Whole-exome sequencing identifies FANC heterozygous germline mutation as an adverse factor for immunosuppressive therapy in Chinese aplastic anemia patients aged 40 or younger: a single-center retrospective study
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Published:2023-01-09
Issue:3
Volume:102
Page:503-517
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ISSN:0939-5555
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Container-title:Annals of Hematology
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language:en
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Short-container-title:Ann Hematol
Author:
Shen Yingying, Liu Qi, Li Hangchao, Liu Wenbin, Hu Huijin, Zhao Yuechao, Li Yuzhu, Chen Ying, Liu Shan, Yu Qinghong, Zhuang Haifeng, Wu Liqiang, Hu Zhiping, Zheng Zhiyin, Shen Jianping, Lin Shenyun, Shen Yiping, Zhou Yuhong, Ye Baodong, Wu DijiongORCID
Abstract
AbstractAcquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell–transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).
Funder
National Natural Science Foundation of China Zhejiang Scientific Research Fund of Traditional Chinese Medicine Health technology Plan of Zhejiang Province
Publisher
Springer Science and Business Media LLC
Subject
Hematology,General Medicine
Reference38 articles.
1. Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108(8):2509–2519. https://doi.org/10.1182/blood-2006-03-010777 2. Georges GE, Doney K, Storb R (2018) Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment. Blood Adv 2(15):2020–2028. https://doi.org/10.1182/bloodadvances.2018021162 3. Zhu XF, He HL, Wang SQ, Tang JY, Han B, Zhang DH, Wu LQ, Wu DP, Li W, Xia LH, Zhu HL, Liu F, Shi HX, Zhang X, Zhou F, Hu JD, Fang JP, Chen XQ, Ye TZ et al (2019) Current treatment patterns of aplastic anemia in China: a prospective cohort registry study. Acta Haematol 142(3):162–170. https://doi.org/10.1159/000499065 4. Bacigalupo A, Oneto R, Schrezenmeier H, Hochsmann B, Dufour C, Kojima S, Zhu X, Chen X, Issaragrisil S, Chuncharunee S, Jeong DC, Giammarco S, Van Lint MT, Zheng Y, Vallejo C (2018) First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: outcome of 955 patients treated 2001-2012. Am J Hematol 93(5):643–648. https://doi.org/10.1002/ajh.25081 5. Jin JY, Kim DW, Lee JW, Han CW, Min WS, Park CW, Kim CC, Kim DJ, Kim HK, Song HH (1995) Immune suppression therapy in aplastic anemia: influencing factors on response and survival. Korean J Intern Med 10(1):25–31. https://doi.org/10.3904/kjim.1995.10.1.25
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