Rob Pieters1, Hester de Groot-Kruseman2, Vincent Van der Velden2, Marta Fiocco2, Henk van den Berg2, Evelien de Bont2, R Maarten Egeler2, Peter Hoogerbrugge2, Gertjan Kaspers2, Ellen Van der Schoot2, Valerie De Haas2, Jacques Van Dongen2. 1. Rob Pieters, Peter Hoogerbrugge, and Gertjan Kaspers, Princess Máxima Center for Pediatric Oncology, Utrecht; Rob Pieters, Hester de Groot-Kruseman, Marta Fiocco, and Valerie De Haas, Dutch Childhood Oncology Group, The Hague; Vincent Van der Velden and Jacques Van Dongen, University Medical Center Rotterdam, Rotterdam; Marta Fiocco, Leiden University, Leiden; Henk van den Berg, Academic Medical Center; Gertjan Kaspers, Free University Hospital Amsterdam; Ellen Van der Schoot, Sanquin Research, Amsterdam; Evelien de Bont, University of Groningen, Groningen, the Netherlands; and R. Maarten Egeler, The Hospital for Sick Children, Toronto, Canada. r.pieters@prinsesmaximacentrum.nl. 2. Rob Pieters, Peter Hoogerbrugge, and Gertjan Kaspers, Princess Máxima Center for Pediatric Oncology, Utrecht; Rob Pieters, Hester de Groot-Kruseman, Marta Fiocco, and Valerie De Haas, Dutch Childhood Oncology Group, The Hague; Vincent Van der Velden and Jacques Van Dongen, University Medical Center Rotterdam, Rotterdam; Marta Fiocco, Leiden University, Leiden; Henk van den Berg, Academic Medical Center; Gertjan Kaspers, Free University Hospital Amsterdam; Ellen Van der Schoot, Sanquin Research, Amsterdam; Evelien de Bont, University of Groningen, Groningen, the Netherlands; and R. Maarten Egeler, The Hospital for Sick Children, Toronto, Canada.
Abstract
PURPOSE: Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification. METHODS: Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls. RESULTS: In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols. CONCLUSION: Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification.
PURPOSE: Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification. METHODS:Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls. RESULTS: In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols. CONCLUSION: Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification.
Authors: Franziska Schramm; Udo Zur Stadt; Martin Zimmermann; Norbert Jorch; Arnulf Pekrun; Arndt Borkhardt; Thomas Imschweiler; Holger Christiansen; Jörg Faber; Irene Schmid; Tobias Feuchtinger; Gerhard Beron; Monique L den Boer; Rob Pieters; Martin A Horstmann; Gritta E Janka-Schaub; Gabriele Escherich Journal: Blood Adv Date: 2019-11-26
Authors: Ao-Li Zhang; Xiao-Juan Chen; Yao Zou; Wen-Yu Yang; Ye Guo; Shu-Chun Wang; Li Zhang; Xiao-Ming Liu; Min Ruan; Tian-Feng Liu; Ben-Quan Qi; Xiao-Fan Zhu Journal: Zhongguo Dang Dai Er Ke Za Zhi Date: 2019-08
Authors: Erica Brivio; Franco Locatelli; Marta Lopez-Yurda; Andrea Malone; Cristina Díaz-de-Heredia; Bella Bielorai; Claudia Rossig; Vincent H J van der Velden; Anneke C J Ammerlaan; Adriana Thano; Inge M van der Sluis; Monique L den Boer; Ying Chen; Barbara Sleight; Benoit Brethon; Karsten Nysom; Lucie Sramkova; Ingrid Øra; Luciana Vinti; Christiane Chen-Santel; Christian Michel Zwaan Journal: Blood Date: 2021-03-25 Impact factor: 22.113