Minimal residual disease-based augmented therapy in childhood acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

Abstract

BACKGROUND:

The majority of minimal residual disease (MRD)-positive patients with acute lymphoblastic leukemia (ALL) have poor outcomes. The ALL2000 study was performed to evaluate the efficacy of augmented chemotherapy based on MRD-restratification in childhood ALL.

PROCEDURE:

Between 2000 and 2004, 305 eligible patients with precursor B or T-cell ALL were enrolled in the ALL2000 study. The ALL941-based therapy protocol utilized PCR MRD assays using Immunoglobulin and T-cell receptor gene rearrangements. They were initially stratified into three risk-groups according to leukocyte count and age, and MRD levels were measured at weeks 5 (TP1) and 12 (TP2) for a second stratification. From week 14, patients with MRD levels ≥ 10(-3) received an increase in therapy (one risk group higher), while the remainder continued to receive the initial risk-adapted therapy.

RESULTS:

The overall 5-year event-free survival (EFS) rate for ALL2000 was 79.7 ± 2.4%. MRD stratification was feasible for 234 of 301 patients (77%) who achieved complete remission. The EFS rate of the MRD stratifiable (MRD) group was 82.5 ± 2.6%, considerably superior to the 74.7 ± 5.7% of MRD non-stratifiable (Non-MRD) group (P = 0.084) and the 74.4 ± 2.1% for ALL 941 (P = 0.012). MRD-positive patients at TP2 showed inferior outcomes as compared with MRD-negative cases, but the difference did not reach a statistically significant level in any risk groups or immunophenotypes.

CONCLUSIONS:

These results suggest that augmented therapy for MRD-positive patients at TP2 contributed to better outcomes of the ALL2000 study.

• Authors: Kazutaka Yamaji, Tomomi Okamoto, Shohei Yokota, Arata Watanabe, Yasuo Horikoshi, Keiko Asami, Atsushi Kikuta, Nobuyuki Hyakuna, Yutaka Saikawa, Junichi Ueyama, Tsutomu Watanabe, Masahiko Okada, Takashi Taga, Hirokazu Kanegane, Kazuhiro Kogawa, Motoaki Chin, Asayuki Iwai, Takeshi Matsushita, Yasuto Shimomura, Toshinori Hori, Masahito Tsurusawa, Japanese Childhood Cancer Leukemia Study Group
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 55 Issue 7 Pg. 1287-95 (Dec 15 2010) ISSN: 1545-5017 [Electronic] United States
• PMID: 20535816 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Wiley-Liss, Inc.

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Disease-Free Survival
• Female
• Humans
• Infant
• Male
• Neoplasm, Residual
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (classification, drug therapy, mortality, pathology)
• Prognosis
• Risk Factors
• Survival Rate
• Treatment Outcome