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

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