Stable long-term control of GVHD after allogeneic hematopoietic stem cell transplantation is one of the key challenges in an era of increasingly diverse transplant modalities. Over the past decade, the development of objective criteria for the diagnosis and evaluation of GVHD and advances in our understanding of the biological pathways of GVHD pathogenesis have led to steady progress in the development of novel agents. Until recently, calcineurin inhibitors and steroids have dominated the management of GVHD in transplantation, however, in recent years, T-cell depletion therapy to limit donor T-cell proliferation in the acute phase and the patient-oriented target therapy to minimize steroid exposure and suppress the specific pathogenesis are being considered. The development and clinical implementation of biomarkers to identify pathologic pathways in individual patients will be the basis for appropriate post-transplant immune management. The establishment of the clinical approach based on objective information will greatly accelerate the trend toward personalized medicine in immune managements, leading to safe and long survival with satisfactory QOL.

 Chimeric antigen receptor (CAR)-engineered T-cell therapy can induce a high remission rate for B-cell tumors and multiple myeloma. However, a significant number of patients experience a relapse after a transient response. To improve the efficacy of CAR-T cell therapy, genetic modification focused on epigenetic factors and cytokine signaling has been actively explored to confer long-lived potential and resistance to exhaustion of CAR-T cells. Studies are also underway to prevent or mitigate therapeutic toxicities, such as cytokine release syndrome, which inevitably increase in proportion to the therapeutic effect. In addition, the risk of developing T-cell malignancies after CAR T-cell therapy is better understood, and there is increasing interest in the long-term safety of the therapy. Here, I will review recent studies and future directions in CAR T-cell therapy with respect to the above perspectives.

 In Okinawa prefecture, bone marrow transplantation from related donors have been performed since the 1990s, and the number of transplantations has reached approximately 40 cases per year since 2000. Medical examination of hematological malignancies in Okinawa is characterized by much higher incidence of adult T-cell leukemia-lymphoma, which is extremely intractable and is required for stem cell transplantation in most cases, as well as by responsibility for medical care in remote islands and remote areas. It is therefore critical to establish a complete form of transplant service within the prefecture. Due to unwelcome medical accidents along with a serious shortage of hematologists, stem cell transplantation at the University of the Ryukyus hospital was previously interrupted two times. For this, transplantation through the Japan Marrow Donor Program was unavailable for a long period of time, and patients had to face a heavy burden financially, mentally, and physically. Subsequently, the University of the Ryukyus hospital was re-accredited as an unrelated donor transplantation facility, and currently, transplantations are performed solely in the University hospital among eight specialized facilities in Okinawa. We here overview the history of stem cell transplantation therapies for blood cancers in Okinawa with a specific emphasis on future prospect.

 The time period required for immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be very long and is influenced by various factors, such as the type of conditioning regimen, immunosuppressive drugs used, the development of graft-versus-host disease, and its treatment. Consequently, patients often develop various infections, sometimes with fatal outcomes, owing to severe and persistent immunodeficiency. Recent advancements in antibiotic, antifungal, and antiviral drug therapies have improved allo-HSCT outcomes, especially by reducing non-relapse mortality. However, infections remain a major post-transplant complication, accounting for more than 20% of deaths after allo-HSCT. Thus, assessing each patient’s risk factors for infection over time and implementing appropriate prevention and treatment strategies accordingly is critical for controlling infections after allo-HSCT. This review summarizes the latest evidence on prevention and treatment strategies for fungal and cytomegalovirus infections after allo-HSCT, which have seen remarkable progress in recent years.

 Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment aimed at curing acute myeloid leukemia (AML). However, allo-HSCT is associated with a high treatment-related mortality rate and a decline in post-transplant quality of life, necessitating careful implementation based on prognostic considerations.

 In AML, numerous genetic mutations are involved in its development and relapse, and stratifying AML prognosis based on genetic mutations at the time of initial diagnosis is crucial. For example, FLT3-ITD has been considered a poor prognostic factor; however, it has become evident that prognosis varies depending on coexisting mutations such as NPM1 and DNMT3A, the allelic ratio of FLT3-ITD, and the use of FLT3 inhibitors. Therefore, searching for minimal residual disease targeting NPM1 mutations and FLT3-ITD is also important to enable individualized treatment based on therapeutic responsiveness.

 This article outlines the significance of genomic analysis in determining eligibility for allo-HSCT in AML.

