title: Decreased induction morbidity and mortality following modification to induction therapy in infants with acute lymphoblastic leukemia enrolled on AALL0631: a report from the Children's Oncology Group.
abstract: BACKGROUND
  Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Intensification of therapy has resulted in fewer relapses but increased early deaths, resulting in failure to improve survival.
  
  
  METHODS
  AALL0631 is a Phase 3 study for infants (<366 days of age) with newly diagnosed ALL. Induction initially (Cohort 1) consisted of 3 weeks of therapy based on COG P9407. Due to excessive early mortality, induction was amended to a less intensive 5 weeks of therapy based on Interfant-99. Additionally, enhanced supportive care guidelines were incorporated with hospitalization during induction until evidence of marrow recovery and recommendations for prevention/treatment of infections (Cohort 2).
  
  
  RESULTS
  Induction mortality was significantly lower for patients in Cohort 2 (2/123, 1.6%) versus Cohort 1 (4/26, 15.4%; P = 0.009). All induction deaths were infection related except one due to progressive disease (Cohort 2). Sterile site infections were lower for patients in Cohort 2 (24/123, 19.5%) versus Cohort 1 (15/26, 57.7%; P = 0.0002), with a significantly lower rate of Gram positive infections during induction for patients in Cohort 2, P = 0.0002. No clinically significant differences in grades 3-5 non-infectious toxicities were observed between the two cohorts. Higher complete response rates were observed at end induction intensification for Cohort 2 (week 9, 94/100, 94%) versus Cohort 1 (week 7, 17/25, 68%; P = 0.0.0012).
  
  
  CONCLUSIONS
  De-intensification of induction therapy and enhanced supportive care guidelines significantly decreased induction mortality and sterile site infections, without decreasing complete remission rates.
authors.affiliation: U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland.
authors.forename: Wanda L
authors.initials: WL
authors.lastname: Salzer
authors.forename: Tamekia L
authors.initials: TL
authors.lastname: Jones
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: ZoAnn E
authors.initials: ZE
authors.lastname: Dreyer
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Raetz
authors.forename: Mignon L
authors.initials: ML
authors.lastname: Loh
authors.forename: Cindy Y
authors.initials: CY
authors.lastname: Wang
authors.forename: Paola
authors.initials: P
authors.lastname: De Lorenzo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Hilden
authors.forename: Patrick
authors.initials: P
authors.lastname: Brown
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality*; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality*
keywords: infant acute lymphoblastic leukemia; mortality