Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation

Yr, Ma; Xu, Lei; Xh, Zhang; Ch, Yan; Wang, Y; Fr, Wang; Jz, Wang; Chen, Y; Wang, Han; Chen, Y-H.; Chen, H; Ky, Lee; Huang, Xiao‐Jun

doi:10.1038/bmt.2016.283

Cited by 15 publications

(6 citation statements)

References 34 publications

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“…With the use of posttransplant cyclophosphamide (PTCy) to selectively deplete alloreactive T cells, [6][7][8][9][10] haplo-HCT has been shown to have similar outcomes when compared with MUD allo-HCT. 8,[11][12][13][14][15][16][17] Given the increased donor availability for haplo-HCT, several studies have investigated the impact of donor characteristics on clinical outcomes, with HLA disparity representing a topic of particular interest. [18][19][20][21][22] For patients undergoing mismatched unrelated allo-HCT, increased HLA mismatch has been associated with inferior survival and increased treatment-related mortality (TRM).…”

Section: Introductionmentioning

confidence: 99%

HLA epitope mismatch in haploidentical transplantation is associated with decreased relapse and delayed engraftment

et al. 2018

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HLA disparity is traditionally measured at the antigen or allele level, and its impact on haploidentical hematopoietic cell transplantation (haplo-HCT) with high-dose posttransplant cyclophosphamide (PTCy) is unclear. To the best of our knowledge, the relationship between HLA eplet–derived epitope mismatch (EM) and clinical outcome has not been examined in haplo-HCT. We retrospectively analyzed 148 patients who received a peripheral blood, T-cell–replete haplo-HCT with PTCy at a single center. HLA EM was quantified using an HLAMatchmaker-based method and was stratified by class and vector. The primary outcome was incidence of relapse. The total number of mismatched epitopes (MEs) per patient-donor pair in our patient population ranged from 0 to 51 (median, 24) in the graft-versus-host (GVH) direction and 0 to 47 (median, 24) in the host-versus-graft (HVG) direction. Higher HLA class II EM in the GVH direction was associated with a significantly reduced risk of relapse (adjusted hazard ratio [HR], 0.952 per ME; P = .002) and improved relapse-free survival (adjusted HR, 0.974 per ME; P = .020). Higher HLA class II EM in the HVG direction was associated with longer time to neutrophil (adjusted HR, 0.974 per ME; P = .013) and platelet (adjusted HR, 0.961 per ME; P = .001) engraftment. In peripheral blood haplo-HCT patients, increased HLA EM was associated with a protective effect on the risk of relapse in the GVH direction but a negative effect on time to count recovery in the HVG direction. HLA EM based on the HLA Matchmaker represents a novel strategy to predict clinical outcome in haplo-HCT.

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Section: Introductionmentioning

confidence: 99%

HLA epitope mismatch in haploidentical transplantation is associated with decreased relapse and delayed engraftment

et al. 2018

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“…Successful outcomes after HSCT critically depend on the degree of donor-recipient matching at the human leukocyte antigen (HLA) loci; a poorly matched transplant will trigger a graft-versus-host disease (GVHD) and increase mortality 2 . The most frequent allogeneic transplants are those in which the donor is an HLAidentical sibling 3,4 ; however, only 30% of patients who require a transplant have a compatible family donor, and with the reduction of children per family, this percentage is decreasing 5 . For patients without a suitable HLA-identical donor, a family-related donor as a source of hematoprogenitors for haploidentical-related hematopoietic stem cell transplantation (haplo-R-HSCT) represents a valid alternative 1 with immediate donor availability in almost all patients 6 .…”

Section: Introductionmentioning

confidence: 99%

Impact of HLA-DPB1 Matching on Clinical Outcomes after Haploidentical-Related Hematopoietic Stem Cell Transplantation

Jaime‐Pérez

Cancela-Murrieta

Salazar‐Cavazos

et al. 2020

RIC

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Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

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“…However, leukemia relapse still accounts for most deaths after transplantation. [1][2][3][4] Based on accumulating evidence, a minimal residual disease (MRD) assessment has crucial prognostic value for patients with AML in morphologic complete remission (CR) after receiving allo-HSCT. [5][6][7][8][9][10][11] However, questions remain unanswered, particularly regarding the optimal method for MRD detection in patients with AML, which encompasses a wide range of myeloid neoplasms with diverse abnormalities.…”

Section: Introductionmentioning

confidence: 99%

“…Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a curative treatment for acute myeloid leukemia (AML). However, leukemia relapse still accounts for most deaths after transplantation . Based on accumulating evidence, a minimal residual disease (MRD) assessment has crucial prognostic value for patients with AML in morphologic complete remission (CR) after receiving allo‐HSCT .…”

Section: Introductionmentioning

confidence: 99%

The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

Wang

Guo

Zhang

et al. 2019

Int J Lab Hematology

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Background The MRD status detected using multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) has crucial prognostic value for patients with acute myeloid leukemia (AML) in morphologic complete remission (CR). We designed a novel panel of antibodies to identify aberrant differentiation/maturation profiles of residual leukemia cells in patients who were not diagnosed at our institution, relapsed with an antigenic shift, or lack leukemia‐associated immunophenotypes. Methods We compared the MRD status detected using MFC and real‐time quantitative polymerase chain reaction (RT‐qPCR) in the same 158 bone marrow samples collected from 44 AML patients carrying leukemia‐specific fusion genes. The clinical performance of the MFC‐based MRD status was analyzed in 168 AML patients who exhibited morphologic CR (135) or active disease (33) before HSCT. Results Strong concordance was found between MFC‐based and RT‐qPCR‐based MRD status (κ = 0.868). Among the patients displaying CR, the positive MRD status detected using MFC was correlated with a worse prognosis [HRs (P values) for relapse, event‐free survival, and overall survival: 4.83 (<0.001), 2.23 (0.003), and 1.79 (0.049), respectively]; the prognosis was similar to patients with an active disease before HSCT. Patients with a positive MRD before HSCT might experience a benefit from developing chronic graft‐vs‐host disease. Conclusions The assessment of MRD using our self‐built different‐from‐normal AML‐MRD detection panel exhibited reliable sensitivity, specificity, and accuracy. In addition, patients with a positive MRD status before transplantation may have higher risk of relapse and worse survival.

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Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation

Cited by 15 publications

References 34 publications

HLA epitope mismatch in haploidentical transplantation is associated with decreased relapse and delayed engraftment

HLA epitope mismatch in haploidentical transplantation is associated with decreased relapse and delayed engraftment

Impact of HLA-DPB1 Matching on Clinical Outcomes after Haploidentical-Related Hematopoietic Stem Cell Transplantation

The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

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