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.
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.
Mann
Georg
G
Berlin-Frankfurt-Münster Study Group, Austria.
Attarbaschi
Andishe
A
Schrappe
Martin
M
De Lorenzo
Paola
P
Peters
Christina
C
Hann
Ian
I
De Rossi
Giulio
G
Felice
Maria
M
Lausen
Birgitte
B
Leblanc
Thierry
T
Szczepanski
Tomasz
T
Ferster
Alina
A
Janka-Schaub
Gritta
G
Rubnitz
Jeffrey
J
Silverman
Lewis B
LB
Stary
Jan
J
Campbell
Myriam
M
Li
Chi Kong
CK
Suppiah
Ram
R
Biondi
Andrea
A
Vora
Ajay
A
Valsecchi
Maria Grazia
MG
Pieters
Rob
R
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
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase