Haploidentical Transplantation with Post-Transplant Cyclophosphamide versus Unrelated Donor Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Abstract

Hematopoietic stem cell transplantation (HSCT) is the standard treatment for patients with high-risk hematologic malignancies. Only approximately 25% of siblings are HLA-matched, and thus alternative donors-unrelated or haploidentical-are usually the only options available. This meta-analysis aimed to compare haploidentical HSCT with post-transplantation cyclophosphamide and unrelated donor (URD) HSCT. We searched the PubMed and Cochrane databases for pertinent studies indexed between 2008 and 2018. Twenty observational studies (with a total of 1783 haploidentical HSCT recipients and 6077 URD HSCT recipients) were included. Results for overall survival, graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and relapse incidence were pooled. Measures of association used were hazard ratios and risk differences. The median age was 51 years for haploidentical transplant recipients and 52 years for URD transplant recipients. Peripheral blood stem cell (PBSC) grafts were more frequent in the URD transplant recipients (85%) than in the haploidentical transplant recipients (31%). Overall survival was not different between the 2 groups. NRM was lower for haploidentical transplantation. All forms of GVHD (acute grades II-IV and III-IV and moderate, severe, and extensive chronic) were lower with haploidentical donor HSCT. The risk of chronic GVHD was fairly proportional to the differential use of PBSC grafts across studies, however. All included studies were retrospective, representing the major limitation of this meta-analysis. In conclusion, haploidentical HSCT for hematologic malignancies achieved the same overall survival as URD HSCT, with a lower incidence of GVHD and NRM. The increased frequency of PBSC use in the unrelated donor group could partially explain the higher cGVHD rate. Haploidentical transplantation with post-transplantation cyclophosphamide should strongly be considered as the first option for adult patients with hematologic malignancies who do not have matched sibling donors in experienced centers. This systematic review has been registered at PROSPERO (65790).

Haploidentical stem cell transplantation vs matched unrelated donor transplantation in adults with hematologic malignancies: a systematic review and meta-analysis

“…Recently, Arcuri et al [37] performed a meta-analysis to compare clinical outcome of Haplo-SCT with MUD-SCT. They concluded that Haplo-SCT for hematologic malignancies achieved the same overall survival as MUD-SCT, with a lower incidence of GVHD and NRM, and advocated that Haplo-SCT with PTCy should strongly be considered as the first option for adult patients with hematologic malignancies who do not have matched sibling donors in experienced centers.…”

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

“…In fact, aGvHD incidence varies from 40% for HLA-identical siblings [6] to 80% for HLAmismatched unrelated donors [2,13]. Only approximately 25% of siblings are HLA-matched, and usually, the only alternatives are unrelated or haploidentical donors [39]. A recent study has reported that post-transplant cyclophosphamide in HLA-haploidentical HSCT is associated with low rates of severe graft-versus-host disease and its efficacy is comparable with HLA-matched HSCT [40].…”

“…Table S5 shows the number of patients with aGvHD for individual studies which report the grade and organs implicated (see Additional file, pp. [38][39][40]. Most of the included patients suffered grade III-IV (82.99%).…”

Posttransplant cyclophosphamide as GVHD prophylaxis for peripheral blood stem cell HLA-mismatched unrelated donor transplant

“…acute/chronic graft-versus-host disease (GVHD) and nonrelapse mortality (NRM), particularly when the graft source is peripheral blood stem cells (PBSCs). 3,5,9,10 We and others have previously reported encouraging results with tacrolimus/sirolimus-based GVHD prophylaxis after MUD-HCT. 6,11,12 Results from our earlier single institution analysis of tacrolimus/sirolimus-based GVHD prophylaxis after MUD and MMUD HCT showed that relative to MUD, MMUD-HCT is associated with significantly lower overall survival (OS), primarily because of increased NRM associated with GVHD and infections.…”