Nico Gagelmann1, Andrea Bacigalupo2, Alessandro Rambaldi3, Dieter Hoelzer4, Jörg Halter5, Jaime Sanz6, Francesca Bonifazi7, Ellen Meijer8, Maija Itälä-Remes9, Markéta Marková10, Carlos Solano11, Nicolaus Kröger1. 1. Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2. Fondazione Policlinico Universitario A. Gemelli Institute of Scientific Research and Treatment, Universita' Cattolica del Sacro Cuore, Rome, Italy. 3. Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. 4. Goethe University Hospital, Department of Medicine II, Hematology/Oncology, Frankfurt am Main, Germany. 5. Division of Hematology, Basel University Hospital, Basel, Switzerland. 6. Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. 7. Department of Hematology, L and A Seràgnoli, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy. 8. Amsterdam University Medical Center, Vrije Universiteit, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands. 9. Turku University Hospital, Turku, Finland. 10. Institute for Hematology and Blood Transfusion, Hospital Na Bulovce, Prague, Czech Republic. 11. Hospital Clinico Universitario-INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.
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.
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.
Authors: Brian Kornblit; Barry E Storer; Niels S Andersen; Michael B Maris; Thomas R Chauncey; Effie W Petersdorf; Ann E Woolfrey; Mary E D Flowers; Rainer Storb; David G Maloney; Brenda M Sandmaier Journal: Blood Date: 2020-09-24 Impact factor: 22.113
Authors: Dennis L Cooper; Jacqueline Manago; Vimal Patel; Dale Schaar; Tracy Krimmel; Mary Kate McGrath; Anne Tyno; Yong Lin; Roger Strair Journal: Bone Marrow Transplant Date: 2020-12-01 Impact factor: 5.483
Authors: R Parody; I Sánchez-Ortega; A Mussetti; B Patiño; M Arnan; H Pomares; E González-Barca; S Mercadal; C Boqué; C Maluquer; I Carro; M Peña; V Clapés; S Verdesoto; G Bustamante; A C Oliveira; C Baca; E Cabezudo; C Talarn; L Escoda; S Ortega; N García; M Isabel González-Medina; Mar Sánchez-Salmerón; C Fusté; J Villa; E Carreras; E Domingo-Domènech; A Sureda Journal: Bone Marrow Transplant Date: 2021-10-28 Impact factor: 5.483