骨髓增生异常肿瘤伴单纯5q-进展为肥大细胞白血病-骨髓增生异常肿瘤1例临床分析并文献复习

Clinical analysis of a case with 5q-myelodysplastic neoplasms progressed to mast cell leukemia-myelodysplastic neoplasm and literature review

目的探讨骨髓增生异常肿瘤(MDS)伴单纯5q-进展为肥大细胞白血病(MCL)-MDS患者的临床特征及诊治,并进行相关文献复习。方法选择2021年4月6日广元市中心医院血液科收治的1例MDS伴单纯5q-进展为MCL-MDS的66岁男性患者为研究对象。采用回顾性分析方法,对本例患者的病史、临床特征、实验室及辅助检查结果等临床资料进行分析。根据患者临床表现、实验室及辅助检查结果,对其进行诊断和治疗。对本例患者的随访截至2022年12月9日。本研究以"骨髓增生异常综合征""骨髓增生异常肿瘤""肥大细胞白血病""原癌基因蛋白质类c-kit""5q-""ASXL1""myelodysplastic syndromes""myelodysplastic neoplasm""mast-cell leukemia""proto-oncogene proteins c-kit"为中、英文关键词,在中国知网数据库、万方数据服务知识平台及PubMed数据库中检索MCL-MDS患者相关文献,并对文献报道的MCL-MDS患者进行分析和总结。文献检索时间为2001年1月1日至2022年12月8日。本研究获得广元市中心医院伦理委员会审批(批准文号:GYZXLL202379),并与患者签署临床研究知情同意书。结果①本例患者因"气促、乏力5个月,加重1+个月"入院。院外就诊时发现血红蛋白(Hb)值显著降低,予悬浮红细胞输注后症状好转,但是气促、乏力症状反复。②入院后本例患者血常规检查结果示,大细胞性贫血,Hb值为41 g/L,平均红细胞体积(MCV)为119.7 fL。腹部彩色多普勒超声检查结果示,轻度脾大。骨髓细胞形态学检查和骨髓病理活组织检查结果示,红系、粒系、巨核系均存在病态造血。核型分析结果显示5q-。MDS全基因组芯片检测结果显示,5q-嵌合。二代测序结果示,存在ASXL1、KIT突变。③本例患者被诊断为MDS伴单纯5q-、KIT及ASXL1突变。予地西他滨(10 mg/d×7 d,6周为1个疗程)+来那度胺(10 mg/d×21 d,4周为1个疗程)治疗7个疗程后,患者病情好转,脱离输血依赖,Hb值维持为88~90 g/L。2022年1月起继续接受来那度胺单药治疗(25 mg/d),并定期复查,Hb值为80~90 g/L,无其他血细胞减少症状。13个月后患者出现皮疹、乏力、腹痛。再次行腹部彩色多普勒超声检查结果示,脾体积明显增大(长径为18 cm)。复查骨髓涂片细胞学、骨髓细胞流式细胞术(FCM)免疫分型及骨髓活组织检查发现异常肥大细胞。依据患者临床表现及相关检查结果,本例患者被诊断为MCL-MDS,予达沙替尼(100 mg/d)联合DA3+7(柔红霉素40 mg/d,d1~3+阿糖胞苷100 mg/d,d1~7)方案治疗。治疗后患者脾体积缩小,输血间隔时间延长。复查骨髓细胞形态学检查结果示,肥大细胞比例为8.5%。患者出院后因不能耐受胃肠道不良反应自行停用达沙替尼。截至随访结束,患者仍存活。④按照本研究设定的文献检索策略,纳入2篇MCL-MDS相关文献。共计纳入包括本研究1例患者在内的3例由MDS进展为MCL-MDS病例。其中,1例患者未行KIT突变检测,伴t(9;22)及20q-,予泼尼松50 mg/d治疗,生存期为2个月。另1例患者不伴KIT D816V,染色体核型正常,予伊马替尼100 mg/d治疗,生存期为3个月。本研究患者伴5q-、ASXL1及KIT突变,予达沙替尼100 mg/d联合DA3+7方案,生存期>5个月。结论本例患者为MDS进展为MCL-MDS,考虑与伴KIT及ASXL1突变相关。MCL-MDS患者预后非常差,单用糖皮质激素、酪氨酸激酶抑制剂(TKI)疗效欠佳,TKI联合化疗可能延长患者生存期。