 Chronic graft-versus-host disease (GVHD) is a complication that occurs after allogeneic hematopoietic cell transplantation. It presents with symptoms similar to autoimmune diseases, targeting various organs such as the skin, eyes, mouth, lungs, esophagus, gastrointestinal tract, liver, muscles, joints and fascia, reproductive organs, and serous membranes. In recent years, insights from animal models on the mechanism of onset have increased, establishing a three-step model that begins with acute inflammation, progresses through chronic inflammation and immune dysregulation, and ultimately leads to tissue fibrosis and residual sequelae. The pathological mechanisms have been elucidated to include Th17 cells, Tc17 cells, regulatory T cells, follicular helper T cells, B cells, macrophages, and fibrosis-promoting factors. Furthermore, the National Institutes of Health Consensus Project has structured the scheme for drug development, and currently, the development of molecular targeted therapies aimed at various mechanisms is progressing worldwide. In Japan, extracorporeal photopheresis, a BTK inhibitor, a JAK inhibitor, and a ROCK2 inhibitor have been approved. Overseas, the approval of an anti-CSF-1 receptor antibody has preceded.

 At the post-transplant long-term follow-up (LTFU) outpatient clinics, healthcare staff need to screen and intervene diverse issues ranging from physical and psycho-social late effects. A nationwide survey of post-transplant LTFU clinics conducted in 2018 showed that many facilities continue follow-up beyond 5 years after transplantation. This suggested that reducing the burden on healthcare staff as well as the standardization of LTFU care was necessary, and these were expected to promote the nationwide policy to establish a medical care delivery system in which post-transplant survivors have access to appropriate long-term post-transplant care regardless of where they live. The survey showed a high demand for nationwide LTFU tools such as information materials on late complications. To date, seven types of LTFU tools, including a tool to support pediatric-adult transition, have been created and are available on the JSTCT website. The third national LTFU survey in 2024 was planned also to investigate the utilization and demands for released tools.

 Oral complications frequently occur in hematopoietic stem cell transplantation (HSCT) patients and can impair local and systemic conditions. In 2022, the Japanese Society for Transplantation and Cellular Therapy, along with the Japanese Association of Oral Supportive Care in Cancer, published “Position Paper on Oral Management for Hematopoietic Cell Transplant Patients”, which includes detailed recommendations for multidisciplinary oral management with explanations and citations. This review provides an overview of these recommendations. Moreover, after the publication of this paper, relevant international societies have issued statements and guidance that can serve as references for oral management in HSCT patients. This review also introduces this information.

 Extracorporeal photopheresis (ECP) has become a new treatment option for steroid-resistant/intolerant chronic graft-versus-host disease (GVHD) in Japan. However, few facilities have introduced ECP therapy, and the areas where it is available are limited. Since it is thought to be due to human resource issues, we investigated the workload of medical professionals involved in ECP treatment. It was found that one ECP treatment took an average of about two hours, but the average treatment time was significantly shorter in cases where the double-needle mode, which allows blood to be drawn and returned simultaneously, was selected. And the average time involved by nurses and clinical engineers was significantly shorter in facilities where ECP treatment was performed in the hemodialysis center. Although there were differences in ECP treatment time and the time spent by medical professionals depending on the method of venous access and the location of the facility where ECP was performed, the workload of medical professionals was high. In the future, it will be necessary to share information on efforts to reduce the workload of medical professionals for the establishment of a system that can provide ECP treatment to patients requiring ECP treatment.

 Immune Reconstitution Inflammatory Syndrome (IRIS) is a complication that develops after anti-HIV treatment in patients with HIV (human immunodeficiency virus) /AIDS (acquired immunodeficiency syndrome) after anti-HIV treatment. This phenomenon is known as immune recovery aggravating an existing infection. IRIS can also occur after chemotherapy or organ transplantation. This report describes the case of a 10-year-old boy with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph＋ALL). He developed Candida parapsilosis infection after bone marrow transplantation, which was followed by Pneumocystis pneumonia. While the patient’s immune system recovered, his condition progressed to respiratory failure due to excessive inflammation. His symptoms improved with respiratory management and steroid therapy. IRIS is characterized by worsening inflammation in specific infections and affected organs, with a particularly high risk during invasive fungal infection. The diagnosis and early treatment of IRIS are important, and the use of appropriate steroid therapy is crucial.