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

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 22974 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. This systematic review and meta-analysis assesses outcomes of stem cell transplantations using the haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy compared with other mismatched or matched donor transplants in adult patients with hematologic cancers. 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 22974 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.