Case Presentation
An 87-year-old male presented with leukoblastosis in December 2017. He was being treated for heart failure and had undergone percutaneous coronary intervention for proximal, middle, and distal branches of right coronary artery and a circumflex branch of left coronary artery(#1–3 and #12–14). Additionally, he had type 2 diabetes mellitus (DM) and chronic kidney disease. Physical examination showed no particular abnormalities. The laboratory findings were as follows: white blood cell count, 9.9 × 109/L with 21.5% blast cells; hemoglobin, 12.5 g/dL; platelet count, 20.9 × 109/L; and lactate dehydrogenase, 556 IU/L. Bone marrow examination showed hypocellularity with 41.4% medium- and large-sized blasts, which were negative for myeloperoxidase staining by immunohistochemical analysis (Figure 1). Flow cytometric analysis showed that the blast cells were strongly positive for CD10 (87.9%), CD19 (59.8%), CD33 (84.5%), CD34 (94.1%), HLA-DR (98.4%), cytoplasmic CD79a (76.1%), TdT (92.2%), and KORSA (65.1%) and weakly positive for myeloperoxidase (30.7%) (Figure 2). Chromosomal analysis of the bone marrow cells revealed 46, XY,t(9;22)(q34;q11.2) in 17 out of a total of 20 cells in metaphase. The minor BCR-ABL1 mRNA level in the bone marrow was 460 000 copies/µg RNA. Additional examination did not reveal splenomegaly, history of CML, or increases in peripheral white blood cell or absolute basophil count. Based on these results, the patient was diagnosed with Ph+ MPAL according to the 2016 WHO classification.
He was started on 60 mg (40 mg/m2) prednisolone as pretherapy from January 2018. Based on the medical history including type 2 DM and cardiovascular comorbidity, he was initiated on 50 mg/kg dasatinib one week after the initiation of prednisolone. However, dasatinib was discontinued after the patient exhibited grade 2 QT prolongation and interstitial pneumonitis ten days after the initiation of dasatinib (Figure 3). After the improvement of his respiratory status, dasatinib was replaced with imatinib (300 mg/day) in February 2018. However, the imatinib dose was reduced to 150–200 mg/day after the development of grade 2 acute renal failure and QT prolongation. Although temporary interruption was necessary to address renal failure and infectious pneumonia, the patient continued treatment with imatinib (150–200 mg/day). Hematological complete remission (CR) was achieved 40 days after the imatinib initiation. Six months after imatinib starting, the blood concentration of imatinib was 1,308 ng/mL (>1,000 ng/mL), and hematological CR was maintained. Drug concentration monitoring of imatinib was continued for one year (Figure 4), and the minor BCR-ABL1 mRNA level in bone marrow declined from 460 000 to 58 copies/µg RNA in January 2019. Hematological CR was maintained for over a year without the interruption of imatinib by monitoring of blood imatinib concentrations (Figure 5).