The optimal regimen for refractory acute myeloid leukemia (AML) in the elderly with good performance status has not been established. A 71-year-old man was admitted to our hospital with pancytopenia and 1.0% blasts in the peripheral blood. The patient was diagnosed with AML with DNMT3A (R882H)- and IDH2 (R172K)-positive myeloblasts. He received a reduced dose of idarubicin and cytarabine therapy. However, induction failure with 20% bone marrow blasts and DNMT3A mutations were observed. A reinduction therapy with venetoclax and azacitidine (VEN+AZA) was administered and led to a sustained complete response with significantly reduced DNMT3A-mutated blasts. Even 9 months after starting VEN+AZA, the patient is still alive and healthy without AML recurrence. Thus, VEN+AZA therapy may be highly effective for treating IDH2- and DNMT3A-mutated AML in elderly patients.

Herein, we report the findings of a 79-year-old male patient who presented with multiple extramedullary plasmacytomas following a relapse of primary plasma cell leukemia. He developed thrombotic microangiopathy (TMA) while receiving carfilzomib, lenalidomide, and dexamethasone (KLd) therapy. He was diagnosed with plasma cell leukemia 3 years ago; he demonstrated a very good partial response (VGPR) after undergoing two regimens, including either bortezomib or lenalidomide, and he had been followed up without any other treatment due to complications of infection. Following relapse, KLd was initiated. On day 7 of KLd, TMA developed; therefore, the treatment was discontinued. The TMA improved only with the discontinuation of KLd. A reduced dose of KLd was readministered; the TMA did not relapse. He demonstrated VGPR after three courses of reduced-KLd; he has since remained in remission through ten courses. Therefore, carfilzomib therapy may be useful in relapsing and refractory cases. Drug-induced TMA has been reported to be caused by either immune-mediated or dose-dependent toxicity mechanisms. In patients who develop dose-dependent TMA with carfilzomib, dose reduction could be considered in cases showing an effective response to the treatment.

A 54-year-old woman was referred to our hospital for pancytopenia and liver dysfunction, and with no personal or family history of hemophagocytic lymphohistiocytosis (HLH). Although the etiology was unknown, she was diagnosed with HLH. She experienced exacerbation of HLH even after initiating systemic chemotherapy with etoposide, dexamethasone, and cyclosporine. Furthermore, flow cytometric analysis of the natural killer cells revealed a reduction in perforin expression, and DNA sequencing of the perforin gene (PRF1) revealed two known mutations, confirming the diagnosis of late-onset familial HLH type 2. She received an allogeneic stem cell transplant from an unrelated human leukocyte antigens identical donor, but developed thrombotic microangiopathy, and succumbed to septic shock shortly after the transplant. Previously, HLH in adults was believed to develop from underlying diseases. However, as in our case, several reports demonstrated that HLH gene mutations could be found even after adolescence. Adult with HLH with no underlying disorders should undergo early HLH-associated gene testing for confirmatory diagnosis.

Essential thrombocythemia gradually developed into secondary myelofibrosis and progressed to leukemia eight months later in a 53-year-old man. After remission induction therapy, he achieved remission by undergoing allogeneic hematopoietic stem cell transplantation from unrelated patients in non-remission. However, peripheral blood WT-1 mRNA gradually increased, and the disease relapsed three years and six months after transplantation. He was taking prednisolone (7.5 mg) and tacrolimus (5 mg) for chronic pulmonary graft-versus-host disease (GVHD) and was reluctant to reduce or discontinue immunosuppressive drugs; therefore, donor lymphocyte infusion (DLI) was performed for a total of five times. Four months after the fifth DLI, cutaneous GVHD appeared, a slow decrease in WT-1 mRNA was observed, and blasts in the peripheral blood disappeared. One year and three months after the last DLI, he achieved complete remission. Although DLI for post-transplant relapse in patients with secondary myelofibrosis or leukemia is rare, it can be beneficial for post-relapse therapy.

A 62-year-old woman was presented at our hospital with visual disturbance. An ocular examination revealed bilateral Roth spots. Laboratory data revealed leukocytosis (236,200 µl) with an excess blast (11%). Physical examination and computed tomography (CT) showed systemic lymphadenopathy. A bone marrow examination revealed a composition of 9.2% blast. Chromosomal analysis on bone marrow cells revealed 46,XX,t (3;12)(q26.2;p13),t (9;22)(q34.1;q11.2) in 80% of metaphases (16/20). Inguinal lymph node biopsy revealed diffuse proliferation of myeloperoxidase (MPO)-positive abnormal cells. Fluorescence in situ hybridization analysis was used to detect the BCR-ABL1 fusion gene and split the signals of MECOM and ETV6. She was diagnosed with de-novo chronic myeloid leukemia (CML) extramedullary blast crisis. She received tyrosine kinase inhibitor (TKI) combination chemotherapy and allogeneic hematopoietic stem cell transplantation and achieved a major molecular response. In this study, we reported a case of CML in blast-phase initially presenting as extramedullary, in which cytogenetic and molecular analyses were useful in the staging method.

This report describes a 69-year-old man with eosinophilia that was detected during a medical check-up. A review of his medical history revealed that his absolute eosinophil count was 990/µl at the age of 55 and increased to 5,380/µl at the age of 69. Electrocardiogram revealed first-degree atrioventricular block at the age of 58, followed by ST-segment depression and a negative T wave at the age of 65. The echocardiogram was normal at the age of 65. We diagnosed him with FIP1L1::PDGFRA-positive chronic eosinophilic leukemia by detecting the FIP1L1::PDGFRA fusion gene by fluorescence in situ hybridization. He had no symptoms at the first visit; however, echocardiography and contrast-enhanced computed tomography revealed an abnormal structure, considered a thrombus, within the left ventricular apex and apex wall thickening. We initiated imatinib (100 mg/day), and the eosinophilia disappeared in a month. However, his cardiac impairment worsened, and he gradually developed symptoms of heart failure. This case is valuable because it shows the long-term course of the disease, with 15 years of laboratory findings until diagnosis. Our findings suggest that in cases of eosinophilia with an abnormal electrocardiogram, contrast-enhanced cardiac magnetic resonance imaging should be considered earlier.

A 65-year-old man was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia with no initial central nervous system (CNS) involvement. Complete remission was achieved after the induction therapy. However, during consolidation therapy, he developed septic shock and pneumocystis pneumonia, leading to interruption in chemotherapy and allogeneic transplantation. Subsequently, he achieved complete molecular remission and ponatinib maintenance therapy was initiated. Two years later, he developed left leg paralysis and was diagnosed with isolated CNS relapse; however, radiation therapy improved CNS lesions and paralysis. Thus, ponatinib maintenance therapy alone is inadequate in preventing CNS relapse in patients who have not completed systemic chemotherapy for CNS relapse prevention.

Peripheral T-cell lymphomas (PTCLs) are mature T-cell and natural killer (NK) cell neoplasms with poor prognosis and no available standard treatment. The 2016 revision of the World Health Organization classification of hematological malignancies recognized a new group of nodal T-cell lymphoma with T follicular helper cell phenotype due to the presence of a group of PTCLs, not otherwise specified. This new subgroup of tumors showed clinical and molecular similarities with angioimmunoblastic T-cell lymphoma (AITL). AITL patients have mutations in the Vav guanine nucleotide exchange factor-1 (VAV1) gene. We established a transgenic mouse model harboring VAV1 gene mutation. These mice developed tumors that mimic human T-lymphoblastic lymphoma and the newly proposed PTCL-GATA3 subtype. To develop personalized treatment strategies by analyzing subgroup-specific mouse models, our study supports the establishment of PTCL subgroups based on genetic alterations or gene expression profiles.