Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected]. J Clin Oncol 2008 Aug 20;26(24):3971-8
Date
08/20/2008Pubmed ID
18711187Pubmed Central ID
PMC2654313DOI
10.1200/JCO.2008.16.1414Scopus ID
2-s2.0-50549083190 (requires institutional sign-in at Scopus site) 197 CitationsAbstract
PURPOSE: Treatment of childhood relapsed acute lymphoblastic leukemia (ALL) remains a significant challenge. The goal of the Children's Oncology Group (COG) AALL01P2 study was to develop a safe and active chemotherapy reinduction platform, which could be used to evaluate novel agents in future trials.
PATIENTS AND METHODS: One hundred twenty-four patients with ALL and first marrow relapse received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse (ER; < 36 months from initial diagnosis) and 55 with late relapse (LR). Minimal residual disease (MRD) was measured by flow cytometry after each treatment block.
RESULTS: Second complete remission (CR2) rates at the end of block 1 in 117 assessable patients were 68% +/- 6% for ER (n = 63) and 96% +/- 3% for LR (n = 54; P < .0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve CR2. Among patients in CR2, MRD greater than 0.01% was detected at the end of block 1 in 75% +/- 7% of ER (n = 36) versus 51% +/- 8% of LR (n = 43; P = .0375) and 12-month event-free survival was 80% +/- 7% versus 58% +/- 7% in MRD-negative versus positive patients (P < .0005). Blocks 2 and 3 of therapy resulted in reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1. Toxicity was acceptable during all three blocks with five deaths (4%) from infections.
CONCLUSION: The AALL01P2 regimen is a tolerable and active reinduction platform, suitable for testing in combination with novel agents in B-precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD measurements were feasible and prognostic of outcome.
Author List
Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, Camitta BM, Gaynon PS, Carroll WLMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Antineoplastic Combined Chemotherapy Protocols
Bone Marrow Neoplasms
Central Nervous System Neoplasms
Child
Child, Preschool
Cytarabine
Dexamethasone
Doxorubicin
Female
Flow Cytometry
Humans
Idarubicin
Infant
Leukemia, T-Cell
Leukemic Infiltration
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prednisone
Remission Induction
