scholarly journals HLA Class II Epitope Mismatch Influences Relapse and Engraftment in Peripheral Blood Haploidentical Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4634-4634
Author(s):  
Joseph Rimando ◽  
Michael Slade ◽  
Feng Gao ◽  
Rizwan Romee ◽  
Chang Liu
Keyword(s):  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Class Ii ◽  
Hematopoietic Cell ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Delayed Time ◽  
Neutrophil Engraftment

Abstract Background: High dose post-transplant cyclophosphamide has improved and expanded the use of haploidentical hematopoietic cell transplantation (haplo-HCT). The impact of HLA disparity in this setting, however, is unclear and traditionally measured at the antigen or allele level. The HLA Matchmaker tool more precisely quantifies HLA disparity by calculating the number of mismatched three-dimensional amino acid patches, or epitopes, on the surface of two mismatched HLA antigens. Previous research has shown that class II epitope mismatch (EM), which includes the combination of DRB1 and DQB1 EM, is associated with reduced relapse and delayed engraftment in haplo-HCT (Rimando et al, ASBMT 2018 Abstract ID#53). The individual impact of DRB1 and DQB1 EM on clinical outcomes is currently unclear. Methods: 148 patients who received a peripheral blood T cell-replete haplo-HCT at a single center between July 2009 and November 2017 were retrospectively analyzed. All patients age ≥ 18 were included regardless of diagnosis. The HLA EM load for total class II disparity, DRB1, and DQB1 was quantified using the HLA Matchmaker software and a python script in a dose-dependent and vector-stratified fashion. The primary outcome was the incidence of relapse. The secondary outcomes included relapse-free survival (RFS), time to neutrophil engraftment, and time to platelet engraftment. The association between HLA EM and outcome was analyzed using the Cox proportional hazard model or Gray's sub-distribution method for competing risk as appropriate. The hazard ratios calculated report the hazard rate for a single unit increase in EM. This study was approved by the Institutional Review Board. Results: In this updated cohort, class II graft-versus-host (GvH) EM was again associated with reduced incidence of relapse (HR 0.966; 95% CI 0.938-0.995; p=0.023) and improved RFS (HR 0.978; 95% CI 0.957-0.999; p=0.037) (Table 1). Class II host-versus-graft (HvG) EM was again associated with delayed neutrophil (HR 0.976; 95% CI 0.955-0.997; p=0.027) and platelet (HR 0.971; 95% CI 0.950-0.993; p=0.010) engraftment. Neither DRB1 nor DQB1 GvH EM was independently associated with relapse or RFS. DRB1 HvG EM was associated with worse relapse-free survival (HR 1.038; 95% CI 1.002-1.076; p=0.040). DRB1 HvG EM was associated with delayed time to neutrophil engraftment (HR 0.965; 95% CI 0.934-0.997; p=0.033), while DQB1 HvG EM was not. DQB1 HvG EM was associated with delayed time to platelet engraftment (HR 0.967; 95% CI 0.938-0.997; p=0.032), while DRB1 HvG EM was not. Summary: HLA Matchmaker software enables the quantification of HLA EM in haplo-HCT patients. Neither DRB1 nor DQB1 GvH EM was independently associated with relapse or RFS. DRB1 HvG EM was associated with neutrophil but not platelet engraftment, while DQB1 HvG EM was associated with platelet but not neutrophil engraftment. HLA EM represents a novel strategy to predict clinical outcome in haplo-HCT. The mechanism for the divergent roles of DRB1 EM and DQB1 EM on neutrophil and platelet engraftment are currently unknown and warrant further investigation. Disclosures No relevant conflicts of interest to declare.

scholarly journals HLA-haploidentical vs matched-sibling hematopoietic cell transplantation: a systematic review and meta-analysis

2019 ◽  
Vol 3 (17) ◽  
pp. 2581-2585 ◽  
Author(s):  
Mohamad A. Meybodi ◽  
Wenhao Cao ◽  
Leo Luznik ◽  
Asad Bashey ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Relative Contribution ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Matched Sibling ◽  
Outcome Differences

Abstract 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.

scholarly journals Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab

2020 ◽  
Vol 4 (10) ◽  
pp. 2308-2316 ◽  
Author(s):  
Talha Badar ◽  
Aniko Szabo ◽  
Anjali Advani ◽  
Martha Wadleigh ◽  
Shukaib Arslan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Complete Remission ◽  
B Cell ◽  
Cell Transplantation ◽  
Real World ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Count Recovery

Abstract The availability and use of blinatumomab symbolizes a paradigm shift in the management of B-cell acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter cohort analysis of 239 ALL patients (227 relapsed refractory [RR], n = 227; minimal residual disease [MRD], n = 12) who received blinatumomab outside of clinical trials to evaluate safety and efficacy in the “real-world” setting. The median age of patients at blinatumomab initiation was 48 years (range, 18-85). Sixty-one (26%) patients had ≥3 prior therapies and 46 (19%) had allogeneic hematopoietic cell transplantation before blinatumomab. The response rate (complete remission/complete remission with incomplete count recovery) in patients with RR disease was 65% (47% MRD−). Among 12 patients who received blinatumomab for MRD, 9 (75%) patients achieved MRD negativity. In patients with RR disease, median relapse-free survival and overall survival (OS) after blinatumomab was 32 months and 12.7 months, respectively. Among patients who received blinatumomab for MRD, median relapse-free survival was not reached (54% MRD− at 2 years) and OS was 34.7 months. Grade ≥3 cytokine release syndrome, neurotoxicity, and hepatotoxicity were observed in 3%, 7%, and 10% of patients, respectively. Among patients who achieved complete remission/complete remission with incomplete count recovery, consolidation therapy with allogeneic hematopoietic cell transplantation retained favorable prognostic significance for OS (hazard ratio, 0.54; 95% confidence interval, 0.30-0.97; P = .04). In this largest “real-world” experience published to date, blinatumomab demonstrated responses comparable to those reported in clinical trials. The optimal sequencing of newer therapies in ALL requires further study.

scholarly journals Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 726-732 ◽  
Author(s):  
Sarah Cooley ◽  
Elizabeth Trachtenberg ◽  
Tracy L. Bergemann ◽  
Koy Saeteurn ◽  
John Klein ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Killer Cell ◽  
Hematopoietic Cell ◽  
Myelogenous Leukemia ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Kir Haplotypes

Abstract Survival for patients with acute myeloid leukemia (AML) is limited by treatment-related mortality (TRM) and relapse after unrelated donor (URD) hematopoietic cell transplantation (HCT). Natural killer (NK)–cell alloreactivity, determined by donor killer-cell immunoglobulin-like receptors (KIRs) and recipient HLA, correlates with successful HCT for AML. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: at least 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 209 HLA-matched and 239 mismatched T-replete URD transplantations for AML. Three-year overall survival was significantly higher after transplantation from a KIR B/x donor (31% [95% CI: 26-36] vs 20% [95% CI: 13-27]; P = .007). Multivariate analysis demonstrated a 30% improvement in the relative risk of relapse-free survival with B/x donors compared with A/A donors (RR: 0.70 [95% CI: 0.55-0.88]; P = .002). B/x donors were associated with a higher incidence of chronic graft-versus-host disease (GVHD; RR: 1.51 [95% CI: 1.01-2.18]; P = .03), but not of acute GVHD, relapse, or TRM. This analysis demonstrates that unrelated donors with KIR B haplotypes confer significant survival benefit to patients undergoing T-replete HCT for AML. KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes.

scholarly journals Factors Predicting Gvhd Free, Relapse Free Survival (GRFS) after Allogeneic Hematopoietic Cell Transplantation; A Multivariable Analysis of 531 Allografts from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2028-2028
Author(s):  
Melhem Solh ◽  
Xu Zhang ◽  
Katelin Connor ◽  
Stacey Brown ◽  
H. Kent Holland ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
One Year ◽  
Very High

Abstract The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, GVHD and non-relapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT (1). We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grade 3-4, moderate to severe chronic GVHD, relapse or death in 531 consecutive adult patients who received an allo- HCT between 2006 and 2014 at our center. Median follow up of living patients was 46 months (12-123). Patients were treated using standardized supportive care algorithms at our center. Although this was a retrospective analysis, patient characteristics and outcomes including GVHD grading were obtained from our institutional database where they had been prospectively documented. The median age was 52 (18-77) years. 266 (50%) received myeloablative conditioning, and 428 (81%) received PBSC as stem cell source. Donor type was HLA matched related (MRD, n=198, 37%), matched unrelated (MUD, n=205, 39%) and haploidentical using T-replete grafts and post-transplant cyclophosphamide (HIDT, n=128, 24%). 36% of patients had a high/very high Dana farber disease risk index (DRI). The most common indications for transplant were AML (n=197, 37%), MDS/MPS (n=114, 21%), NHL (n=132, 25%) and ALL (n=68, 13%).1 year OS, disease free survival DFS and GRFS were 78%, 64% and 33% respectively. GRFS after MRD, MUD and HIDT was 39%, 27% and 35% respectively, with MRD recipients having a better GRFS than MUD (p=0.004). Regression analysis showed that GRFS at the one year was lower for, patients transplanted before 2011 than those transplanted between 2011 and 2014(27% vs 39%, p=0.0031), high CIBMTR disease risk than low CIBMTR risk (24% vs 39%, p=0.009) and high/very high DRI than low DRI (23% vs 48%, p<0.001). On multivariable analysis, year of transplant before 2011 (HR =1.2, p=0.03), age >= 50 years (HR 1.22, p=0.05), MUD donor (HR 1.3, p=0.004) and high/very high DRI risk (HR 2.05, p<0.001) were all associated with a worse GFRS at one year post HCT. GFRS is an endpoint that is worth investigating in further trials as a marker of successful HCT. These data suggest that GRFS can be predicted by patient age and DRI but not by HCT-CMI. Importantly the GRFS appears to have improved in more recently transplanted patients and MUD donors produce inferior GRFS to MRD whereas haploidentical donors do not. Table 1. Predictors of GRFS at one year N=531 1 year GRFS HR 95% CI P value Year of BMT2005-2010 2011-2014 270 (51%) 261 (49%) 30% 37% 1.00 0.80 25%-35% 32%-43% - 0.03 AgeAge <50 years Age >= 50 years 228 (43%) 303(57%) 37% 31% 1.00 1.22 31%-43% 26%-36% - 0.05 Donor TypeMRD MUD Haplo Haplo vs MUD 198(37%) 205 (39%) 128 (24%) 39% 27% 35% 1.00 1.30 1.13 0.81 33%-45% 22%-33% 27%-42% - 0.004 0.379 0.112 DRILow Intermediate High/very high 78(15%) 258 (49%) 189 (36%) 48% 36% 23% 1.00 1.42 2.05 38%-58% 31%-42% 18%-29% - 0.025 <0.001 1. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-8. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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