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Quizartinib with donor lymphocyte infusion for post-transplant relapse of FLT3-ITD-positive acute myeloid leukemia

  • Fumihiko Ouchi,
  • Naoki Shingai,
  • Yuho Najima,
  • Daichi Sadato,
  • Chizuko Hirama,
  • Satoshi Wakita,
  • Kaori Kondo,
  • Yasutaka Sadaga,
  • Chika Kato,
  • Satoshi Sakai,
  • Yasuhiro Kambara,
  • Masashi Shimabukuro,
  • Kazuki Inai,
  • Takashi Toya,
  • Hiroaki Shimizu,
  • Kyoko Haraguchi,
  • Takeshi Kobayashi,
  • Hironori Harada,
  • Yoshiki Okuyama,
  • Hiroki Yamaguchi,
  • Yuka Harada,
  • Noriko Doki

摘要

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.