Xin-Yu Li1,2, Jia-Qiang Li1,2, Xue-Qun Luo3, Xue-Dong Wu4, Xin Sun5, Hong-Gui Xu1,2, Chang-Gang Li6, Ri-Yang Liu7, Xiao-Fei Sun8, Hui-Qin Chen9, Yu-Deng Lin10, Chi-Kong Li11, Jian-Pei Fang12,13. 1. Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. 3. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 4. Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 5. Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China. 6. Shenzhen Children's Hospital, Shenzhen, 518038, China. 7. Huizhou Municipal Central People's Hospital, Huizhou, 516001, China. 8. Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. 9. The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China. 10. Guangdong General Hospital, Guangzhou, 510080, China. 11. Hong Kong Children Hospital and Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 999077, China. 12. Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. fangjpei@mail.sysu.edu.cn. 13. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. fangjpei@mail.sysu.edu.cn.
Abstract
BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. METHODS: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. RESULTS: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). CONCLUSIONS: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. METHODS: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SRpatients received one CAM, others got two CAMs. RESULTS: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). CONCLUSIONS: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
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: Cornelis M van Tilburg; Elisabeth A M Sanders; Elisabeth E Nibbelke; Rob Pieters; Tom Revesz; Paul Westers; Tom F W Wolfs; Marc B Bierings Journal: Br J Haematol Date: 2011-01-11 Impact factor: 6.998
Authors: A Möricke; M Zimmermann; A Reiter; G Henze; A Schrauder; H Gadner; W D Ludwig; J Ritter; J Harbott; G Mann; T Klingebiel; F Zintl; C Niemeyer; B Kremens; F Niggli; D Niethammer; K Welte; M Stanulla; E Odenwald; H Riehm; M Schrappe Journal: Leukemia Date: 2009-12-10 Impact factor: 11.528
Authors: Lynda M Vrooman; Kristen E Stevenson; Jeffrey G Supko; Jane O'Brien; Suzanne E Dahlberg; Barbara L Asselin; Uma H Athale; Luis A Clavell; Kara M Kelly; Jeffery L Kutok; Caroline Laverdière; Steven E Lipshultz; Bruno Michon; Marshall Schorin; Mary V Relling; Harvey J Cohen; Donna S Neuberg; Stephen E Sallan; Lewis B Silverman Journal: J Clin Oncol Date: 2013-01-28 Impact factor: 44.544
Authors: Ching-Hon Pui; Dario Campana; Deqing Pei; W Paul Bowman; John T Sandlund; Sue C Kaste; Raul C Ribeiro; Jeffrey E Rubnitz; Susana C Raimondi; Mihaela Onciu; Elaine Coustan-Smith; Larry E Kun; Sima Jeha; Cheng Cheng; Scott C Howard; Vickey Simmons; Amy Bayles; Monika L Metzger; James M Boyett; Wing Leung; Rupert Handgretinger; James R Downing; William E Evans; Mary V Relling Journal: N Engl J Med Date: 2009-06-25 Impact factor: 91.245