Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000)

• Published in: Leukemia Vol. 24; no. 2; pp. 320 - 334
• Main Authors: Silverman, L B, Stevenson, K E, O'Brien, J E, Asselin, B L, Barr, R D, Clavell, L, Cole, P D, Kelly, K M, Laverdiere, C, Michon, B, Schorin, M A, Schwartz, C L, O'Holleran, E W, Neuberg, D S, Cohen, H J, Sallan, S E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2010; Nature Publishing Group
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adolescent; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase; Cancer; Cancer Research; Chemotherapy; Child; Child, Preschool; Children; Clinical trials; Combined Modality Therapy; Consortia; Corticosteroids; Critical Care Medicine; Diagnosis; Drug therapy; educational-report; Female; Follow-Up Studies; Health aspects; Hematology; Humans; Immunophenotyping; Infant; Infant, Newborn; Injury prevention; Intensive; Internal Medicine; Leukemia; Lymphatic leukemia; Lymphocytes T; Male; Medicine; Medicine & Public Health; Oncology; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Radiation; Radiation standards; Razoxane; Remission Induction; Risk Factors; Survival; Survival Rate; Time Factors; Toxicity; Treatment Outcome; Vincristine; United States; anthracycline; acute lymphoblastic leukemia; asparaginase; long-term follow-up
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.253

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20–30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0–18 years were treated on four consecutive protocols: 85-01 (1985–1987), 87-01 (1987–1991), 91-01 (1991–1955) and 95-01 (1996–2000). The 10-year event-free survival (EFS)±s.e. by protocol was 77.9±2.8% (85-01), 74.2±2.3% (87-01), 80.8±2.1% (91-01) and 80.5±1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s ( P =0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79–85% for T-cell ALL patients and 75–78% for adolescents (age 10–18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.