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Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide Therapy vs Other Donor Transplantations in Adults With Hematologic Cancers: A Systematic Review and Meta-analysis
Gagelmann, N., Bacigalupo, A., Rambaldi, A., Hoelzer, D., Halter, J., Sanz, J., Bonifazi, F., Meijer, E., Itala-Remes, M., Markova, M., et al
JAMA oncology. 2019
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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 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.
2.
Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT
Shem-Tov, N., Peczynski, C., Labopin, M., Itala-Remes, M., Blaise, D., Labussiere-Wallet, H., Socie, G., Kroger, N., Mielke, S., Afanasyev, B., et al
Leukemia. 2019
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Editor's Choice
Abstract
Unmanipulated haploidentical allogeneic stem cell transplantation (Allo-SCT) has become an attractive alternative for patients lacking HLA-matched sibling or unrelated donors. However, data of outcome in ALL is still scarce. The outcomes of 1234 adult patients with ALL in first complete remission (CR1) who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was done between haploidentical donor (Haplo) (136 patients), matched unrelated donor (MUD 10/10) (809 patients), and mismatched unrelated donor (MMUD 9/10) (289 patients). Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the hazard ratio (HR) for LFS, OS, RI, NRM, AGVHD, and CGVHD were 1.1 (p = 0.7), 0.9 (p = 0.4), 1.35 (p = 0.2), 0.7 (p = 0.2), 1.1 (p = 0.8), and 0.8 (p = 0.2) for MUD, respectively, and 1.1 (p = 0.8), 1.0 (p = 1.0), 1.2 (p = 0.3), 0.8 (p = 0.4), 1.2 (p = 0.3), and 0.9 (p = 0.6) for MMUD, respectively. In conclusion, outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as a clinically relevant option for patients lacking a matched sibling donor.
PICO Summary
Population
Adult patients with acute lymphoblastic leukaemia in first complete remission (n=1234)
Intervention
Haploidentical transplantation (n=136)
Comparison
Matched unrelated donor (n=809) or Mismatched unrelated donor (n=289)
Outcome
Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10.