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The patient was a 68-year-old woman, diagnosed with acute myelomonocytic leukemia with normal karyotype and FLT3-ITD-negative status in May 2019. She had achieved complete remission (CR) after "7+3" intensive induction chemotherapy and maintained CR by consolidation chemotherapy. However, she relapsed with swelling of the lips and gums in January 2020. She did not achieve CR by salvage chemotherapy with cytarabine-aclarubicin-G-CSF regimen. Comprehensive genomic analysis of leukemic cells revealed the presence of FLT3-N676K mutation, which was undetectable by companion diagnostics at the time. Complete remission with incomplete count recovery was obtained on day 28 after initiation of gilteritinib monotherapy, and the lip and gum swelling improved rapidly. However, she relapsed on day 106 after gilteritinib administration, and gilteritinib was discontinued. Genomic analysis at recurrence revealed NRAS mutation for the first time. Finally, the patient died of the uncontrolled primary disease. This is a case in which comprehensive gene mutation analysis was useful in determining a treatment strategy.

Tyrosine kinase inhibitors (TKIs) are highly effective in the treatment of chronic myelogenous leukemia (CML), but there have been a few adverse event reports describing gastrointestinal bleeding. We clinically analyzed two patients who developed intestinal bleeding during the administration of TKIs for CML. Platelet counts of both patients were normal. The patients showed endoscopic findings characterized by mildly hemorrhagic mucosa. The imatinib patient was diagnosed by capsule endoscopy of the small intestine, and required frequent blood transfusions. The dasatinib patient showed occult bleeding due to CD8-positive colitis. We should adequately recognize that gastrointestinal bleeding may occur during the administration of TKIs.

Imatinib mesylate (imatinib) has shown significant effects in patients with chronic myelogenous leukemia. However, hematological toxicity often occurs and requires dosage reduction or discontinuation of imatinib treatment. A patient with chronic myelogenous leukemia in the blastic crisis received granulocyte-colony stimulating factor (G-CSF) simultaneously with imatinib. The patient was continuously treated with imatinib and G-CSF and achieved remission without any severe infection or neutropenia. There are a few reports on the efficacy of combined therapy with G-CSF and imatinib; however, the results in our case are rare suggesting that the use of G-CSF is effective for preventing severe infection. G-CSF enables continuous treatment with high-dose imatinib.

A 60-year-old woman was admitted to our hospital to receive treatment for relapse of biphenotypic leukemia 4 years after her initial presentation. Bone marrow examination revealed 53.5% lymphoblasts, which were classified as ALL-L2 with a normal karyotype. Lymphoblast surface markers were positive for cells of both B-cell and myeloid lineage. Immunoglobulin heavy chain and T-cell receptor gene rearrangements were investigated with PCR. Clonal rearrangement of TCR delta V delta 2-D delta 3 was detected. The same clonal rearrangement of TCR delta was found using frozen initial leukemic cells. Rather than secondary leukemia, the patient's leukemia was confirmed as relapse of the initial clone. Detection of the clonal rearrangement was also useful as a patient-specific marker for minimal residual disease.