Gilteritinib
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Drug resistance secondary to acquisition of BCR-ABL1 mutation: case report A 52-year-old woman exhibited drug resistance secondary to acquisition of BCR-ABL1 mutation following treatment with gilteritinib for acute myeloid leukaemia (AML) [route and dosage not stated]. In December 2018, the woman was diagnosed with AML with monocytic differentiation. Bone marrow aspirate smears demonstrated 84%blasts and flow cytometry immunophenotyping demonstrated aberrant myeloblasts positive for CD11b, CD13 (partial), CD33, CD34, CD38, CD64 (partial), CD117, HLADR and myeloperoxidase. Additionally, an abnormal/immature monocytic population positive for CD13, CD33, CD64. Conventional cytogenetic analysis demonstrated a diploid female karyotype: 46,XX [4]. She received induction chemotherapy with cytarabine, daunorubicin and midostaurin, followed by two additional cycles of cytarabine. Following this, she achieved remission for a short duration. However, in May 2019, she had a relapse. She then recommenced on induction therapy with mitoxantrone, etoposide and cytarabine [Ara-C] followed by monotherapy with gilteritinib. However, despite therapy, her disease progressed. FISH showed positive result for BCR-ABL1. She then referred to another hospital for AML. During genetic evaluation, the t(1;9;22)(q23;q34;q11.2) indicated a three-way translocation with BCR-ABL1. FISH was positive for BCR-ABL1 in 92.5% of interphases. Quantitative real time RT-PCR analysis demonstrated an e1a2 BCR-ABL1 fusion transcript coding for 190KDa BCR-ABL1 protein. The percentage of BCR-ABL1 to ABL1 transcripts was 63.8%. A 27-base pair insertion was detected in exon 14, consistent with the FLT3-ITD. As she had received intensive chemotherapy on two prior occasions, including the MEC regimen with gilteritinib without any response, she switched to a hypomethylating agent based therapy. She was continued on gilteritinib a potent FLT3 inhibitor. In addition to this, off-label ponatinib a multi-kinase inhibitor and decitabine, a hypomethylating agent was commenced. This led to a reduction in blast count to 8%. Regrettably, she died due to septic shock and multi-organ failure. Thakral B, et al. Clonal evolution with acquisition of BCR-ABL1 in refractory acute myeloid leukemia post therapy with FLT3-inhibitor. Leukemia and Lymphoma : 1-4, 22 803499003 Jul 2020. Available from: URL: http://doi.org/10.1080/10428194.2020.1797008
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Reactions 29 Aug 2020 No. 1819
