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.
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: Leonid Karawajew; Michael Dworzak; Richard Ratei; Peter Rhein; Giuseppe Gaipa; Barbara Buldini; Giuseppe Basso; Ondrej Hrusak; Wolf-Dieter Ludwig; Günter Henze; Karl Seeger; Arend von Stackelberg; Ester Mejstrikova; Cornelia Eckert Journal: Haematologica Date: 2015-05-22 Impact factor: 9.941
Authors: Lynda M Vrooman; Traci M Blonquist; Marian H Harris; Kristen E Stevenson; Andrew E Place; Sarah K Hunt; Jane E O'Brien; Barbara L Asselin; Uma H Athale; Luis A Clavell; Peter D Cole; Kara M Kelly; Caroline Laverdiere; Jean-Marie Leclerc; Bruno Michon; Marshall A Schorin; Maria Luisa Sulis; Jennifer J G Welch; Donna S Neuberg; Stephen E Sallan; Lewis B Silverman Journal: Blood Adv Date: 2018-06-26
Authors: Michael J Borowitz; Brent L Wood; Meenakshi Devidas; Mignon L Loh; Elizabeth A Raetz; Wanda L Salzer; James B Nachman; Andrew J Carroll; Nyla A Heerema; Julie M Gastier-Foster; Cheryl L Willman; Yunfeng Dai; Naomi J Winick; Stephen P Hunger; William L Carroll; Eric Larsen Journal: Blood Date: 2015-06-29 Impact factor: 22.113
Authors: Ching-Hon Pui; Jun J Yang; Stephen P Hunger; Rob Pieters; Martin Schrappe; Andrea Biondi; Ajay Vora; André Baruchel; Lewis B Silverman; Kjeld Schmiegelow; Gabriele Escherich; Keizo Horibe; Yves C M Benoit; Shai Izraeli; Allen Eng Juh Yeoh; Der-Cherng Liang; James R Downing; William E Evans; Mary V Relling; Charles G Mullighan Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544
Authors: Rachel E Rau; Yunfeng Dai; Meenakshi Devidas; Karen R Rabin; Patrick Zweidler-McKay; Anne Angiolillo; Reuven J Schore; Michael J Burke; Wanda L Salzer; Nyla A Heerema; Andrew J Carroll; Naomi J Winick; Stephen P Hunger; Elizabeth A Raetz; Mignon L Loh; Brent L Wood; Michael J Borowitz Journal: Pediatr Blood Cancer Date: 2021-02-09 Impact factor: 3.167