The Comparison of Unmanipulated Bone Marrow Versus Peripheral Blood Haploidentical Stem Cell Transplantation in Adult Acute Leukemia: A Systematic Review and Meta-Analysis

Abstract

Background:The use of peripheral blood stem cell source (PBSC) continues to grow in the setting of haploidentical hematopoietic stem cell transplantation (haplo-SCT), mainly due to the ease of collection and rapid peripheral blood count recovery. We conducted a systematic review and meta-analysis of the published literature to evaluate the outcomes of unmanipulated bone marrow (BM) and PB haplo-SCT for adult leukemia patients.Method:A comprehensive literature search of electronic databases (Medline, Embase, and Cochrane library) for studies published between 1 January 2004 to 24 June 2018 was conducted. We included the studies of unmanipulated BM and/or PB haplo-SCT in adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia ( ALL) . We excluded the studies which combined PB and BM stem cell sources and the studies which did not report the results of BM and PB haplo-SCT for ALL and AML separately. CMA software v.3 was used for the analysis. Heterogeneity among studies was assessed using the I2 test. Random-effect model was applied. Publication bias was assessed using funnel plots. Primary endpoints were engraftment, 2-year overall survival (OS), disease-free survival (DFS), relapse incidence (RI); grade II-IV, III-IV acute and chronic GVHD.Results: Out of 1548 publications, 3 studies (n = 672 patients; retrospective; multi-center) met our inclusion criteria. The sample size of the studies varied between 71 and 451 patients. The median follow-up ranged from 18 to 46 months. PB haplo-SCT was used in 191 patients (Ruggeri, A. et al. 2018) and BM haplo-SCT was used in 481 patients (Arcese, W. et al. 2015; Ruggeri, A. et al. 2018; Chiusolo, P. et al. 2018). Myeloablative (MA) conditioning was used in majority of patients. The pooled (95%CI) engraftment rate was 93% (88-95) in BM group and 95% (91-97) in PBSC group. The pooled estimates (95%CI) of BM studies showed a 2-year OS rate of 56.1% (51.6-60.4), 2-year DFS of 48.9% (43.5-54.2) and 2-year cumulative RI of 24.6%(20.7-29).There was no heterogeneity in BM group (I2=0%) for 2-year OS, DFS and RI. For PBSC group, the pooled estimates (95%CI) for 2-year OS, DFS and RI were 56 % (48.9-62.9; I2=0%), 54% (46.9-60.9; I2=0%) and 22% (16.7-28.4; I2=0%), respectively. Incidences of grade II-IV, grade III-IV aGVHD and cGVHD from a pooled analysis (95%CI) were 23.1% (17.2-30.3; I2=55%), 5.4% (3.4-8.3; I2=16%) and 19.5% (9.7-35.3; I2=88%) for BM group in comparison to 38% (31.4-45.1; I2=0%), 14% (9.8-19.7; I2=0%) and 32% (25.8-38.9; I2=0%) for PBSC group. Pooled estimates were shown in figure 1.Conclusions:In this analysis, higher pooled rates of grade II-IV aGVHD (38% vs 23.1%), III-IV aGVHD (14% vs 5.4%) and cGVHD (32% vs 19.5%) were observed in PBSC group vs BM group, respectively. Based on comparable OS, DFS and RI, PB haplo-SCT appears to be a good alternative option for adult AML and ALL patients. Large prospective randomized controlled trials are required to confirm these results. DisclosuresNo relevant conflicts of interest to declare.