates of 5-year survival (SRV) (median follow-up: 47 months) in the HLA-matched group were 68712 vs 42720% (P ¼ 0.03) for the patients mismatched for HLA-C only and 33733% in the mismatched group (non-HLA-C single mismatches and multiple mismatches) (P ¼ 0.0004). Disease stage, GVHD-prophylaxis (T-cell depletion), CMV-status and HLA-incompatibility were the risk factors associated (all Pp0.005) with poor outcome. In the multivariate analysis, patients mismatched for loci other than HLA-C were at high risk of an adverse outcome (death:
Bone Marrow Transplantation, 1997
Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-(P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients trans-chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year planted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females LFS, TRM and relapse incidence for this group were 51 ± 5%, 47 ± 5% and 2 ± 2%, respectively. This sug-was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median gests that the long-term outcome of patients with favorable prognostic features can approach that of patients interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. justifiable for these individuals. Keywords: chronic myeloid leukemia; unrelated donor Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compati-bone marrow transplant bility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirtyone patients received BMT from a donor who was HLA-For patients with CML, allogeneic BMT from an HLA-DRB1 mismatched (group 2) and 59 from a donor in identical sibling is the treatment of choice. 1-4 However, whom specific HLA-DRB1 typing was not performed most patients do not have a suitable sibling donor and, for (group 3). The overall survival was 37 ± 3% at 2 years these individuals, there are a number of treatment options. and leukemia-free survival (LFS) was 31 ± 3%. In univ-
Blood, 2010
We compared the outcomes of unrelated donor (URD, n = 358) with human leukocyte antigen (HLA)–matched sibling donor (MSD, n = 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (≥ 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6;9), 5%; and other noncomplex, 10%. URDs were HLA-well-matched (n = 254; 71%) or partially-matched (n = 104; 29%). Three-year leukemia-free survival (LFS) for MSD was 42% (95% confidence interval [CI], 35%-48%) compared with 34% (95% CI, 28%-41%) for HLA-well-matched URD and 29% (95% CI, 20%-39%) for partially-matched URD (P = .08). In multivariate analysis, HLA-well-matched URD and MSD yielded similar LFS (relative risk [RR] = 1.1, 95% CI, 0.86-1.40, P = .44) and overall survival (OS; RR = 1.06, 95% CI, 0.83-1.37, P = .63). LFS and OS were s...
Biology of Blood and Marrow Transplantation, 2015
Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n ¼ 2025) or single-locus mismatched (n ¼ 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1-and 3-year OS was better in 8/8-versus 7/8-matched recipients (54.7% versus 48.8%, P ¼ .01, and 37.4% versus 30.9%, P ¼ .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR ¼ 1.29, P ¼ .0034), higher TRM (RR ¼ 1.52, P < .0001), and lower DFS (RR ¼ 1.12, P ¼ .0015) and OS (RR ¼ 1.25, P ¼ .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DP1 (based on T celleepitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes.
Blood, 2009
Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]–matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR,...
Unrelated Donor Hematopoietic Cell Transplantation: Factors Associated with a Better HLA Match
Biology of Blood and Marrow Transplantation, 2008
We analyzed the outcomes of 283 patients receiving unrelated donor allogeneic hematopoietic cell transplantation for non-Hodgkin lymphoma (NHL) facilitated by the Center for International Blood & Marrow Transplant Research /National Marrow Donor Program (CIBMTR/NMDP) between 1991 and 2004. All patients received myeloablative conditioning regimens. The median follow-up of survivors is 5 years. Seventy-three (26%) patients are alive. The day 100 probability of death from all causes is estimated at 39%. The cumulative incidence of developing grade III-IV acute graft-versus-host disease (GVHD) at day 100 is 25%. The estimated five-year survival and failure free survival are 24% (95% CI; 19-30) and 22% (95% CI; 17-28) respectively. Factors adversely associated with overall survival included increasing age, decreased performance status, and refractory disease. Follicular lymphoma and Peripheral T-cell lymphoma had improved survival compared to aggressive B-cell lymphomas. Factors adversely associated with progression free-survival included performance status, histology and disease status at transplant. Long-term failure-free survival is possible following unrelated donor transplantation for NHL, although early mortality was high in this large cohort.