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
Authors: Wang Yu , Depei Wu , Liu Qifa , Xu Lan-Ping , Zhang Xiao-Hui , Huang Xiao-Jun 
Published: October 2019

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)
Table. Results of multivariate analysis of outcomes Outcome Hazard ratio (95%Confidence interval) p value Disease free survival Haploidentical vs Identical sibling 0.88 (0.50-1.53) .65 Patient age <30 vs >30 years 0.74 (0.42-1.28) .28 Patient sex male vs female 1.13 (0.55-2.30) .74 Time to transplant <6 vs >6 months 1.48 (0.86-2.56) .16 Female-to-male vs other sex pair 0.95(0.52-1.75) .86 Limited chronic GVHD vs no or extended 0.59 (0.29-1.17) .13 Overall survival Haploidentical vs Identical sibling 0.91 (0.50-1.70) .77 Patient age <30 vs >30 years 0.60 (0.33-1.11) .11 Patient sex male vs female 1.13 (0.55-2.30) .74 Time to transplant <6 vs >6 months 1.64 (0.89-3.01) .11 Female-to-male vs other sex pair 1.22 (0.64-2.31) .54 Limited chronic GVHD vs no or extended 0.59 (0.27-1.28) .18 Relapse Haploidentical vs Identical sibling 0.67(0.33-1.36) .27 Patient age <30 vs >30 years 1.06 (0.50-2.28) .87 Patient sex male vs female 1.52 (0.64-3.62) .35 Time to transplant <6 vs >6 months 1.42 (0.69-2.90) .33 Female-to-male vs other sex pair 0.61(0.26-1.45) .27 Limited chronic GVHD vs no or extended 0.65 (0.26-1.62) .36 Non-Relapse-Mortality Haploidentical vs Identical sibling 1.38(0.58-3.35) .46 Patient age <30 vs >30 years 0.47 (0.19-1.17) .11 Patient sex male vs female 0.66 (0.19-2.33) .52 Time to transplant <6 vs >6 months 1.66 (0.70-3.92) .25 Female-to-male vs other sex pair 1.53(0.64-3.69) .34 Limited chronic GVHD vs no or extended 0.63 (0.21-1.86) .40
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.