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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]

Background: Cytomegalovirus reactivation (CMV-R) is a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HCT), especially in human leukocyte antigen-haploidentical transplantation (haplo-HCT) with posttransplant cyclophosphamide (PTCy). Prophylactic letermovir (LTV) prevents CMV-R in patients undergoing allo-HCT. However, evidence regarding its use in haplo-HCTs with PTCy is limited. Therefore, we aimed to investigate the efficacy of prophylactic LTV in haplo-HCT with PTCy. Methods: We retrospectively analyzed 52 patients seropositive for CMV who underwent haplo-HCT with PTCy at our institution between January 2015 and June 2021 and compared patients who received LTV prophylaxis (LTV group: n = 29) with those who did not receive prophylaxis for CMV (control group: n = 23). The primary endpoint was the 100-day cumulative CMV-R incidence. We used Gray's test and the Fine and Gray test to compare the two groups. Results: The 100-day cumulative CMV-R incidence was lower in the LTV group than in the control group (17.2% vs 81.8%, p < 0.001). Multivariate analysis revealed that prophylactic LTV reduced the 100-day cumulative CMV-R incidence (hazard ratio: 0.17, 95% confidence interval: 0.06–0.44, p < 0.001). Conclusions: Prophylactic LTV effectively prevents CMV-R in patients undergoing haplo-HCT for PTCy. [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]

Allogeneic hematopoietic cell transplantation (HCT) offers a possible cure for patients with relapsed and refractory non-Hodgkin lymphoma (NHL) through potentially beneficial graft versus lymphoma effects. However, allogeneic HCT is associated with high nonrelapse mortality (NRM). Fludarabine with reduced-intensity busulfan (Flu/Bu2) and myeloablative busulfan (Flu/Bu4) are commonly used in conditioning regimens for allogeneic HCT; however, data on their use in patients with NHL is limited. We investigated the effect of busulfan dose on outcomes by comparing Flu/Bu2 and Flu/Bu4 in patients with NHL who underwent allogeneic HCT. Our study included 415 adult patients with NHL who received Flu/Bu2 (315 patients) or Flu/Bu4 (100 patients) between January 2008 and December 2019. All patients were enrolled in the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. The primary endpoint was the 5-year overall survival (OS). To minimize potential confounding factors that may influence outcomes, we performed propensity score matching. The 5-year OS was 50.6% (95% confidence interval (CI), 39.4%–60.8%) and 32.2% (95% CI, 22.4–42.4%) in the Flu/Bu2 and Flu/Bu4 groups, respectively (p = 0.006). The hazard ratio comparing the two groups was 2.13 (95% CI, 1.30–3.50; p = 0.003). Both groups had a similar 5-year cumulative incidence of relapse (38.2% vs 41.3%; p = 0.581), and the Flu/Bu4 group had a higher cumulative incidence of 5-year NRM (15.7% vs 31.9%; p = 0.043). In this study, Flu/Bu4 was associated with worse OS compared with Flu/Bu2 because of high NRM in patients with NHL. [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]

Patients with hematologic diseases receiving anti-CD20 monoclonal antibodies show a low seroconversion rate after two doses of mRNA Coronavirus disease-2019 (COVID-19) vaccines, especially within 12 months of their last anti-CD20 antibodies [[1]]. In total, while either humoral or cellular responses were identified in 22 (42%) patients after two doses of the vaccine, a third vaccination induced them in 36 (72%) patients (Fig. Ten patients were excluded from the final analysis: four patients were infected with SARS-CoV-2 before the completion of blood sampling, two patients had undocumented COVID-19 infection, two did not have blood sampling before the third vaccination, and two did not receive their third dose. [Extracted from the article]

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]