title: Intensified therapy for infants with acute lymphoblastic leukemia: results from the Dana-Farber Cancer Institute Consortium.
abstract: BACKGROUND
  Infants with acute lymphoblastic leukemia (ALL) have a very poor prognosis. Since 1985, we have intensified therapy for infants with ALL by including a month of high dose multiagent chemotherapy after remission induction.
  
  
  METHODS
  Between 1985 and 1995, we treated 23 infants (age < 12 months). We compared the presenting characteristics and outcomes of these infants with the 11 infants treated on our protocols between 1973 and 1985, an era prior to the intensification of therapy. Available bone marrow samples from infants treated since 1985 were analyzed for the presence of MLL gene rearrangements by Southern blot analyses and for TEL-AML1 gene fusion by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  With a median follow-up of 5.6 years, the 50-month event free survival (EFS) (+/- standard error) for the 23 infants was 54 +/- 11%, a significant improvement (P = 0.001) compared with the outcome for the 11 infants treated on our protocols prior to 1985 (EFS = 9 +/- 9%). Of the seven infants found to have a rearranged MLL gene, three (43%) remained in first complete remission. None of the nine infant bone marrow specimens tested had evidence of TEL-AML1 gene fusion. The intensified therapy was complicated by a high incidence of infections, including septicemia in 52% of patients and Pneumocystis carinii pneumonitis in 22% of patients. Late effects identified in the 13 long term survivors (median age, 6 years) included developmental delay and learning disabilities of varying severity (82% of evaluable patients), asymptomatic cataracts (67%), asymptomatic echocardiographic abnormalities (30%), obesity (27%), and short stature (18%).
  
  
  CONCLUSIONS
  Intensification of therapy significantly improved the EFS of infants with ALL compared with previous, less intensive regimens and with the experience of other investigators. Future treatment for infants should attempt to improve efficacy while minimizing toxicity.
authors.affiliation: Children's Hospital, the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Silverman
authors.forename: T W
authors.initials: TW
authors.lastname: McLean
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: M J
authors.initials: MJ
authors.lastname: Donnelly
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
authors.forename: N J
authors.initials: NJ
authors.lastname: Tarbell
authors.forename: S E
authors.initials: SE
authors.lastname: Sallan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D050676:Core Binding Factor Alpha 2 Subunit; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D011519:Proto-Oncogenes; D012074:Remission Induction; D015996:Survival Rate; D014157:Transcription Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D001215:Asparaginase; D050676:Core Binding Factor Alpha 2 Subunit; D003561:Cytarabine; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D015122:Mercaptopurine; D008727:Methotrexate; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D014750:Vincristine; C497422:KMT2A protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein