Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group

Purpose: Infants represent a very poor risk group for acute lymphoblastic l eukemia (ALL). We report treatment outcome for such patients treated with i ntensive therapy on consecutive Children's Cancer Group (CCG) protocols. Patients and Methods: Between 1984 and 1993, infants with newly diagnosed A LL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Pa stconsolidation therapy was more intensive on CCG-1883. On both studies, pr ophylactic treatment of the CNS included both high-dose systemic chemothera py and intrathecal therapy in contrast to whole-brain radiotherapy, which w as used in earlier studies. Results: Most patients (> 95%) achieved remission with induction therapy. T he most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG-1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG-1883. Both studies represent an improve ment compared with a 22% (SE = 5.1%) event-free survival for historical con trols. Four-year cumulative probabilities of any marrow relapse or an isola ted CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-1 07 and 50%. (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prog nostic factors were age less than 3 months, WBC count of more than 50,000/m u L, CD10 negativity, slow response ta induction therapy and presence of th e translocation t(4;11). Conclusion: Outcome for infants on CCG-107 and CCG-1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failur e. Isolated CNS relapse rates are low, indicating that intrathecal chemothe rapy combined with very-high-dose systemic therapy provider adequate protec tion of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies. (C) 1999 by American Society of Clinical Oncology.