Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukaemia: results from the Interfant-99 Study

To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia (ALL) and rearrangements of the mixed-lineageleukemia gene (MLL+) we compared the outcome of MLL+ patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL+. Among the 277/297 MLL+ patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P=0.03). However, the advantage was restricted to a subgroup with two additional unfavourable prognostic features: age <6 months and either poor response to steroids at day 8 or leukocytes ≥300 G/L. Ninety-seven/297 MLL+ patients (33%) had such high-risk criteria, with 87 achieving CR. In this group HSCT was associated with a 64% reduction in the risk of failure due to relapse or death in CR (HR=0.36, 95% CI: 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL+ ALL carrying further poor prognostic factors. The trial was registered with http://ClinicalTrials.gov (NCT 00015873) and at http://controlledtrials. com (ISRCTN24251487).