Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
Ontology highlight
ABSTRACT:
SUBMITTER: Nagler A
PROVIDER: S-EPMC8017786 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
| S-EPMC8753217 | biostudies-literature
Project description:HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.
| S-EPMC6595262 | biostudies-literature
Project description:Allogeneic blood or marrow hematopoietic cell transplantation continues to be the most potent anti-leukemic treatment for adult patients with standard, high-risk, or chemo-refractory acute myeloid leukemia. Until recently, this procedure was generally limited to those recipients who had an available matched-sibling donor or matched-unrelated donor. Technical advances in graft cell processing and manipulation, control of bidirectional T cell alloreactivity, graft-versus-host disease prophylaxis, and other supportive measures in haploidentical transplantation now enable nearly all patients with acute myeloid leukemia to benefit from the graft-versus-leukemia effect with substantial reduction in procedure-related mortality. Over recent years, haploidentical donors have been increasingly adopted as a valid donor source in allogeneic hematopoietic cell transplantation for acute myeloid leukemia in the absence of an HLA-matched donor. Among centers of the European Society for Blood and Marrow Transplantation, the use of haploidentical related donor transplantation has increased by 250% since 2010, and 291% since 2005. On behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize recent utilization trends in haploidentical transplantation for acute myeloid leukemia and describe the transformative changes in haploidentical hematopoietic cell transplantation techniques over the past decade, which have led to the current widespread use of this procedure. Furthermore, we review the efficacy of haploidentical hematopoietic cell transplantation for acute myeloid leukemia from available studies, including preliminary comparative studies, and bring attention to remaining unanswered questions and directions for future research. We conclude this report with our recommendations for the role of haploidentical hematopoietic cell transplantation in acute myeloid leukemia.
| S-EPMC5664385 | biostudies-literature
Project description:BackgroundAllogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors.MethodsWe performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014.ResultsMedian age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on anti-thymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II-IV acute-graft-versus-host-disease (GVHD) was 31%, grade III-IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS.ConclusionsUnmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status.
| S-EPMC5450162 | biostudies-literature
Project description:Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate - acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated (Haplo) to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were intermediate and high-risk acute myeloid leukemia in first complete remission undergoing Haplo and matched sibling donor transplant from 2007-2015, and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donors were matched with 1 Haplo. We identified 2654 pts (Haplo =185; matched sibling donor =2469), 2010 with intermediate acute myeloid leukemia (Haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (Haplo =63; matched sibling donor =581). Median follow up was 30 (range 1-116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, Haplo resulted in lower leukemia-free survival (Hazard Ratio 1.74; P<0.01), overall-survival (HR 1.80; P<0.01) and GvHD-free-relapse-free survival (Hazard Ratio 1.32; P<0.05) and higher graft-versus-host disease (GvHD) non-relapse mortality (Hazard Ratio 3.03; P<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free survival, overall-survival, and GvHD-free- relapse-free survival according to donor type. Higher grade II-IV acute GvHD was observed for Haplo in both high-risk (Hazard Ratio 2.20; P<0.01) and intermediate risk (Hazard Ratio 1.84; P<0.01). A trend for a lower Relapse-Incidence was observed in Haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; P=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of Haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.
| S-EPMC6068036 | biostudies-literature
Project description:Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.
| S-EPMC2981549 | biostudies-literature
Project description:PurposeRelated donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry.Materials and methodsWe evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis.ResultsMedian follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34).ConclusionHaplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.
| S-EPMC5012706 | biostudies-literature
Project description:BACKGROUND:Compared with HLA-matched sibling donor (MSD) transplant, the outcomes of haploidentical donor (HID) transplant for refractory acute leukemia need to be further explored. In this study, we compared the outcomes of HID with MSD for refractory acute leukemia. PATIENTS AND METHODS:This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Two hundred and seventy-eight patients with refractory acute leukemia were enrolled in this study, including 119 in HID group and 132 in MSD group. Sequential intensified conditioning was employed in all patients, and donor lymphocyte infusion (DLI) was administered in patients in the absence of active GVHD and according to minimal residual disease (MRD) from day + 60 post-transplantation for preventing relapse. RESULTS:The complete remission of leukemia by day + 30 post-transplant were 94% and 93%, respectively, in HID and MSD groups (p = .802). The 1-year incidence of grades II-IV acute GVHD was 62% and 54% (p = .025), and 3-year incidence of chronic GVHD was 55% and 55% (p = .789), respectively, in two groups. HID transplant had lower incidence of first episode of MRD positivity and relapse than MSD transplant (28% vs 45%, p = .006; 26% vs 38%, p = .034). There was higher infection-related mortality in HID than MSD (8% vs 2%, p = .049) within the first 100?days' post-transplant. The 5-year overall survival was 46% and 42% (p = .832), respectively; the 5-year disease-free survival was 43% and 39% (p = .665), in HID and MSD groups, respectively. CONCLUSIONS:HID transplant has lower relapse, but higher infection-related mortality and similar survival rates in refractory acute leukemia by the strategy of sequential intensified conditioning followed by DLI compared with MSD transplant.
| S-EPMC7068952 | biostudies-literature
Project description:Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia (AML) is a common high-risk feature that is referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with AML harboring -5/5q- having their first allogeneic transplantation between 2000 and 2015. Five hundred and one patients with -5/5q- have been analyzed. Three hundred and thirty-eight patients (67%) were in first remission and 142 (28%) had an active disease at time of allogeneic transplantation. The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. We identified four different cytogenetic groups according to additional abnormalities with prognostic impact: -5/5q- without complex karyotype, monosomal karyotype or abn(17p), -5/5q- within a complex karyotype, -5/5q- within a monosomal karyotype and the combination of -5/5q- with abn(17p). In multivariate analysis, factors associated with worse overall survival and leukemia-free survival across the four groups were active disease, age, monosomal karyotype, and abn(17p). The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.
| S-EPMC7012466 | biostudies-literature
Project description:HLA haploidentical hematopoietic cell transplantation (haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) is an alternative strategy when a matched sibling donor (MSD) is not available. We performed a systematic review and meta-analysis to compare the outcomes of MSD vs haplo-HCT. Eleven studies (1410 haplo-HCT and 6396 MSD recipients) were meta-analyzed. All studies were retrospective and high quality, and 9 were multicenter. Haplo-HCT was associated with ~50% lower risk of chronic graft-versus-host disease (GVHD) (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.41-0.74), but higher risk of nonrelapse mortality (HR, 1.36; 95% CI, 1.12-1.66). Relapse, survival, acute GVHD, and GVHD-free relapse-free survival were not significantly different between the groups. Deciphering the relative contribution of PT-Cy and HLA disparity to the observed outcome differences between the groups requires further research.
| S-EPMC6737418 | biostudies-literature