Aoyama Kazutoshi, Yamasaki Yoshitaka, Mouri Fumihiko, Maehiro Yoshimi, Takaki Yusuke, Oya Shuki, Nakamura Takayuki, Morishige Satoshi, Yamaguchi Maki, Nagafuji Koji
Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine.
Rinsho Ketsueki. 2022;63(7):764-769. doi: 10.11406/rinketsu.63.764.
FMS-like tyrosine kinase 3 (FLT3) inhibitors improve the prognosis of FLT3-internal tandem duplication (ITD)-positive acute myeloid leukemia (AML). Case 1 is a 47-year-old male patient who presented with a white blood cell count (WBC) of 95,700/ml with 94% blast accompanied by cuplike nuclei, lactate dehydrogenase (LDH) of 2,434 IU/l, fibrin degradation products (FDP) of 476 mg/ml, and a bone marrow examination that revealed blastic marrow with chromosome 46, XY, positive FLT3-ITD, and positive nucleophosmin 1 (NPM1) mutation type A. Flow cytometry revealed that blasts were positive for CD33 and negative for CD34, CD117, and human leukocyte antigen-DR isotype (HLA-DR). The patient had no response to idarubicin combined cytarabine; however, qiuzartinib administration resulted in the first complete remission. Case 2 is a 71-year-old female patient, who presented with 94,900/ml of WBC with a 91% blast accompanied with cup-like nuclei, LDH of 19,03 IU/l, FDP of 112 mg/ml, and a peripheral blood examination that revealed chromosome 46, XX, positive FLT3-ITD, and positive NPM1 mutation type B. Flow cytometry revealed that blasts were positive for CD33 and negative for CD34, CD117, and HLA-DR. She had a partial response to venetoclax combined with azacytidine, and qiuzartinib administration resulted in the first complete remission. Both cases were CD34- and HLA-DR-negative with disseminated intravascular coagulation mimicking acute promyelocytic leukemia (APL). Additionally, recognizing the cuplike blasts is useful to differentiate FLT3 mutant AML from APL for the proper use of FLT3 inhibitors.
FMS样酪氨酸激酶3（FLT3）抑制剂可改善FLT3内部串联重复（ITD）阳性急性髓系白血病（AML）的预后。病例1是一名47岁男性患者，白细胞计数（WBC）为95,700/ml，原始细胞占94%，伴有杯状核，乳酸脱氢酶（LDH）为2,434 IU/l，纤维蛋白降解产物（FDP）为476 mg/ml，骨髓检查显示骨髓原始细胞增多，染色体为46, XY，FLT3-ITD阳性，核磷蛋白1（NPM1）突变A型阳性。流式细胞术显示原始细胞CD33阳性，CD34、CD117和人类白细胞抗原-DR同种型（HLA-DR）阴性。该患者对伊达比星联合阿糖胞苷无反应；然而，使用quizartinib后实现了首次完全缓解。病例2是一名71岁女性患者，白细胞计数为94,900/ml，原始细胞占91%，伴有杯状核，LDH为19,03 IU/l，FDP为112 mg/ml，外周血检查显示染色体为46, XX，FLT3-ITD阳性，NPM1突变B型阳性。流式细胞术显示原始细胞CD33阳性，CD34、CD117和HLA-DR阴性。她对维奈克拉联合阿扎胞苷有部分反应，使用quizartinib后实现了首次完全缓解。两例患者均为CD34和HLA-DR阴性，伴有模拟急性早幼粒细胞白血病（APL）的弥散性血管内凝血。此外，识别杯状原始细胞有助于将FLT3突变型AML与APL区分开来，以便正确使用FLT3抑制剂。
