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Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407
Author(s) -
Salzer Wanda L.,
Jones Tamekia L.,
Devidas Meenakshi,
Hilden Joanne M.,
Winick Naomi,
Hunger Stephen,
Carroll William L.,
Camitta Bruce,
Dreyer ZoAnn E.
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24132
Subject(s) - medicine , cohort , daunorubicin , prednisone , pediatrics , dexamethasone , cohort study , leukemia
Background Infants (<366 days of age) with acute lymphoblastic leukemia (ALL) have a poor prognosis. Most treatment failures occur within 6–9 months of diagnosis, primarily from relapse. Procedure The Children's Oncology Group P9407 study was designed to test if early intensified treatment would improve outcome for infants with ALL. Due to a significant number of early deaths (< 90 days from enrollment), Induction therapy was amended three times. Cohorts 1 + 2 (n = 68), received identical Induction therapy except for reduced daunorubicin dose in Cohort 2. Cohort 3 (n = 141) received prednisone (40 mg/m 2 /day) instead of dexamethasone (10 mg/m 2 /day) and short infusion daunorubicin (30 minutes) instead of continuous infusion (48 hours), as well as additional supportive care measures throughout therapy. Results Early deaths occurred in 17/68 (25%) infants in Cohorts 1 + 2 and 8/141 (5.7%) infants in Cohort 3 ( P < 0.0001). Among infants ≤90 days of age at diagnosis, early death occurred in 10/17 (58.8%) in Cohorts 1 + 2 and 4/27 (14.8%) in Cohort 3 ( P = 0.006). Among infants >90 days of age at diagnosis, early death occurred in 7/51 (13.7%) in Cohorts 1 + 2 and 4/114 (3.5%) in Cohort 3 ( P = 0.036). Bacterial, viral, and fungal infections were more common in Cohorts 1 + 2 versus Cohort 3. Conclusions Early morbidity and mortality for infants with ALL were reduced by substitution of prednisone (40 mg/m 2 /day) for dexamethasone (10 mg/m 2 /day), the delivery of daunorubicin over 30 minutes instead of a continuous infusion for 48 hours, and the provision of more specific supportive care measures. Pediatr Blood Cancer 2012; 59: 834–839. © 2012 Wiley Periodicals, Inc.