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

• Published in: Blood 2010-10, Vol.116 (15), p.2644-2650
• Main Authors: Mann, Georg, Attarbaschi, Andishe, Schrappe, Martin, De Lorenzo, Paola, Peters, Christina, Hann, Ian, De Rossi, Giulio, Felice, Maria, Lausen, Birgitte, LeBlanc, Thierry, Szczepanski, Tomasz, Ferster, Alina, Janka-Schaub, Gritta, Rubnitz, Jeffrey, Silverman, Lewis B., Stary, Jan, Campbell, Myriam, Li, Chi Kong, Suppiah, Ram, Biondi, Andrea, Vora, Ajay, Valsecchi, Maria Grazia, Pieters, Rob
• Format: Article
• Language: English
• Subjects: Age Factors; Biological and medical sciences; Disease-Free Survival; Gene Rearrangement; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Histone-Lysine N-Methyltransferase; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocyte Count; Medical sciences; Myeloid-Lymphoid Leukemia Protein - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prognosis; Risk Factors; Survival Analysis; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-03-273532

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.