Rash caused by lenalidomide, a key therapeutic agent for multiple myeloma (MM), often interferes with treatment continuation. This study investigated whether thymus and activation-regulated chemokine (TARC), a Th2-related chemokine, could serve as a biomarker for lenalidomide-induced rash. We evaluated patients treated with lenalidomide for MM at Takarazuka Municipal Hospital between January 2016 and October 2023. TARC levels were measured in patients who developed grade ≥2 rash. Clinical information, including blood test results, management of rash, and subsequent clinical course, was collected from medical records. Each episode was defined as one event consisting of three time points: before lenalidomide initiation, at rash onset (when TARC was measured), and at rash resolution. Fourteen events in eleven patients were analyzed. In all events, TARC levels were elevated at rash onset. In contrast, elevations in general inflammatory markers (white blood cell count, eosinophils, and C-reactive protein) or in lactate dehydrogenase, an indicator of atopic dermatitis, were observed in only a minority of events. These findings suggest that TARC may be a useful biomarker for identifying lenalidomide-induced rash and may aid in optimizing clinical management while maintaining treatment continuity.

In the 5th edition of the WHO classification, Epstein-Barr virus (EBV)-positive nodal T/NK-cell lymphoma (EBV⁺ nTNKL) is a newly defined, poor-prognosis disease originating from cytotoxic T cells. Here, we report a rare case of lymphoma arising in immune deficiency/dysregulation with an immunophenotype of EBV⁺ nTNKL that emerged during treatment for follicular lymphoma (FL). A 71-year-old woman was diagnosed with FL grade 3A and received chemotherapy with rituximab. Despite treatment, the disease relapsed repeatedly. During follow-up, she presented with fever and lymphadenopathy. An axillary lymph node biopsy revealed a diffuse proliferation of abnormal lymphocytes expressing CD3, CD4, TIA-1, granzyme B, and EBER, consistent with the EBV⁺ nTNKL immunophenotype. CHOP therapy was administered; however, disease control proved difficult, and the patient died 5 weeks after diagnosis. This case exemplifies a rare occurrence of EBV-associated lymphoma arising during the course of B-cell lymphoma. Our experience underscores that rapid clinical deterioration (e.g., fever, hepatosplenomegaly, or B symptoms) during the course of FL should prompt consideration of EBV-associated lymphoma in the differential diagnosis, alongside histologic transformation. Further case reports and molecular analyses should help improve diagnostic accuracy and establish treatment strategies for this rare and aggressive disease.

Background: Acquired factor V deficiency is a rare bleeding disorder caused by autoantibodies against factor V, resulting in marked reduction of activity and bleeding tendency. Case Presentation: We report the case of an 81-year-old man who developed acquired factor V deficiency after total arch replacement and open stent grafting for a thoracic aortic aneurysm. Postoperatively, despite the absence of bleeding tendency, both prothrombin time (PT) and activated partial thromboplastin time (APTT) were markedly prolonged. Factor assays revealed factor V activity <3%, and a factor V inhibitor was detected (1 BU/ml). A cross-mixing test indicated a pattern of factor deficiency, suggesting the involvement of clearance-facilitating antibodies in addition to neutralizing antibodies. Discussion: Acquired factor V deficiency is often associated with surgery, transfusions, or antibiotics. Although rare, it should be considered in patients with unexplained prolongation of PT and APTT. Cross-mixing tests may mimic factor deficiency patterns when clearance-facilitating antibodies are present, requiring careful interpretation. Immunosuppressive therapy including corticosteroids, cyclophosphamide, or rituximab has been reported effective, while bleeding episodes may be managed with plasma or bypassing agents. Conclusion: This case emphasizes the importance of considering acquired factor V deficiency in the differential diagnosis of postoperative coagulopathy with unexplained prolongation of PT and APTT.

Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has shown high efficacy in relapsed or refractory large B-cell lymphoma (R/R LBCL). However, treatment options are limited for patients who fail to achieve durable remission after immune-based therapy. Here, we describe a case of refractory diffuse large B-cell lymphoma in an 87-year-old woman who achieved long-term remission through concurrent epcoritamab and radiotherapy. During the fifth cycle of third-line epcoritamab therapy, positron emission tomography/computed tomography revealed persistent fluorodeoxyglucose-avid lesions in the spleen and mediastinum. Volumetric modulated arc therapy of 36 Gy in 18 fractions was administered to both sites while continuing epcoritamab (administered during the sixth cycle for the splenic lesion and during the thirteenth and fourteenth cycles for the mediastinal lesion). The combined therapy resulted in complete metabolic response without significant adverse events, and the patient remains in remission beyond 27 treatment cycles. In this case, we obtained durable remission by adding radiotherapy for localized lymphoma refractory to epcoritamab. The absence of cross-resistance between radiotherapy and systemic chemotherapy supports the rationale for local irradiation as a complementary approach to bispecific antibody therapy. This combination may represent a feasible and well-tolerated option for elderly or heavily pretreated patients with localized refractory disease.

A 71-year-old woman was found to have pancytopenia during a routine health check-up and was referred to a local hospital. Bone marrow examination did not yield a definitive diagnosis, and the cytopenia gradually progressed over the following two years. She was subsequently referred to our institution for further evaluation, including assessment of eligibility for hematopoietic stem cell transplantation. ¹⁸F-Fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) revealed massive splenomegaly without abnormal FDG uptake. Given the concurrent infection suspected to be fungal pneumonia, a splenectomy was performed for diagnostic and therapeutic purposes. Histopathological examination of the resected spleen, together with T-cell receptor gene rearrangement analysis, led to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). Following splenectomy, hematologic recovery was achieved rapidly, and CHOP chemotherapy was administered. The patient has remained in remission for approximately one year without evidence of relapse. Although HSTCL generally has a poor prognosis, this case is notable in that splenectomy both established the diagnosis and led to marked improvement in pancytopenia.

Advances in hemophilia care have markedly improved bleeding control and extended life expectancy, bringing age-related comorbidities to the forefront. Ischemic heart disease (IHD) and other thrombotic events are no longer rare in real-world practice. While observational studies from Europe and North America report that 5% to 8% of patients experience IHD-related events, earlier Japanese retrospective data suggested a much lower burden. In the nationwide prospective ADVANCE Japan cohort of adults with hemophilia aged ≥40 years, IHD-related events have been observed during follow-up, highlighting the need for contemporary evidence from Japan. Moreover, comparisons between predicted and observed events indicate potential miscalibration of general population—derived risk models (e.g., QRISK and the Suita score) when applied to hemophilia. For acute coronary syndromes and PCI, peri-procedural hemostatic management—ensuring adequate factor VIII/IX activity, optimizing access strategy, and coordinating antithrombotic intensity—is essential. Shortened dual antiplatelet therapy regimens supported by trials in high-bleeding-risk populations may be informative, but extrapolation requires individualized assessment. The role of direct oral anticoagulants, including in patients receiving emicizumab, remains uncertain. Multidisciplinary care and shared decision-making are pivotal to balancing bleeding and thrombosis risks in the aging hemophilia population.

The current standard of care for smoldering multiple myeloma (SMM) is active surveillance. In Japan, daratumumab has been approved for the treatment of high-risk SMM. Identification of patients most likely to benefit from treatment is essential to prevent end organ damage through early intervention in patients with high-risk SMM while avoiding unnecessary toxicity by selecting active surveillance for lower-risk patients. Risk stratification models based on clinical biomarkers have been developed. Recently, understanding of disease biology has improved with the advent of comprehensive genetic analysis of tumors and the tumor immune microenvironment. Newer risk models integrating genetic biomarkers into clinical parameters are currently being developed. Clinical trials have also evaluated treatment efficacy and safety in patients with high-risk SMM based on each risk model. Recommendations for early intervention must be underpinned by robust evidence demonstrating not only delayed progression but also improved quality of life and/or overall survival.