ObjectiveTo investigate clinical characteristics,diagnosis and treatment of myelodysplastic neoplasms(MDS)with simple 5q-progressed to mast cell leukemia(MCL)-MDS,and to review related literature.MethodsOn April 6,2021,a case of 66 year-old male patient of MDS with simple 5q-progressed to MCL-MDS who was admitted to Department of Hematology,Guangyuan Central Hospital was selected as the study subject.Clinical data such as medical history,clinical features,laboratory and auxiliary examination results were retrospectively analyzed.This patient was diagnosed and treated according to the clinical manifestations,laboratory and auxiliary examination results.This patient was followed up until December 9,2022.With"myelodysplastic syndrome""myelodysplastic neoplasm""mast cell leukemia""proto-oncogene proteins c-kit""5q-""ASXL1"as Chinese and English keywords,literature related to MCL-MDS patients was searched in China National Knowledge Infrastructure database,Wanfang Data knowledge service platform and PubMed database,and literature reports of MCL-MDS patients were summarized and analyzed.The period of literature search was from January 1,2001 to December 8,2022.This study was approved by the Ethic Committee of Guangyuan Central Hospital(Approval No.GYZXLL202379)and the informed consent for clinical study was signed with the patient.Results①This patient was admitted to hospital due to"shortness of breath and weakness for 5 months,aggravated for more than a month".Hemoglobin(Hb)value was significantly reduced outside the hospital,and the symptoms improved after transfusion of suspended red blood cells,but the symptoms of shortness of breath and fatigue were recurred.②After admission,this patient′s blood routine examination results showed large cell anemia,and Hb value was 41 g/L,mean corpuscular volume(MCV)was 119.7 fl.Abdominal color Doppler ultrasound results showed mild splenomegaly.Results of bone marrow cytology and pathological biopsy showed that the erythrocyte,granulocyte and megakaryocyte all had pathological hematopoiesis.Karyotype analysis results showed 5q-.MDS whole genome chip detection results showed that 5q-chimerism.The next generation sequencing results showed ASXL1 and KIT mutations.③This patient was diagnosed as MDS with simple 5q-,ASXL1 and KIT mutations.After 7 courses of combined treatment with decitabine(10 mg/d×7 d,6 weeks as 1 treatment course)and lenalidomide(10 mg/d×21 d,4 weeks as 1 treatment course),this patient′s condition improved,he was free from blood transfusion dependence,and Hb values were maintained at 88-90 g/L.From January 2022,lenalidomide monotherapy(25 mg/d)was continued and regular review was performed,with Hb values of 80-90 g/L and no other symptoms of hemocytopenia.Thirteen months later,this patient developed rash,fatigue,and abdominal pain.Color Doppler ultrasound examination of the abdomen again showed significant enlargement of the spleen(length diameter 18 cm).Bone marrow cytology,bone marrow flow cytometry(FCM),and bone marrow biopsy showed abnormal mast cells.According to clinical manifestation and related examination results,this patient was diagnosed as MCL-MDS.Dasatinib(100 mg/d)combined with DA3+7(daunorubicin 40 mg/d,d1-3+cytarabine 100 mg/d,d1-7)regimen was administered.After treatment,the patient′s spleen volume was reduced and the interval between transfusion was prolonged.Reexamination of bone marrow cell morphology showed that the proportion of mast cells was 8.5%.After discharge,the patient stopped using dasatinib on his own due to gastrointestinal adverse reactions,and the patient was still alive until the end of follow-up.④According to the literature search strategy established in this study,2 articles related to MCL-MDS were included.A total of 3 cases of MDS progressed to MCL-MDS were included,including 1 case in this study.Among them,1 patient did not undergo KIT mutation detection and was accompanied by t(9;22)and 20q-were treated with prednisone 50 mg/d,and the survival time was 2 months.Another patient was negative for KIT D816V and normal karyotype,and was treated with imatinib 100 mg/d,and the survival time was 3 months.In this study,the patient was positive for KIT and ASXL1 mutations,accompanied by 5q-,and was given dasatinib 100 mg/d combined with DA3+7 regimen.the survival time was more than 5 months.ConclusionsIn this case,MDS progressed to MCL-MDS,which was considered to be related to KIT and ASXL1 mutations.The prognosis of MCL-MDS patients is very poor.Glucocorticoids and tyrosine kinase inhibitor(TKI)alone are not effective,and TKI combined with chemotherapy may prolong the survival time of patients.