[Rinsho ketsueki] The Japanese journal of clinical hematology最新文献

Sustaining lifelong hematopoiesis requires maintenance, proliferation, and differentiation of hematopoietic stem cells. Thrombopoietin is a cytokine essential for regulation of hematopoietic stem cells as well as differentiation and maturation of megakaryocytes required for platelet production. Due to these properties, thrombopoietin agonists have been used to treat bone marrow failure syndromes such as aplastic anemia. Through analysis of thrombopoietin gene-deficient mice, my colleagues and I have demonstrated the mechanism of action of thrombopoietin receptor agonists in hematopoietic stem cell maintenance and differentiation. This review focuses on governance of homeostasis in the hematopoietic system by thrombopoietin signaling.

B-cell maturation antigen (BCMA)-targeting therapy is the most common approach to immunotherapy and cellular therapy for multiple myeloma (MM). Three major agents, CAR-T cells, bispecific antibodies, and ADC have been developed as novel therapeutic agents. CAR-T therapy showed favorable efficacy in the treatment of relapsed and refractory MM (RR MM) and was tried in early lines of therapy. Similarly, bispecific antibodies targeting BCMA or other targets have also shown promising effects in treatment of RR MM, and have been now tested in combination with other agents. Although issues such as poor fitness or exhaustion of T cells and increased susceptibility to viral infection remain to be fully resolved, novel immunotherapies and cellular therapies should further improve the prognosis of patients with RR MM.

The blood cancer field has played a pioneering role in advancing precision medicine, with milestones such as development of ABL1 inhibitors for chronic myeloid leukemia. The significance of gene mutation information in AML treatment has increased, evident in classifications and guidelines from organizations such as WHO and ELN. This article examines the anticipated roles of cancer genome panels (CGPs) in AML treatment from three perspectives: diagnosis, risk stratification, and treatment selection. Use of CGPs enables more accurate diagnosis and risk stratification. In treatment selection, CGPs not only complements but also substitutes existing companion diagnostics, and is expected to be a crucial information source for future drug adoption and investigation of tumor-agnostic therapies. However, various challenges remain to be addressed, including the purpose and timing of CGPs, the time required for the tests, and how to utilize expert panels.

Imatinib, the first ABL-tyrosine kinase inhibitor (TKI), was approved in 2000 for the treatment of chronic myeloid leukemia (CML). Second- and third-generation TKIs, as well as asciminib, which targets a different site of BCR-ABL1 (the myristoyl pocket), were later approved in 2022. Currently, six drugs are approved for the treatment of CML. Revisions to the clinical guidelines for hematopoietic tumors in 2023 provided new guidance on the utility of new agents as well as TKI dose reduction and treatment discontinuation. This article outlines recently reported predictions regarding TKI treatment response, the role of asciminib in the treatment of CML, and development of new agents, as well as the latest findings regarding the current state of TKI treatment discontinuation.

Health surveys to assess adverse events after peripheral blood stem cell harvest (PBSCH) have conventionally been conducted by phone, but phone calls are suboptimal for conducting frequent surveys. We developed a web-based application (donor app) that enables donors to inform healthcare professionals (HCPs) of their health status as an electronic patient-reported outcome (ePRO). In this prospective observational study, we compared the usefulness of this donor app to phone calls for conducting health surveys. App users reported ePRO daily, and patients called by HCPs reported their health status at least once a week when called. The observation period was from the first administration of granulocyte colony-stimulating factor to the first follow-up visit after PBSCH, excluding the hospitalization period. Each group consisted of eight donors with a median age of 32 years (range: 19-58). Nine (56.3%) were female. There were eight related donors in the phone call group and four in the donor app group. During the observation period, HCPs obtained health status reports more frequently from app users than from phone call recipients (mean proportion of days with reports made during the observation period, 27.0% vs 53.5%; p<0.05). Average time spent by the HCPs for one follow-up and total follow-ups were both significantly shorter when the donor app was used. There were no differences in donor burden or satisfaction with donation. Our study suggests that use of a donor app could provide more detailed health survey data without increasing the burden on donors and HCPs.

CAR-T cell therapy targeting CD19 and BCMA for relapsed or refractory hematopoietic tumors has been adopted in routine practice and has shown dramatic results. However, half of patients who achieve remission with CAR-T therapy eventually relapse, and thus efforts to improve the efficacy of CAR-T therapy are gaining momentum. Notably, studies have described innovative technologies that enable control of cell kinetics after infusion, which is not possible with conventional CAR-T therapies. In this article, we review the challenges of CAR-T cell therapy and the development of new technologies.

The causes of iron deficiency anemia include blood loss, increased demand, insufficient dietary intake, and disorders affecting iron absorption. In certain circumstances, atrophic gastritis, either autoimmune or due to Helicobacter pylori infection, may contribute. On very rare occasions, iron-refractory iron deficiency anemia can develop as a consequence of TMPRSS6 mutations. Iron deficiency anemia is diagnosed by identification of microcytic hypochromic anemia with low serum ferritin levels. In cases of chronic disorders such as chronic kidney disease, chronic heart failure, and chronic inflammatory disorders, the diagnosis may also incorporate transferrin saturation. Treatment of underlying diseases is recommended along with iron supplementation. While oral iron supplements are the first choice, intravenous iron may be considered when oral administration is impractical, iron absorption is impaired, or rapid iron replenishment is necessary. Recently, high-dose intravenous iron formulations became available in Japan, but their use requires caution due to potential risks of allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage. Notably, the benefits of high-dose intravenous iron for patients with heart failure and iron deficiency are recognized in the field of cardiology. This article provides an overview, incorporating recent developments in the field of iron deficiency anemia.

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.