伊马替尼治疗胃肠间质瘤后继发急性早幼粒细胞白血病

Acute Promyelocytic Leukemia Developed during Imatinib Therapy for Gastrointestinal Stromal Tumors

目的:探讨伊马替尼治疗胃肠间质瘤(gastrointestinal stromal tumor,GIST)后继发急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)的临床特点和诊断治疗。方法:患者在手术确诊GIST后接受伊马替尼治疗,1年后继发APL。结合文献复习,探讨两种疾病间的关系及治疗和预后。结果:胃肿块行腹腔镜切除,组织病理学和免疫组织化学检查确诊为GIST,中度恶性。于术后予以伊马替尼400 mg/天治疗,1年后出现全血细胞减少,骨髓细胞学检查发现增生极度活跃,异常早幼粒细胞占92.5%。流式细胞免疫分型显示,异常细胞表达CD117、CD33、CD38和cMPO,不表达HLA-DR和CD34。染色体核型46,XX,t(15;17)(q22;q21),PML/RARα融合基因阳性,确诊为APL;经全反式维A酸、三氧化二砷和去甲氧柔红霉素联合治疗后获完全缓解。结论:GIST可与APL或其它血液肿瘤同时或异时性发生,两者在发病机理上可能存在联系。

Objective： To investigate the clinicopathologic and molecular characteristics of acute promyelocytic leukemia（APL） developed during imatinib therapy for gastrointestinal stromal tumors（GIST）. Methods： A 49-year-old woman was hospitalized for abdominal pain. The abdominal CT revealed a gastric mass. Laparoscopic resection of the tumor was performed. The histopathologic analysis showed poorly differentiated malignant cell infiltration with epithelioid features. Immunohistochemistry staining of these cells was positive for CDll7 and CD34. GIST was confirmed and imatinib treatment was given. Results： After 1 year, the patient developed progressive pancytopenia. Bone marrow aspirate showed marked hyperplasia of bone marrow cells with 92.5% promyelocyte, consistent with APL. Cytogenetic analysis demonstrated t（ 15;17 ） （q22;q21） as the sole abnormality. PML/RARα fusion gene was positive and Kit mutation was negative. After combined treatment with ATRA, arsenic trioxide and idarubicin, patient achieved cytogenetic and molecular remission. Conclusion ： The metachronous coexistence of GIST with APL is uncommon. The potential nonrandom association and causal relationship between these malignancies remained to be investigated. Further studies would be necessary to clarify the relationship between imatinib and secondary malignancies in GIST patients.