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Drug resistance: case report A man in his early 20s developed drug resistance during treatment with nilotinib and ponatinib for chronic-phase chronic myeloid leukaemia (CML) [routes not stated]. The man (at the age of 20 years) was diagnosed with chronic phase-CML in June 2012. At presentation, he had hyperleucocytosis, and cytogenetic analysis showed karyotype 46, XY,t (9;22) (q34;q11) mutation. His BCR-ABL1-p210 transcript ratio in bone marrow was 102.588%. In June 2012, he started receiving treatment with nilotinib 150mg twice daily, which was further increased to 300mg twice daily. Three months after the initiation of nilotinib (in October 2012), complete haematological remission was achieved, and his BCR-ABL1-p210 transcript ratio decreased to 1.046%. In September 2013, he exhibited treatment failure with an increase in the BCR-ABL1-p210 transcript ratio. There were no signs of a lack of treatment adherence, but ABL1 mutations associated with nilotinib resistance were found. Hence, the man’s treatment with nilotinib was changed to ponatinib 30mg once daily in September 2013. However, further increased BCR-ABL1-p210 transcript ratio was observed. Cytogenetic analysis of bone marrow revealed complete cytogenetic response loss. Afterwards, blast-phase CML with hyperleucocytosis was developed with 75% myeloid blasts in the peripheral blood. Repeat cytogenetic analysis confirmed the co-occurrence of the CBFB-MYH11 and the BCR-ABL1 gene in the same metaphase, which was pre-existed in the chronic phase clone. At the blast phase, the extensive mutational analysis revealed 3 different in-frame indel mutations in KIT exon 8, which were acquired under treatment with nilotinib and ponatinib and caused treatment resistance. Therefore, induction chemotherapy with cytarabine and daunorubicin was initiated in February 2014, followed by dasatinib in March 2014. He also underwent haematopoietic stem cell transplantation in March 2014. At follow-up in December 2019 (90 months after the initial diagnosis), he had complete remission of the disease. Shoumariyeh K, et al. Blastic transformation of BCR-ABL1 positive chronic myeloid leukaemia through acquisition of CBFB-MYH11 and mutant KIT. British Journal of 803506647 Haematology 190: e339-e343, No. 6, Sep 2020. Available from: URL: http://doi.org/10.1111/bjh.16904

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Reactions 17 Oct 2020 No. 1826