Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial
Li Zhang,
Yao Zou,
Yumei Chen,
Ye Guo,
Wenyu Yang,
Xiaojuan Chen,
Shuchun Wang,
Xiaoming Liu,
Min Ruan,
Jiayuan Zhang,
Tianfeng Liu,
Fang Liu,
Benquan Qi,
Wenbin An,
Yuanyuan Ren,
Lixian Chang,
Xiaofan Zhu
Affiliations
Li Zhang
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yao Zou
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yumei Chen
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Ye Guo
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Wenyu Yang
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaojuan Chen
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Shuchun Wang
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaoming Liu
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Min Ruan
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Jiayuan Zhang
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tianfeng Liu
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Fang Liu
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Benquan Qi
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Wenbin An
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yuanyuan Ren
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Lixian Chang
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaofan Zhu
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Abstract Background The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. Methods We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016. All of the patients were assigned to receive ATRA plus ATO for induction followed by one course of idarubicin (IDA) and ATO (28 days). The patients were then randomly assigned to receive two courses of daunorubicin (DNR, no- Ara-C group) or DNR + Ara-C (Ara-C group). All of the patients were followed with maintenance therapy with oral ATRA, 6-mercaptopurine, and methotrexate for 1.5 years. Results Among the 66 patients, 43 were male and 23 were female. All of the patients achieved complete remission (CR) with the exception of one who gave up the treatment. During induction therapy, all toxicity events were reversed after appropriate management. Thirty patients in the Ara-C group underwent 57 courses of treatment, and 35 patients in the no-Ara-C group underwent 73 courses of treatment. No significant differences in age, genders, white blood cell counts, haemoglobin levels, and platelet counts were found between the Ara-C and no-Ara-c groups. Greater myelosuppression and sepsis were observed in the Ara-C group during the consolidation courses. No patient died at consolidation, and only one patient relapsed. No differences were found in event-free survival, disease-free survival and overall survival between the two groups. Additionally, our analysis of the arsenic levels in the plasma, urine, hair and nails of the patients indicated that no significant accumulation of arsenic occurred after ATO was discontinued for 12 months. Conclusions Overall, ATO and ATRA are safe and effective for paediatric APL patients and Ara-C could be omitted when ATO is used for two courses. Trial registration ClinicalTrials.gov (NCT01191541, retrospectively registered on 18 August 2010).
