Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, so far, no large cohort study determined the risk factors and the most effective therapeutic strategies for TA-TMA. Thus, the present study aimed to clarify these clinical aspects based on a large multicenter cohort. This retrospective cohort study was performed by the Kyoto Stem Cell Transplantation Group (KSCTG). A total of 2425 patients were enrolled from 14 institutions. All patients were aged ≥16 years, presented with hematological diseases, and received allo-HSCT after the year 2000. TA-TMA was observed in 121 patients (5.0%) on day 35 (median) and was clearly correlated with inferior overall survival (OS) (hazard ratio [HR], 4.93). Pre- and post-HSCT statistically significant risk factors identified by multivariate analyses included poorer performance status (HR, 1.69), HLA mismatch (HR, 2.17), acute graft-versus-host disease (aGVHD; grades 3-4) (HR, 4.02), Aspergillus infection (HR, 2.29), and veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS; HR, 4.47). The response rate and OS significantly better with the continuation or careful reduction of calcineurin inhibitors (CNI) than the conventional treatment strategy of switching from CNI to corticosteroids (response rate, 64.7% vs 20.0%). In summary, we identified the risk factors and the most appropriate therapeutic strategies for TA-TMA. The described treatment strategy could improve the outcomes of patients with TA-TMA in the future.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases with variable outcomes. Although several prognostic markers have been developed, specific biomarkers for stratifying treatment strategies have not been fully investigated. This study aimed to analyze the clinical impact of the expression of cluster of differentiation (CD) 38, which is associated with cellular proliferation and disease progression, in patients with de-novo DLBCL. Using flow cytometry analysis, 137 cases with DLBCL were investigated for surface expression of CD38. Based on the cut-off value by the survival classification and regression tree analysis, the patients were categorized into a CD38 HIGH group (n = 37) and CD38 LOW group (n = 100).The 4-years progression-free survival (PFS) was 31.6% in the CD38 HIGH group and 60.7% in the CD38 LOW group (p < 0.001). Multivariate analysis showed the CD38 HIGH group to be associated with significantly worse PFS (adjusted hazard ratio [aHR], 2.15, 95% CI: 1.26-3.68, p = 0.005) and poor overall survival (OS) (aHR, 2.54, 95% CI: 1.25-5.19, p = 0.010) than the CD38 LOW group. In conclusion, we demonstrated that high CD38 expression is an independent adverse prognostic factor associated with poor clinical outcomes compared to low CD38 expression. CD38 expression in DLBCL cells might be useful for predicting outcomes and designing risk-adapted therapies for patients with de-novo DLBCL. K E Y W O R D Sdiffuse large B-cell lymphoma, CD38, progression free survival | INTRODUCTIONDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma. Chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) leads to cure in approximately 50% to 60% of patients. However, one-third of patients develop relapse or refractory disease, and have particularly poor outcomes. DLBCL represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical manifestations, cell of origin (COO), molecular features, and frequently recurring mutations. 1,2 Owing to the heterogeneity, several prognostic models and/or various prognostic markers have been developed or assessed to predict survival. For example, the clinical prognostic stratification model, international prognostic index (IPI), is a powerful tool for predicting the survival of patients with DLBCL. However, these

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Background Cold agglutinin syndrome (CAS) is associated with various diseases. Several studies of CAS associated with coronavirus disease 2019 (COVID‐19) reported hemolytic anemia and thrombosis; however, the clinical significance of cold agglutinins (CA) in patients with COVID‐19 is unclear. Here, we present two cases of CA identified in the context of COVID‐19 without hemolytic anemia and clotting. Case report and Discussion Two patients with no known risk factors for CA were diagnosed with COVID‐19; peripheral blood smears reveal red blood cells (RBCs) agglutination. These patients showed a high CA titer. We confirmed retrospectively that the CA was an anti‐I antibody. The two COVID‐19 cases with a high CA titer showed no hemolysis or thrombosis. Mycoplasma pneumoniae is known to cause CAS, but not all patients who have a high CA titer show hemolysis. Coagulation abnormalities are documented in severe COVID‐19 cases. Although CA increases the risk of thrombosis in those with lymphoproliferative diseases, the role of anti‐I antibodies in COVID‐19 is unclear. The impact of CAS on clinical presentations in COVID‐19 remains a matter of verification. Conclusions A high CA titer was identified in COVID‐19 patients without hemolytic anemia and clotting. Anti‐I antibodies were identified. Further studies are required to clarify the pathophysiology of CA in COVID‐19.

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The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients. This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination. A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The median anti-S1 IgG titers were 395 and 499 BAU/mL in patients and healthy controls, respectively (p = 0.606). A short time interval between transplantation and vaccination (≤ 6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded. Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.