[Fatal exacerbations of chronic active Epstein-Barr virus infection subsequent to cytotoxic chemotherapy].

Chronic active Epstein-Barr virus infection (CAEBV) is critical owing to lethal complications such as hemophagocytic lymphohistiocytosis (HLH), multiple organ failure, and malignant lymphoma. Here we present two cases of CAEBV who developed rapid and life-threatening disease progression after cytotoxic chemotherapy. Case 1: In a 34-year-old male, CAEBV recurred after 4-month remission obtained by initial therapy with etoposide, cyclosporine, and prednisolone. Accordingly, cord blood transplantation was planned. A day after administering high-dose melphalan as the conditioning, he developed respiratory failure, pancytopenia, and hyperferritinemia. He died 3 days later. Case 2: A 53-year-old female attained remission after initial therapy for CAEBV. After 1 month, she relapsed, and high-dose cytarabine (HDAC) was administered. A day after HDAC administration, she suddenly developed respiratory failure, which was followed by multiple organ failure. She died 3 days later. Thus, planned strategy for prompt allogeneic hematopoietic stem cell transplantation is necessary to prevent disease progression and control cytokinemia before cytotoxic chemotherapy for CAEBV.

[Blastic plasmacytoid dendritic cell neoplasm accompanied by chronic myelomonocytic leukemia successfully treated with azacitidine].

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease that develops with a skin lesion and is often accompanied by leukemic transformation. The normal counterparts of BPDCN tumor cells are progenitors of plasmacytoid dendritic cells, whereas the origins are thought to be hematopoietic stem cells. Approximately 10%-20% of BPDCN patients develop other hematologic malignancies, including chronic myelomonocytic leukemia (CMML). Mutations in epigenetic regulators are frequently observed in both BPDCN and CMML tumors. Azacitidine, a drug that targets epigenetic dysregulation, is known to be an effective treatment for CMML. However, it has been used in few BPDCN patients. Here, we report a BPDCN patient with skin lesions, bone marrow infiltration, and lymphadenopathy. CMML also developed during the course of BPDCN. Azacitidine had positive effects on CMML; however, BPDCN aggressively relapsed during treatment. Two TET2 mutations were found in both BPDCN and CMML tumors; one of which was commonly identified in both tumors.

Salvage Cord Blood Transplantation Using a Short-term Reduced-intensity Conditioning Regimen for Graft Failure.

Objective Graft failure (GF) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). A standardized conditioning regimen and an appropriate graft source of salvage HSCT for GF have not yet been established. Some case series have shown good hematopoietic recoveries after salvage HSCT using a short-term reduced-intensity preparative regimen consisting of fludarabine (30-90 mg/m2), cyclophosphamide (2 g/m2), and total-body irradiation (2 Gy). However, the dose of fludarabine has varied in these reports based on the clinical condition of the patients, resulting in very limited experiences with each dose of fludarabine. Methods We retrospectively analyzed 10 patients who developed GF after allogeneic HSCT and underwent salvage cord blood transplantation (CBT) using the above-mentioned conditioning regimen with a fixed dose (90 mg/m2) of fludarabine. Results Eight patients (80.0%) achieved neutrophil engraftment within 30 days from salvage HSCT with a median of 21 (range, 17-23) days. The 1-year overall survival (OS) rate after the salvage HSCT was 50.0%, and the median OS was 281 (range, 23-1,638) days. Cumulative incidences of non-relapse mortality and relapse at 1 year were 50.0% and 10.0%, respectively. Conclusion CBT using this short-term reduced-intensity conditioning regimen may be a promising salvage therapy for GF.

Dasatinib Is an Effective Treatment for Angioimmunoblastic T-cell Lymphoma.

Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10-78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment. SIGNIFICANCE: Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib.

Invasive Thymoma with Pure Red Cell Aplasia and Amegakaryocytic Thrombocytopenia.

We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6 × 104/µL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT). On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaokakoga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention.