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Original Investigation
October 17, 2019

Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide Therapy vs Other Donor Transplantations in Adults With Hematologic Cancers: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 2Fondazione Policlinico Universitario A. Gemelli Institute of Scientific Research and Treatment, Universita' Cattolica del Sacro Cuore, Rome, Italy
  • 3Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
  • 4Goethe University Hospital, Department of Medicine II, Hematology/Oncology, Frankfurt am Main, Germany
  • 5Division of Hematology, Basel University Hospital, Basel, Switzerland
  • 6Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
  • 7Department of Hematology, L and A Seràgnoli, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
  • 8Amsterdam University Medical Center, Vrije Universiteit, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands
  • 9Turku University Hospital, Turku, Finland
  • 10Institute for Hematology and Blood Transfusion, Hospital Na Bulovce, Prague, Czech Republic
  • 11Hospital Clinico Universitario-INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain
JAMA Oncol. Published online October 17, 2019. doi:https://doi.org/10.1001/jamaoncol.2019.3541
Key Points

Question  What are the outcomes of haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy compared with other transplant types in adults with hematologic cancers?

Findings  In this meta-analysis of 30 studies including 22 974 patients, the use of haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy appeared to show increased all-cause mortality compared with matched related donors, similar all-cause mortality compared with matched unrelated donors, and reduced all-cause mortality compared with mismatched unrelated donors. Relapse appeared to be increased in lymphoma and similar in acute leukemia compared with matched unrelated donors.

Meaning  Haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy may be preferred to mismatched unrelated donors, and prospective comparisons with matched donors are needed.

Abstract

Importance  Use of haploidentical (HAPLO) stem cell transplantation with posttransplant cyclophosphamide is rapidly increasing in adults with hematologic cancers. However, its specific role compared with other transplant strategies has yet to be identified.

Objective  To synthesize the existing evidence regarding outcomes of stem cell transplantations comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from matched related donors (MRDs), matched unrelated donors (MUDs), or mismatched unrelated donors (MMUDs).

Data Sources  PubMed, Cochrane Library, ClinicalTrials.gov, and meeting abstracts were searched for the key words haploidentical and cyclophosphamide from inception through March 1, 2019.

Study Selection  Studies comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from other donors in adults with hematologic cancers were eligible for meta-analysis.

Data Extraction and Synthesis  Pooled odds ratios (ORs) and 95% CIs were calculated using a random-effects model.

Main Outcomes and Measures  Main outcomes were all-cause mortality, nonrelapse mortality, and relapse.

Results  A total of 30 studies including 22 974 participants were analyzed. HAPLO stem cell transplantation with posttransplant cyclophosphamide therapy was associated with increased all-cause mortality compared with MRDs (OR, 1.17; 95% CI, 1.05-1.30), similar all-cause mortality compared with MUDs (OR, 1.06; 95% CI, 0.96-1.18), and reduced all-cause mortality compared with MMUDs (OR, 0.75; 95% CI, 0.61-0.92). Regarding nonrelapse mortality, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with worse outcomes compared with MRDs (OR, 1.20; 95% CI, 1.04-1.40) but better outcomes compared with MUDs (OR, 0.75; 95% CI, 0.61-0.92) and MMUDs (OR, 0.51; 95% CI, 0.25-1.02). In terms of relapse, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with similar outcome compared with MRDs (OR, 1.01; 95% CI, 0.86-1.17) and MMUDs (OR, 1.06; 95% CI, 0.77-1.47) but showed increased relapse compared with MUDs (OR, 1.20; 95% CI, 1.03-1.40).

Conclusions and Relevance  Results of this meta-analysis suggest that MRDs, if available, remain the optimal donors regarding mortality and HAPLO stem cell transplantation with posttransplant cyclophosphamide may be preferred over MMUDs. Prospective comparisons with MUDs are needed.

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