Transplantation in children and adolescents with acute lymphoblastic leukemia from a matched donor versus an hla-identical sibling: Is the outcome comparable? Results from the international bfm all sct 2007 study
Children with acute lymphoblastic leukaemia, receiving allo-transplantation in 10 countries. (n=348).
Intervention
HLA-identical sibling donor (MSD) (n=138).
Comparison
Matched donor (MD) (n=210).
Outcome
The 4-year event-free survival, overall survival, cumulative incidence of relapse and non-relapse mortality were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD than in MSD recipients and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood than in bone marrow recipients. Compared with the absence of aGVHD, grade I-II was associated with a lower risk of failure and grade III-IV with a higher risk of failure and non-leukemic death, despite a lower risk of relapse. Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of non-leukemic death.
Abstract
INTRODUCTION Eligibility criteria for hematopoietic stem cell transplantation (SCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment and type of available donor; as the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. METHODS A total of 138 children and adolescents transplanted from HLA-identical siblings (MSD) and 210 from
matched donors (MD) (median 9 years, 68% male) in 10 countries were enrolled within the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in pediatric ALL. RESULTS The 4-year event-free survival (65%+/-5 vs 61%+/-4; p-value 0.287), overall survival (72%+/-4 vs 68%+/-4; p-value 0.235), cumulative incidence of relapse (24%+/-4 vs 25%+/-3; p-value 0.658) and non-relapse mortality (10%+/-3 vs 14%+/-3; p-value 0.212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD than in MSD recipients (HR 0.38, p-value 0.002) and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood than in bone marrow recipients (HR 2.06, p-value 0.026). Compared with the absence of aGVHD, grade I-II was associated with a lower risk of failure (HR 0.63, p-value 0.042) and grade III-IV with a higher risk of failure (HR 1.85, p-value 0.020) and non-leukemic death (HR 8.76, p-value <0.0001), despite a lower risk of relapse (HR 0.32, p-value 0.021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of non-leukemic death (HR 8.12, p-value <0.0001). CONCLUSIONS Since the outcome of transplantation from a matched donor was not inferior to transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and, possibly, in other malignancies. Bone marrow should be the preferred stem cell source and the addition of MTX should be considered in MSD recipients.
PICO Summary