Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)–rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study
- 14 October 2010
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 116 (15), 2644-2650
- https://doi.org/10.1182/blood-2010-03-273532
Abstract
To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia 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 of 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 = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 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 resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 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+ acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487.This publication has 31 references indexed in Scilit:
- Controversies of and Unique Issues in Hematopoietic Cell Transplantation for Infant LeukemiaTransplantation and Cellular Therapy, 2009
- Acute lymphoblastic leukemia in infancyPediatric Blood & Cancer, 2007
- Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study GroupLeukemia, 2007
- A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trialThe Lancet, 2007
- Acute lymphoblastic leukemia with t(4;11) in children 1 year and older: The ‘big sister’ of the infant disease?Leukemia, 2007
- The MLL recombinome of acute leukemiasLeukemia, 2006
- Infant acute lymphoblastic leukemia – combined cytogenetic, immunophenotypical and molecular analysis of 77 casesLeukemia, 2002
- Late effects in survivors of infant leukemiaLeukemia, 2000
- Biological and therapeutic aspects of infant leukemiaBlood, 2000
- Prednisone Response Is the Strongest Predictor of Treatment Outcome in Infant Acute Lymphoblastic LeukemiaBlood, 1999