Document Detail

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).
MedLine Citation:
PMID:  12199778     Owner:  NLM     Status:  MEDLINE    
We studied the effectiveness of risk-directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty-two cases (76.3%) had a rearranged MLL gene (MLL+) and were treated with remission induction therapy followed by sequential intensive chemotherapy, including multiple genotoxic agents (MLL9601 protocol). Haematopoietic stem cell transplantation (HSCT) was attempted if suitable donors were available. Thirteen infants (23.7%) were classified as MLL- and treated for 2.5 years with intensive chemotherapy for high-risk B-ALL (MLL9602 protocol). Complete remission was induced in 38 of the 42 infants (90.5%) with MLL+ ALL and in all 13 patients (100%) with MLL- disease. In the MLL+ subgroup, the estimated event-free survival (EFS) rate at 3 years post diagnosis was 34.0% +/- 7.5%, compared with 92.3% +/- 7.4% in the MLL- subgroup (overall comparison, P = 0.001 by log-rank analysis). Both age less than 6 months (hazard ratio = 6.87, 95% CI = 0.91-52.3; P = 0.013) and central nervous system (CNS) involvement at diagnosis (hazard ratio = 2.92 95% CI = 1.29-6.63; P = 0.015) were significant independent predictors of an inferior outcome. These findings indicate a strategic advantage in classifying infant ALL as either MLL+ or MLL- early in the clinical course and selecting therapy accordingly. Standard chemotherapy for high-risk B-lineage ALL appeared adequate for MLL- cases. Novel therapeutic initiatives are warranted for infants with MLL+ disease, particularly those with initial CNS leukaemic involvement or age less than 6 months, or both.
Keiichi Isoyama; Mariko Eguchi; Shigeyoshi Hibi; Naoko Kinukawa; Hiroji Ohkawa; Hajime Kawasaki; Yoshiyuki Kosaka; Takanori Oda; Megumi Oda; Takayuki Okamura; Shin-Ichiro Nishimura; Yasuhide Hayashi; Taijiro Mori; Masue Imaizumi; Shuki Mizutani; Ichiro Tsukimoto; Nanao Kamada; Eiichi Ishii
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  118     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-29     Completed Date:  2002-11-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  999-1010     Citation Subset:  IM    
Department of Paediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cytogenetic Analysis
DNA-Binding Proteins / genetics*
Disease-Free Survival
Follow-Up Studies
Gene Rearrangement*
Immunosuppressive Agents / therapeutic use
In Situ Hybridization, Fluorescence
Infant, Newborn
Myeloid-Lymphoid Leukemia Protein
Patient Selection
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*,  therapy*
Remission Induction
Risk Assessment
Stem Cell Transplantation
Transcription Factors*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Immunosuppressive Agents; 0/MLL protein, human; 0/Transcription Factors; 149025-06-9/Myeloid-Lymphoid Leukemia Protein

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