A 69-year-old woman was referred to our hospital due to hyperleukocytosis. We diagnosed acute myeloid leukemia and started induction therapy with the CAG regimen (aclarubicin, cytarabine and filgrastim). However, the patient was refractory to the initial treatment and developed quadriplegia, and a cerebrospinal fluid (CSF) test showed elevated blasts. We then performed intrathecal chemotherapy, and the number of blasts in CSF gradually decreased. But only two cycles of intrathecal therapy were possible due to severe methotrexate-induced mucositis. The leukemia cells had fms-like kinase 3-internal tandem duplication (FLT3-ITD), so we started treatment with oral gilteritinib. The patient then achieved hematological complete remission. Her paralysis was also resolving, and the CSF was clear of blasts for more than 6 months. Some reports show that gilteritinib may penetrate the CNS, and this case also supports the effectiveness of gilteritinib on CNS leukemia.

We report the case of a 48-year-old man who presented with fatigue and weight loss. A local physician observed elevated alkaline phosphatase levels, anemia, thrombocytopenia, and renal dysfunction. Fever also appeared, and the patient was admitted to our hospital. Computed tomography revealed hepatosplenomegaly, pleural and ascitic fluid, and left axillary lymphadenopathy. Bone marrow biopsy indicated hyperplasia with increased megakaryocytes and reticulin fibrosis. Axillary lymph node biopsy showed Castleman’s disease-like features. Liver biopsy revealed proliferation of reticulin fibrosis. Therefore, TAFRO syndrome was diagnosed and treatment with 1 mg/kg prednisolone was started. Anemia and thrombocytopenia improved, and after 24 weeks of treatment, serum hyaluronic acid and type IV collagen decreased to the normal range. Bone marrow biopsy after 18 weeks of treatment showed decreased reticular fibers. In TAFRO syndrome, improvement of liver and bone marrow fibrosis can be expected with adequate intervention, and serum hyaluronic acid and type IV collagen are useful for evaluating fibrosis.

Patient 1 was a 70-year-old woman with refractory diffuse large B-cell lymphoma who received allogeneic peripheral blood stem cell transplantation from an HLA-haploidentical related donor. Upper back pain appeared on day63, and Th8-Th9 pyogenic spondylitis was diagnosed based on magnetic resonance imaging (MRI). Blood culture on day14 identified Corynebacterium striatum as the causative bacteria of blood stream infection (BSI). The pyogenic spondylitis resolved after treatment with daptomycin for 2 months. Patient 2 was a 65-year-old man with relapsed angioimmunoblastic T-cell lymphoma who received bone marrow transplantation from an HLA-DR single-antigen-mismatched unrelated donor. Lower back pain appeared on day30, and L4-L5 pyogenic spondylitis was diagnosed based on MRI. Blood culture was negative. Daptomycin and clindamycin were selected for treatment based on the drug susceptibility of bacteria that had caused pre-engraftment BSI (Escherichia coli on day3 and Corynebacterium striatum on day9), and the pyogenic spondylitis resolved after 6 months of this treatment. Pyogenic spondylitis should be considered in the differential diagnosis of back pain accompanied by BSI before engraftment in allogeneic hematopoietic stem cell transplant recipients.

Myelodysplastic syndromes (MDS) are a group of heterogenous hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis in which clonal progenitor expansion occurs alongside impaired myelopoiesis. Inflammatory signaling activation due to dysregulated innate immunity is also a hallmark of MDS pathogenesis. We recently established a useful preclinical tool that recapitulates bona fide MDS phenotypes and gene expression profiles based on previously unreported co-mutations discovered during our clinical surveillance of mutations in patients with MDS. Notably, we focused unbiased transcriptome analysis on determining the distinct underlying mediators of MDS etiology, and identified excessive mitochondrial fission-mediated fragmentation in mutant HSCs and progenitors (HSC/Ps). We confirmed excessive mitochondrial fragmentation in HSC/Ps obtained from patients with MDS regardless of the mutational profile. Importantly, in vivo pharmacological inhibition of mitochondrial fission significantly attenuated inflammatory signaling activation, dysplasia formation and ineffective hematopoiesis phenotype, and prolonged survival of MDS mice, suggesting that excessive mitochondrial fragmentation could be a fundamental trigger of MDS pathogenesis. These findings provide new insights into the mechanistic basis of ineffective hematopoiesis, and a clue for targeting bone marrow failure caused by ineffective hematopoiesis in MDS.

VEXAS syndrome is a new disease entity characterized by the presence of cytoplasmic vacuoles in blood cells, X-linked autoinflammatory symptoms, and somatic variants in UBA1, which encodes an E1 ubiquitin-activating enzyme. Around 30-50% of VEXAS syndrome patients have concurrent MDS. We and others have recently analyzed clinical and genetic features of MDS associated with VEXAS syndrome and found that most of these cases are categorized in the low-risk subgroup with low bone marrow blast percentages. MDS associated with VEXAS syndrome tended to involve a smaller number of genes and lower-risk genetic alterations than classical MDS. In addition, anemia in MDS associated with VEXAS syndrome with active inflammation before treatment tended to respond well to steroids. In this review, we will present our recent findings together with others, focusing on the new disease entity and pathophysiology of VEXAS syndrome and clinical/genetic features of associated MDS.

Hematopoietic cell transplantation (HCT) is considered a curative treatment for hematological malignancies. However, HCT recipients often face complications such as graft-versus-host disease (GVHD) and disease relapse. Clinical factors like age and HLA disparity are recognized as risks for GVHD. Notably, sex-mismatched HCT, particularly with female donors and male recipients (F→M), is reported to increase the risk of chronic GVHD. This adverse effect of F→M HCT is thought to result from allogeneic immune response against minor histocompatibility antigens encoded on the Y-chromosome of a male recipient (HY-antigens). Indeed, antibodies against HY-antigens (HY-Abs) were detected three months after F→M HCT, and the cumulative number of HY-Abs was significantly associated with increased risks of chronic GVHD and non-relapse mortality. This review focuses on F→M HCT, shedding light on its impact in several clinical settings and presenting clinical evidence of its allogeneic response, encompassing GVHD and graft-versus-leukemia (GVL) effects. Additionally, potential clinical options to mitigate adverse effects in F→M HCT will be discussed. Further investigation is required to improve clinical outcomes and understand allogenic immunological reconstitution after F→M HCT.

Use of posttransplant cyclophosphamide (PTCy) for the prophylaxis of graft-versus-host disease (GVHD) has revolutionized the field of HLA-haploidentical stem cell transplantation, which was previously considered high-risk and only feasible in specialized centers. The rapid adoption of PTCy is attributed not only to its superior efficacy in suppressing GVHD but also to its affordability and the lack of need for specialized techniques or equipment to administer it. Recently, PTCy has gained attention for its potential effectiveness in GVHD prophylaxis beyond HLA-haploidentical stem cell transplantation. In a phase III trial (BMT CTN 1703 trial) in patients undergoing allogeneic HLA-matched stem cell transplantation with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly better among those who received PTCy-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. In Japan, a phase II clinical trial that investigated PTCy for GVHD prophylaxis following HLA-matched or 1-2 allele mismatched peripheral blood stem cell transplantation confirmed the efficacy and safety of this approach. Effective suppression of GVHD using PTCy is expected to enhance the safety of allogeneic transplantation, potentially improving transplant outcomes and offering hope for better patient care in the field of transplantation.