Ouchi Fumihiko, Shingai Naoki, Najima Yuho, Sadato Daichi, Hirama Chizuko, Wakita Satoshi, Kondo Kaori, Sadaga Yasutaka, Kato Chika, Sakai Satoshi, Kambara Yasuhiro, Shimabukuro Masashi, Inai Kazuki, Toya Takashi, Shimizu Hiroaki, Haraguchi Kyoko, Kobayashi Takeshi, Harada Hironori, Okuyama Yoshiki, Yamaguchi Hiroki, Harada Yuka, Doki Noriko
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-8-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan.
Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Int J Hematol. 2025 Jan;121(1):137-143. doi: 10.1007/s12185-024-03863-4. Epub 2024 Oct 26.
FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia (AML) has a poor prognosis, particularly with DNMT3A and NPM1 mutations. Quizartinib, a FLT3 inhibitor showing clinical benefit in FLT3-ITD-positive AML, has unclear safety and efficacy when combined with donor lymphocyte infusion (DLI). We report a case of FLT3-ITD-positive AML with DNMT3A and NPM1 mutations that relapsed after allogeneic hematopoietic stem cell transplantation (allo-HCT) and was treated with quizartinib and DLI. A 49-year-old man was diagnosed with AML. Target-sequencing analysis of the bone marrow revealed FLT3-ITD, DNMT3A R882, and NPM1 mutations. Although the patient achieved complete remission (CR) through induction therapy and received allo-HCT, he relapsed on day 71. Quizartinib was initiated on day 79, and the patient achieved CR with incomplete recovery on day 106. He did not desire a second allo-HCT and continued quizartinib in combination with DLI, which was started on day 156 and administered eight times every 2 to 3 months. The patient achieved hematological CR on day 163 and remained in molecular CR 3 years after allo-HCT without adverse effects. Quizartinib combined with DLI may be a feasible treatment for early relapse of FLT3-ITD-positive AML after allo-HCT, even with concurrent DNMT3A and NPM1 mutations.
FMS样酪氨酸激酶3内部串联重复（FLT3-ITD）阳性的急性髓系白血病（AML）预后较差，尤其是伴有DNMT3A和NPM1突变时。Quizartinib是一种在FLT3-ITD阳性AML中显示出临床益处的FLT3抑制剂，与供体淋巴细胞输注（DLI）联合使用时，其安全性和疗效尚不清楚。我们报告了1例伴有DNMT3A和NPM1突变的FLT3-ITD阳性AML病例，该患者在异基因造血干细胞移植（allo-HCT）后复发，并接受了Quizartinib和DLI治疗。一名49岁男性被诊断为AML。骨髓靶向测序分析显示存在FLT3-ITD、DNMT3A R882和NPM1突变。尽管患者通过诱导治疗实现了完全缓解（CR）并接受了allo-HCT，但在第71天复发。在第79天开始使用Quizartinib，患者在第106天实现了CR但恢复不完全。他不希望进行第二次allo-HCT，继续使用Quizartinib联合DLI，DLI于第156天开始，每2至3个月给药8次。患者在第163天实现了血液学CR，allo-HCT后3年仍处于分子CR状态，且无不良反应。Quizartinib联合DLI可能是allo-HCT后FLT3-ITD阳性AML早期复发的一种可行治疗方法，即使同时存在DNMT3A和NPM1突变。
