title: 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.
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.
authors.affiliation: Berlin-Frankfurt-Münster Study Group, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Paola
authors.initials: P
authors.lastname: De Lorenzo
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.forename: Ian
authors.initials: I
authors.lastname: Hann
authors.forename: Giulio
authors.initials: G
authors.lastname: De Rossi
authors.forename: Maria
authors.initials: M
authors.lastname: Felice
authors.forename: Birgitte
authors.initials: B
authors.lastname: Lausen
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rubnitz
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Myriam
authors.initials: M
authors.lastname: Campbell
authors.forename: Chi Kong
authors.initials: CK
authors.lastname: Li
authors.forename: Ram
authors.initials: R
authors.lastname: Suppiah
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Ajay
authors.initials: A
authors.lastname: Vora
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000367:Age Factors; D018572:Disease-Free Survival; D015321:Gene Rearrangement; D018380:Hematopoietic Stem Cell Transplantation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007958:Leukocyte Count; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase