Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report

Abstract

A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir. Bone marrow (BM) aspiration and biopsy revealed hypercellular marrow filled with blasts. Sequencing of the leukemia cells revealed overlapping peaks for the wild-type sequence and the T315I mutant sequence. The patient was treated with 500 mg bosutinib (which was later reduced to 300 mg) for pretransplant cytoreduction. After 5 months, the patient's spleen exhibited a reduction in volume and the percentage of blasts in the BM decreased from 96.1 to 17.5%. The patient successfully underwent cord blood transplantation. The patient has been disease-free for 5 months subsequent to transplantation. This case suggests that bosutinib may be effective for cytoreduction prior to stem cell transplantation, unless the leukemia cells consistently harbor the T315I mutation.

Keywords: T315I mutation; blastic phase; bosutinib; chronic myeloid leukemia; tyrosine kinase inhibitor.

Figure 1.

May-Grünwald Giemsa staining of BM aspirate smears. (A) BM at the initial diagnosis of CML-CP. Black arrows illustrate the blasts. (B) BM at the diagnosis of CML-BP. Original magnification, ×400. BM, bone marrow; CML, chronic myeloid leukemia; CP, chronic phase; BP, blastic phase.

Figure 2.

Sequencing chromatograms of the BCR-ABL1 fusion gene, particularly the regions flanking amino acid T315 of ABL1. (A) Sequencing chromatogram that was obtained prior to bosutinib administration. The central codon, ACT, corresponds to wild-type T315. The overlapping peaks of wild-type and C >T (T315I) mutation ABL1 are indicated with an arrow. (B) Sequencing chromatogram that was obtained four months subsequent to bosutinib administration. Only the T315I peak (ATT, indicated with an arrow) was detected.

Figure 3.

Summary of the clinical symptoms, blood analyses, and course of treatment for the present case report. Hepatosplenomegaly is indicated according to the size below the costal arches. mPSL, methylprednisolone; ALT, alanine transaminase; WBC, white blood cells; DRPM, doripenem; Neu, neutrophils; Hb, hemoglobin; Plt, platelets; G-CSF, granulocyte-colony stimulating factor (filgrastim); RCC 2U, 2 units of red cell concentrates; PC 10U, 10 units of platelet concentrates.

Figure 4.

The patient's leukemia load was reduced with administration of bosutinib. (A) Hematoxylin and eosin staining of bone marrow biopsy samples that were collected prior to and 1 and 4 months subsequent to the administration of bosutinib. A reduction in cellularity was observed with time. Original magnification, ×40. (B) Plain abdominal computed tomography scans were obtained prior to and 1 and 4 months subsequent to administration of bosutinib. Spleen volume was reduced following one month of bosutinib treatment. For the next three months, this reduced spleen volume was maintained.