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


METHODS
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.
Department of Pediatrics, Aichi Medical University, Aichi-gun, Aichi-ken, Japan.
Kazutaka
K
Yamaji
Tomomi
T
Okamoto
Shohei
S
Yokota
Arata
A
Watanabe
Yasuo
Y
Horikoshi
Keiko
K
Asami
Atsushi
A
Kikuta
Nobuyuki
N
Hyakuna
Yutaka
Y
Saikawa
Junichi
J
Ueyama
Tsutomu
T
Watanabe
Masahiko
M
Okada
Takashi
T
Taga
Hirokazu
H
Kanegane
Kazuhiro
K
Kogawa
Motoaki
M
Chin
Asayuki
A
Iwai
Takeshi
T
Matsushita
Yasuto
Y
Shimomura
Toshinori
T
Hori
Masahito
M
Tsurusawa
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome