Stem-Cell Transplantation in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia in First Complete Remission: A Prospective Multicenter Trial Comparing Haploidentical Donors with Identical Sibling Donors

Abstract

Purpose and design The effect of HLA-identical sibling donor (ISDs) haematopoietic stem cell transplantation (HSCT) on adults with high-risk acute lymphoblastic leukaemia (ALL) in the first complete remission (CR1) has been established. Our recent single-institute, retrospective study showed that haploidentical HSCT was superior to chemotherapy alone for patients with high-risk ALL in CR1. To test the hypothesis that haploidentical HSCT would be a valid option as post-remission therapy for ALL patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multi-centre study.Patients Between July 2010 and Dec 2013, 186 patients with Philadelphia-negative high-risk ALL were biologically randomized to undergo un-manipulated HIDs (103 patients) or ISDs HSCT (83 patients) according to donor availability.Results Among HIDs and ISDs recipients, the 3-year disease free survival (DFS) rate was 68% and 64% (P =.56), respectively; overall survival (OS) rate was 75% and 69% (P = .51, respectively; cumulative incidences of relapse were 18% and 24% (P = .30), and those of the non-relapse-mortality (NRM) were 13% and 11% (P = .84), respectively. The 28-d myeloid recovery rates were both 99% in each group; the incidences of severe acute graft-versus-host-disease (GVHD) and chronic GVHD were also comparable between the two groups. Among recipients of transplantations from HIDs, no significant differences in DFS, OS, or NRM were observed between 3/6 and 4-5/6 matched grafts; in contrast, maternal donor was related with lower OS compared with other donor sources (P = .04); limited chronic GVHD was associated with better DFS (P = .01). The stem cell source had no effect on DFS.Conclusion Un-manipulated haploidentical-HSCT achieves outcomes similar to those of ISD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation was proved to be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. (Chictr.org.cn number ChiCTR-OCH-10000940)TableResults of multivariate analysis of outcomesOutcomeHazard ratio (95%Confidence interval)p valueDisease free survivalHaploidentical vs Identical sibling0.88 (0.50-1.53).65Patient age <30 vs >30 years0.74 (0.42-1.28).28Patient sex male vs female1.13 (0.55-2.30).74Time to transplant <6 vs >6 months1.48 (0.86-2.56).16Female-to-male vs other sex pair0.95(0.52-1.75).86Limited chronic GVHD vs no or extended0.59 (0.29-1.17).13Overall survivalHaploidentical vs Identical sibling0.91 (0.50-1.70).77Patient age <30 vs >30 years0.60 (0.33-1.11).11Patient sex male vs female1.13 (0.55-2.30).74Time to transplant <6 vs >6 months1.64 (0.89-3.01).11Female-to-male vs other sex pair1.22 (0.64-2.31).54Limited chronic GVHD vs no or extended0.59 (0.27-1.28).18RelapseHaploidentical vs Identical sibling0.67(0.33-1.36).27Patient age <30 vs >30 years1.06 (0.50-2.28).87Patient sex male vs female1.52 (0.64-3.62).35Time to transplant <6 vs >6 months1.42 (0.69-2.90).33Female-to-male vs other sex pair0.61(0.26-1.45).27Limited chronic GVHD vs no or extended0.65 (0.26-1.62).36Non-Relapse-MortalityHaploidentical vs Identical sibling1.38(0.58-3.35).46Patient age <30 vs >30 years0.47 (0.19-1.17).11Patient sex male vs female0.66 (0.19-2.33).52Time to transplant <6 vs >6 months1.66 (0.70-3.92).25Female-to-male vs other sex pair1.53(0.64-3.69).34Limited chronic GVHD vs no or extended0.63 (0.21-1.86).40 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.