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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]

Objectives: The higher risk of prolonged viral shedding in coronavirus disease (COVID‐19) patients with hematological malignancies (HM) necessitates test‐based de‐isolation strategies. However, evidence to establish their appropriate isolation period is insufficient. This study investigated the factors affecting prolonged viral shedding and the requisite isolation period in these patients. Methods: We retrospectively reviewed 14 COVID‐19 patients with HM between January and April 2022, who were subjected to our test‐based de‐isolation strategy, followed by analysis of the viral load trajectory. The viral loads of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) were evaluated using the cycle threshold (Ct) of the reverse‐transcription quantitative polymerase chain reaction. The trajectories were classified according to the time‐interval from COVID‐19 onset to the attainment of Ct values >30. Results: The median interval between onset and attainment of a Ct value >30 was 22 days. Five patients with mild or moderate COVID‐19 without intense treatment histories achieved Ct values >30 within 20 days. The other nine patients needed more than 20 days, including three patients who did not meet this criterion during the observation period. Conclusions: The SARS‐CoV‐2 viral load trajectories in patients with HM can be stratified by treatment history for the underlying HM and severity of COVID‐19. [ABSTRACT FROM AUTHOR]

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms. [ABSTRACT FROM AUTHOR]

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in patients with haematological diseases treated with anti-CD20 antibodies: An observational study Keywords: BNT162b2; COVID-19; haematological disorders; mRNA-1273; obinutuzumab; rituximab EN BNT162b2 COVID-19 haematological disorders mRNA-1273 obinutuzumab rituximab 709 713 5 06/14/22 20220615 NES 220615 In clinical trials, mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown remarkable efficacy and safety in healthy participants.1,2 However, patients receiving anti-CD20 antibodies, such as rituximab or obinutuzumab (R/Obi), have been shown to have a poor humoral response to mRNA vaccines, although the response improves gradually if more time has elapsed.3,4 R/Obi exerts an immunosuppressive effect through B-cell depletion, which could explain the impaired response to mRNA vaccines. Probability p < 0.001 was calculated using either the Mann-Whitney U test or the chi-squared test. (B) Anti-S1 antibody titre in patients ordered in subgroups according to time from last anti-CD20 antibody treatment to vaccination and B-cell fraction. [Extracted from the article]

Despite progress in the treatment of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), relapsed or refractory DLBCL (rrDLBCL) and FL transformation (tFL) still show dismal prognoses [[1]]. We previously demonstrated that high CD38 expression in patients with I de novo i DLBCL is an independent adverse prognostic factor associated with poor clinical outcomes compared with low CD38 expression [[4]]. The mean fluorescence intensity ratio (rMFI) for CD38 was calculated as the ratio of CD38 fluorescence intensity to the auto-fluorescence of lymphoma cells. [Extracted from the article]

Here, we present a rare case of tyrosine kinase inhibitor (TKI)-induced bone marrow aplasia. A 58-year-old man presented with leukocytosis and was diagnosed with chronic myeloid leukemia. He was initially treated with imatinib for 6 years and abruptly discontinued treatment by himself. He was administered dasatinib 5 years after treatment interruption, and presented with pancytopenia 6 months after dasatinib initiation. Bone marrow biopsy revealed severe hypocellularity without blasts. Dasatinib was discontinued, and he recovered from pancytopenia 3 months later; however, BCR-ABL1 was positive for almost all white blood cells in the peripheral blood. We retreated with ponatinib, but pancytopenia developed again. The clinical course indicated TKI-induced bone marrow aplasia. Therefore, ponatinib was discontinued and the patient received an allogeneic hematopoietic stem cell transplantation from a haploidentical daughter using post-transplant cyclophosphamide. He had a major molecular response and had normal complete blood counts and bone marrow 1 year after transplantation. [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.