[Rinshō ketsueki] The Japanese journal of clinical hematology
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Standard treatment for acute myeloid leukemia (AML) comprises (1) induction therapy with both cytarabine and anthracycline and (2) consolidation therapy that is modified according to patients' conditions, including prognostic factors. However, this strategy is not satisfactory, especially for elderly patients. Novel technologies have revealed several driver mutations of numerous critical genes in AML, which can be targeted by novel drugs; the discovery of such targetable genes and the development of novel drugs have evolved the treatment strategy for AML. ⋯ In the United States, the FDA has already approved several new drugs for AML, including FLT3 inhibitors and IDH neoenzyme inhibitors. In Japan, gilteritinib, an FLT3 inhibitor, was also approved at the end of 2018. These promising drugs will facilitate performing "precision medicine" on patients with AML soon.
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Inherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes associated with DNA repair and telomere maintenance. In addition, mutations in ribosome-related genes cause defective hematopoiesis. Patients with IBMFS exhibit a predisposition to developing hematological malignancy or solid tumor because of the defect in cellular and molecular hemostasis. ⋯ Recently, monocytopenia and mycobacterial infection (MonoMAC) syndrome with the GATA2 gene mutation have been reported as PID related to bone marrow failure. Patients with MonoMAC syndrome often develop MDS and acute myeloid leukemia. Here, we present the pediatric-onset IBMFS and/or PID with cancer predisposition and briefly discuss the tumorigenesis in each monogenic disease.
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Imatinib, nilotinib, dasatinib, bosutinib, and ponatinib are tyrosine kinase inhibitors used to treat chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and target concentration intervention (TCI) are novel strategies that use concentration-controlled dosing (CCD) to attain a faster and more profound clinical response in patients with CML. The target plasma trough concentration (C0) of imatinib is 1,000 ng/ml to obtain a higher major molecular response (MMR) rate. ⋯ Approaches for these four TKIs involve the use of TCI with specific target concentrations rather than TDM with a therapeutic range. Conversely, for dasatinib, a lower C0 of <4.33 ng/ml is the maximum toxic concentration recommended to avoid pleural effusion. Therefore, precision dosing using CCD of TKIs for CML could maximize the clinical benefit and minimize toxicity.
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In the treatment of hemophilia patients, factor (F) VIII or FIX product prophylaxis results in arthropathy prevention and quality of life (QOL) improvement. Serious issues concerning hemostatic treatment of hemophilia include frequent intravenous administration of products, inhibitor development, and hemostatic treatment of patients with inhibitors. To overcome these challenges, products with extended half-life were developed. ⋯ Two therapies, namely si-RNA anti-antithrombin therapy and anti-TFPI antibody therapy, aimed at rebalancing coagulation, are also under development. In addition, a gene therapy for hemophilia B has been developed by improving the vector. These new therapies could further improve the QOL of hemophilia patients.
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Review Case Reports
Myelodysplastic syndrome with myelofibrosis in which azacitidine therapy was effective and cord blood transplantation was carried out.
Myelodysplastic syndrome with myelofibrosis (MDS-F) is a disease with a poor prognosis, and patients with this condition are at an increased risk of engraftment failures after allogeneic hematopoietic stem cell transplantation (SCT). Azacitidine (AZA) is effective in high-risk MDS patients. However, the effects of AZA on MDS-F have not been elucidated. ⋯ He developed acute graft versus host disease (GVHD) of the skin (stage 3/grade II), but it could be controlled using prednisolone. Chronic GVHD was not observed and he was discharged in good general condition on day 68. While treatment prior to allogeneic SCT of MDS-F has not been established, in the present case, the hematological improvement brought about by AZA likely contributed to the patient's positive response to UCBT.