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Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study |
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| Authors: | Honghong Zhang MD Yang Wan MD PhD Hongsheng Wang MD Jiaoyang Cai MD PhD Jie Yu MD Shaoyan Hu MD PhD Yongjun Fang MD PhD Ju Gao MD PhD Hua Jiang MD PhD Minghua Yang MD PhD Changda Liang MD Runming Jin MD PhD Xin Tian MD PhD Xiuli Ju MD PhD Qun Hu MD PhD Hui Jiang MD Zhifan Li MD PhD Ningling Wang MD Lirong Sun MD PhD Alex W. K. Leung MBChB Xuedong Wu MD PhD Xiaowen Qian MD Maoxiang Qian PhD Chi-kong Li MBBS MD Jun Yang PhD Jingyan Tang MD PhD Xiaofan Zhu MD PhD Shuhong Shen MD PhD Li Zhang MD PhD Ching-Hon Pui MD Xiaowen Zhai MD PhD |
| Affiliation: | 1. Department of Hematology/Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China;2. Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China;3. Department of Hematology/Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China;4. Department of Hematology/Oncology, Chongqing Medical University Affiliated Children's Hospital, Chongqing, China;5. Department of Hematology/Oncology, Children's Hospital of Soochow University, Suzhou, China;6. Department of Hematology/Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China;7. Department of Pediatrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Disease of Women and Children, Ministry of Education, Chengdu, China;8. Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou, China;9. Department of Pediatrics, Xiangya Hospital Central South University, Changsha, China;10. Department of Hematology/Oncology, Jiangxi Provincial Children's Hospital, Nanchang, China;11. Department of Pediatrics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;12. Department of Hematology/Oncology, KunMing Children's Hospital, Kunming, China;13. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China;14. Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;15. Department of Hematology/Oncology, Children's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China;16. Department of Hematology/Oncology, Xi'an Northwest Women's and Children's Hospital, Xi'an, China;17. Department of Pediatrics, Anhui Medical University Second Affiliated Hospital, Hefei, Anhui, China;18. Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, China;19. Department of Pediatrics, Hong Kong Children's Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;20. Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China;21. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA;22. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA |
| Abstract: | BackgroundContemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome.MethodsThe authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation.ResultsThe overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6–88.3) and 5-year overall survival 88.9% (95% CI, 85.5–92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8–86.4] vs. 88.9%, [95% CI, 84.1–93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2–87.4] vs. 87.1%, [95% CI, 83.4–90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6–96.1] vs. 83.0% [95% CI, 77.5–88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2–14.5], p < .001).ConclusionsThese data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL. |
| Keywords: | acute lymphoblastic leukemia event-free survival prognostic factor TCF3::PBX1 |