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

OutcomeHazard 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 
OutcomeHazard 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 
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Figure 1.
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Disclosures

No relevant conflicts of interest to declare.

Topics:
acute lymphocytic leukemia, complete remission, donors, relationship - sibling, stem cells, transplantation, hematopoietic stem cell transplantation, graft-versus-host disease, chronic, hyperimmunoglobulin d with periodic fever, disease remission

Author notes

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Asterisk with author names denotes non-ASH members.

© 2015 by The American Society of Hematology
2015
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