Multiple myeloma is an incurable hematologic malignancy; however, survival outcomes have improved with the introduction of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. As autologous transplantation remains the standard therapy, transplant eligibility determines the treatment strategy for newly diagnosed myeloma. Quadruplet first-line regimens were approved in 2025 and became the standard of care regardless of transplant eligibility, improving clinical outcomes. Minimal residual disease (MRD) has been identified as a surrogate marker for survival, and MRD negativity is increasingly being adopted as the primary endpoint in clinical trials. Autologous transplantation is associated with higher MRD negativity rates, but its necessity for patients who achieve MRD negativity may be open to debate. Furthermore, ongoing clinical trials are comparing autologous transplantation with CAR-T cell therapy and incorporating BCMA-targeted immunotherapies, including bispecific antibody drugs, into post-transplant maintenance therapy. This review summarizes treatment strategies for newly diagnosed myeloma in the era of quadruplet combination therapy.

The development of triple-class regimens incorporating immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies has extended progression-free survival in multiple myeloma (MM) patients. Furthermore, in recent years, novel BCMA- and GPRC5D-targeted T-cell redirection therapies, including chimeric antigen receptor (CAR) T-cell and bispecific antibody therapies, have yielded remarkable advances in MM treatment. This review discusses several factors influencing treatment efficacy and safety in this new era of immunotherapy.

Systemic AL amyloidosis is a progressive disorder characterized by deposition of immunoglobulin light chain-derived amyloid fibrils in multiple organs, resulting in diverse clinical manifestations. A definitive diagnosis requires histopathological confirmation of amyloid deposition, and delayed diagnosis is closely associated with poor outcomes. The current standard frontline therapy for newly diagnosed patients is the combination of daratumumab, cyclophosphamide, bortezomib, and dexamethasone, which has demonstrated high hematologic and organ response rates. Autologous hematopoietic stem cell transplantation can induce deep and durable hematologic responses; however, transplant-related mortality remains higher than in multiple myeloma, necessitating careful patient selection. For relapsed or refractory cases, conventional anti-myeloma agents such as lenalidomide, pomalidomide, and ixazomib remain options, while emerging therapies including venetoclax and BCMA-targeted approaches show promising efficacy. Investigational strategies targeting amyloid fibrils are also under active development, although their clinical benefit remains to be fully established. Advances in early diagnosis and novel therapeutic approaches are essential to improve outcomes in systemic AL amyloidosis.

POEMS syndrome is a rare multisystemic disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell dyscrasia, and skin changes. Markedly elevated serum vascular endothelial growth factor (VEGF) levels play a crucial role in its pathogenesis. Recent genomic studies have identified specific mutational patterns in the immunoglobulin lambda light chain gene (e.g., IGLV1-40 or IGLV1-44), providing new insights into the unique biology of POEMS syndrome. For clinical diagnosis, the Japanese diagnostic criteria are highly practical and accurate, designating polyneuropathy, monoclonal plasma cell proliferation, and elevated serum VEGF levels (>1,000 pg/ml) as mandatory major criteria. Treatment strategies are determined based on eligibility for autologous stem cell transplantation (ASCT). For eligible patients, high-dose melphalan followed by ASCT is the standard of care, yielding significant neurological improvement and favorable long-term survival. In contrast, for transplant-ineligible patients or as induction therapy before ASCT, novel agents such as thalidomide, lenalidomide, and bortezomib have demonstrated clinical efficacy. Serum VEGF levels serve as an essential biomarker that sensitively reflects disease activity and treatment response, making them indispensable for monitoring during follow-up. This review provides a comprehensive overview of recent advances in the pathogenesis, diagnostic refinements, and latest therapeutic strategies for POEMS syndrome based on recent scientific evidence.