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Summary: Reduced‐intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non‐Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced‐dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low‐dose melphalan (80 or 100 mg/m2; Flu/Mel80–100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end‐point was the 5‐year overall survival (OS). The 5‐year OS was 53.8% (95% CI, 47.6–59.6) and 42.4% (95% CI, 35.6–49.0) in the Flu/Bu2 and Flu/Mel80–100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80–100 group for 5‐year OS was 0.77 (95% CI, 0.60–0.99, p = 0.046), 0.97 (95% CI, 0.78–1.21, p = 0.798) for 5‐year progression‐free survival, 0.65 (95% CI, 0.45–0.94, p = 0.022) for 5‐year cumulative risk of non‐relapse mortality and 1.25 (95% CI, 0.95–1.64, p = 0.115) for 5‐year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non‐relapse mortality than those who received Flu/Mel80–100. [ABSTRACT FROM AUTHOR]

Background: The tumour microenvironment (TME), which is modulated after immune‐chemotherapy, is involved in tumour growth and metastasis. Programmed cell death 1 (PD‐1) expressed on tumour‐infiltrating non‐malignant cells plays an important role in the TME through the PD‐1/programmed cell death ligand 1 (PD‐L1) signalling pathway. However, its impact in patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) remains unclear. Methods: We conducted a retrospective study using tissue samples at relapse for patients with R/R DLBCL (n = 45) and evaluated the clinical impact of PD‐1 expression on tumour‐infiltrating non‐malignant cells (microenvironmental PD‐1, mPD‐1). In addition, corresponding 27 samples at diagnosis were analysed to evaluate the changes in PD‐1/PD‐L1 expression in the TME after chemotherapy. Results: Patients with mPD‐1+ DLBCL showed significantly better overall survival compared with patients with mPD‐1− DLBCL (hazard ratio, 0.30, p = 0.03). Among patients with mPD‐1− DLBCL, those positive for neoplastic or microenvironmental PD‐L1 (nPD‐L1+ or mPD‐L1+) showed significantly worse outcomes. Microenvironmental PD‐1 and PD‐L1 expression has high correlation at relapse, although none was found at diagnosis. Conclusion: We determined the clinical impact of microenvironmental PD‐1 expression and its relationship with neoplastic or microenvironmental expression of PD‐L1 in patients with R/R DLBCL. The expression of PD‐1 and PD‐L1 in the TME dramatically changes during the chemotherapy. Therefore, evaluating TME at relapse, not at diagnosis is useful to predict the outcomes of R/R DLBCL patients. [ABSTRACT FROM AUTHOR]

A 43-year-old man with pancytopenia was diagnosed with acute promyelocytic leukemia (APL). On the first day of induction therapy with all-trans retinoic acid (ATRA) alone, he presented with high fever and was found to have coronavirus disease 2019 (COVID-19) infection by SARS-CoV2 antigen test. While it is generally recommended to delay treatment for APL patients with COVID-19 unless urgent APL treatment is required, this patient needed to continue treatment due to APL-induced disseminated intravascular coagulation (DIC). Considering the challenge of distinguishing between differentiation syndrome (DS) and COVID-19 exacerbation, the ATRA dosage was reduced to 50%. The patient was able to continue treatment without development of DS or exacerbation of DIC, leading to his recovery from COVID-19 and remission of APL.

A 93-year-old woman was diagnosed with lymphoplasmacytic lymphoma (LPL) with circulating tumor cells in her peripheral blood after presenting with anemia. LPL progressed eight months later, with anemia worsening and tumor cells increasing to 66% of leukocytes. She began tirabrutinib at a low dose (80 mg daily: 17% of the standard dose) because she preferred to maintain her quality of life (QOL). Within three weeks, she was free of transfusion dependency and had a partial response with the disappearance of peripheral tumor cells. The dosage of tirabrutinib was increased to 240 mg daily because it was well tolerated. She has been on the treatment for 13 months with no adverse effects. Tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, has been reported to have promising efficacy for LPL, but it also has a high incidence of dermatological toxicity, which may impair QOL. Low-dose tirabrutinib initiation may be effective and assist elderly patients with LPL in maintaining their QOL.

A 68-year-old man was referred to our hospital with dizziness and mild fever one week after receiving the second dose of the COVID-19 mRNA vaccine (BNT162b2). Laboratory tests showed hemolytic anemia and a positive direct Coombs test, and he was diagnosed with autoimmune hemolytic anemia (AIHA). On admission, the patient had impaired consciousness with auditory hallucinations, and a head MRI scan showed multiple high-signal areas on diffusion-weighted imaging, suggesting multiple recent infarctions. Echocardiography also showed decreased wall motion in the inferior and posterior walls. A skin biopsy to investigate the cause revealed many platelets and fibrin thrombi in the capillaries and small veins, which was considered the cause of the organ damage. After starting prednisolone (1 mg/kg) for AIHA, hemolytic anemia as well as impaired consciousness, and decreased wall motion rapidly improved. Microthrombosis after BNT162b2 mRNA vaccination is rare, and autoimmune abnormalities appeared to contribute to onset in this case.