[Rinsho ketsueki] The Japanese journal of clinical hematology最新文献

A 25-year-old female patient was referred to our department due to fever and cervical lymphadenopathy. Computed tomography showed bulky mediastinal lesions and bilateral supraclavicular and axillary lymphadenopathies. Cervical lymph node biopsy revealed nodular sclerotic Hodgkin's lymphoma (NS-HL) comprised of large Hodgkin/Reed-Sternberg (HRS) cells with sheet-like aggregates. The patient was diagnosed with a syncytial variant (SV). Immunohistochemical staining of HRS cells was positive for CD30, PD-L1, and MYC and negative for Epstein-Barr virus encoding region (EBER). The patient was assigned clinical stage IIB according to the Lugano classification and the poor prognosis group according to the National Comprehensive Cancer Network (NCCN). Furthermore, treatment with AVD (adriamycin/vinblastine/dacarbazine) in combination with brentuximab vedotin (BV) was initiated to achieve a complete metabolic response. Histopathologically, SV has a high proportion of HRS cells, with high CD30-positive and low EBER-positive rates. Therefore, CD30-targeted therapies such as BV may be preferable for SV, even in localized NS-HL patients, thereby improving patient prognosis.

The patient was a 46-year-old man with a family history of malignant lymphoma. He presented with bilateral submandibular and cervical lymphadenopathy, which resolved spontaneously. However, approximately one year later, he was admitted to our hospital for treatment of systemic lymph node swelling and bacterial pneumonia. Inguinal lymph node biopsy showed residual lymph follicles with T-zone expansion and numerous Epstein-Barr virus encoding region in situ hybridization (EBER-ISH) positive B-cells. Epstein-Barr virus (EBV) was also detected in the plasma, and EBV encephalitis was diagnosed. Following antibiotic treatment, the lymph node swelling regressed, and the patient was discharged. Based on the characteristic family history, susceptibility to infections, and EBV viremia, we suspected a primary immunodeficiency syndrome. XMEN disease caused by a pathogenic mutation in the magnesium transporter 1 (MAGT1) gene was diagnosed by genetic testing. To the best of our knowledge, no cases of XMEN disease from Japan have been reported in the literature. It is important to consider genetic testing when primary immunodeficiency is suspected.

A 34-year-old man underwent unrelated bone marrow transplantation (BMT) for blast-phase chronic myeloid leukemia (CML). Molecular remission was achieved on day 29. Around day 600 after BMT, the patient developed blurred vision in the right eye. Peripheral blood major mRNA was undetectable on day 606. An ophthalmologic examination on day 613 identified circumferential iris thickening and anterior chamber hypopyon-like lesions in the right eye. Betamethasone and levofloxacin ophthalmic solutions were started on the same day. On day 624, the white lesion in the anterior chamber had resolved, but iris thickening persisted. On day 663, peripheral blood major BCR::ABL1 mRNA (IS) increased as well, and molecular relapse of CML was diagnosed. Dasatinib was started at 20 mg/day on day 6 after relapse, and blurred vision improved on day 10 after relapse. On day 27 after relapse, the white lesion in the anterior chamber and iris hyperplasia had also resolved. By day 147 after relapse, dasatinib was gradually increased to 100 mg/day. Molecular remission was achieved on day 161 after relapse. Three years later, the patient remains in remission on dasatinib therapy.

Immune-mediated thrombotic thrombocytopenic purpura (TTP) is characterized by systemic thrombosis and organ damage due to a significant reduction in ADAMTS13 enzyme activity caused by the production of anti-ADAMTS13 autoantibodies. The standard frontline treatments are supplementation of ADAMTS13 and the removal of inhibitory antibodies by plasma exchange, suppression of inhibitor generation by corticosteroid, and suppression of thrombosis formation by caplacizumab. Additionally, in recurrent or refractory cases, favorable outcomes have been reported using rituximab. It has been reported that low ADAMTS13 inhibitor titers result in false negatives, and these rise to detectable levels due to a reaction to the ADAMTS13 factor in the fresh frozen plasma used in plasma exchange. Here, we report a case where the ADAMTS13 activity was <10%, but the ADAMTS13 inhibitor was negative at the initial measurement. It is difficult to distinguish between congenital and immune-mediated TTP. We experienced a rare case in which the patient's life was saved by continuing treatment for immune-mediated TTP while conducting a thorough examination of differential diagnoses. This rare case is presented together with a review of the relevant literature.

Congenital protein C (PC) deficiency is a major thrombotic risk factor in the Japanese population that often leads to severe thrombosis and bleeding in the neonatal period. Treatment typically involves anticoagulation such as warfarin and heparin, with PC concentrates used in acute cases. Here we report the case of a 25-year-old woman diagnosed with severe congenital PC deficiency. She had recurrent episodes of purpura fulminans despite warfarin therapy. After a COVID-19 infection, she developed coagulopathy with poorly controlled thrombotic and bleeding complications, followed by DIC. Replacement therapy with protein C concentrate led to rapid improvement in DIC, thrombosis, and bleeding. The patient will continue warfarin, and regular replacement therapy with protein C concentrate is also planned. This case highlights the potential benefits of new treatment options for severe PC deficiency and underscores the importance of early and appropriate intervention in managing this rare but potentially life-threatening condition.

This study investigated the increase in blood concentration of methotrexate (MTX) due to delayed elimination when a dipeptidyl peptidase-4 (DPP-4) inhibitors with organic anion transporter 3 (OAT3) inhibitory effects was co-administered with high-dose methotrexate therapy (HD-MTX). During the study period, five patients received a DPP-4 inhibitors. Delayed MTX elimination was confirmed in two of these patients 48 hours after the start of MTX administration. Both patients had received a DPP-4 inhibitors with OAT3 inhibitory effects. Previous literature has reported that MTX elimination may be delayed by the co-administration of drugs that have OAT3 inhibitory effects, but no reports have addressed the impact on actual blood concentration. This study suggests that co-administration of a DPP-4 inhibitors with OAT3 inhibitory effects during HD-MTX may contribute to an increase in blood MTX concentration 48 hours after the start of MTX administration. When conducting HD-MTX therapy, consideration should be given to switching to an alternative treatment.