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Treatment Outcome and Prognostic Factors for Infants With Acute Lymphoblastic Leukemia Treated on Two Consecutive Trials of the Children's Cancer Group

From the Children's National Medical Center and George Washington University School of Medicine, Washington, DC; University of Southern California School of Medicine, Los Angeles, CA; Group Operations Center, Children's Cancer Group, Arcadia, CA; Children's Hospital of Philadelphia, Philadelphia, PA; Children's Hospital of Oakland, Oakland, CA; Indiana University School of Medicine, Bloomington, IN; University of Michigan, Ann Arbor, MI; Children's Hospital and Medical Center, Seattle, WA; University of Illinois, Chicago, IL; Primary Children's Medical Center, Salt Lake City, UT; Memorial Sloan-Kettering Cancer Center, New York, NY; University of California, Irvine, CA; University of Wisconsin, Madison, WI; Jefferson Medical College, Thomas Jefferson University, and Dupont Hospital for Children, Wilmington, DE; and Children's Cancer Group ALL Biology Reference Laboratory, Wayne Hughes Institute, St. Paul, MN.

Address reprint requests to Gregory H. Reaman, MD, Children's Cancer Group, PO Box 60012, Arcadia, CA 91066-6012; email greaman{at}cnmc.org

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols.

PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies.

RESULTS: Most patients (> 95%) achieved remission with induction therapy. The 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 improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 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 prognostic factors were age less than 3 months, WBC count of more than 50,000/µL, CD10 negativity, slow response to induction therapy, and presence of the 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 failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

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