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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
7044258 - Chlorpromazine and propranolol extend survival of infant mice inoculated with enterotox...
9261598 - Morphometric study of the small bowel mucosa in infants with diarrhea due to enteropath...
22575248 - Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containi...
11498698 - typing of enteric adenoviruses in feces of infants with diarrhea
9987738 - Risk factors and outcomes associated with nuchal cord. a population-based study.
7377158 - Acute caffeine overdose in the neonate.
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    
Affiliation:
Department of Paediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan. isoyama@showa-university-fujigaoka.gr.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cytogenetic Analysis
DNA-Binding Proteins / genetics*
Disease-Free Survival
Follow-Up Studies
Gene Rearrangement*
Humans
Immunosuppressive Agents / therapeutic use
In Situ Hybridization, Fluorescence
Infant
Infant, Newborn
Japan
Myeloid-Lymphoid Leukemia Protein
Patient Selection
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*,  therapy*
Proto-Oncogenes*
Remission Induction
Risk Assessment
Stem Cell Transplantation
Transcription Factors*
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Immunosuppressive Agents; 0/MLL protein, human; 0/Transcription Factors; 149025-06-9/Myeloid-Lymphoid Leukemia Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Increased angiogenesis in bone marrow of children with acute lymphoblastic leukaemia has no prognost...
Next Document:  Molecular characterization of a new recombination of the SIL/TAL-1 locus in a child with T-cell acut...