Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol
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 carr...
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doaj-598bd0c56f2e463e91357af329b8584c2021-01-17T12:57:05ZengBMCBMC Cancer1471-24072021-01-0121111110.1186/s12885-020-07752-xReduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocolXin-Yu Li0Jia-Qiang Li1Xue-Qun Luo2Xue-Dong Wu3Xin Sun4Hong-Gui Xu5Chang-Gang Li6Ri-Yang Liu7Xiao-Fei Sun8Hui-Qin Chen9Yu-Deng Lin10Chi-kong LI11Jian-Pei Fang12Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityThe First Affiliated Hospital, Sun Yat-sen UniversityNanfang Hospital, Southern Medical UniversityGuangzhou Women and Children’s Medical CenterDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityShenzhen Children’s HospitalHuizhou Municipal Central People’s HospitalSun Yat-sen University Cancer CenterThe Third Affiliated Hospital, Sun Yat-sen UniversityGuangdong General HospitalHong Kong Children Hospital and Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAbstract 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.https://doi.org/10.1186/s12885-020-07752-xAcute lymphoblastic leukemiaChildrenChemotherapyReduced intensity multi-centric clinical study |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin-Yu Li Jia-Qiang Li Xue-Qun Luo Xue-Dong Wu Xin Sun Hong-Gui Xu Chang-Gang Li Ri-Yang Liu Xiao-Fei Sun Hui-Qin Chen Yu-Deng Lin Chi-kong LI Jian-Pei Fang |
spellingShingle |
Xin-Yu Li Jia-Qiang Li Xue-Qun Luo Xue-Dong Wu Xin Sun Hong-Gui Xu Chang-Gang Li Ri-Yang Liu Xiao-Fei Sun Hui-Qin Chen Yu-Deng Lin Chi-kong LI Jian-Pei Fang Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol BMC Cancer Acute lymphoblastic leukemia Children Chemotherapy Reduced intensity multi-centric clinical study |
author_facet |
Xin-Yu Li Jia-Qiang Li Xue-Qun Luo Xue-Dong Wu Xin Sun Hong-Gui Xu Chang-Gang Li Ri-Yang Liu Xiao-Fei Sun Hui-Qin Chen Yu-Deng Lin Chi-kong LI Jian-Pei Fang |
author_sort |
Xin-Yu Li |
title |
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol |
title_short |
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol |
title_full |
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol |
title_fullStr |
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol |
title_full_unstemmed |
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol |
title_sort |
reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of gd-2008-all protocol |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2021-01-01 |
description |
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. |
topic |
Acute lymphoblastic leukemia Children Chemotherapy Reduced intensity multi-centric clinical study |
url |
https://doi.org/10.1186/s12885-020-07752-x |
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