Prediction of responses to chimeric antigen receptor (CAR)-T cell therapies is essential to maximize their therapeutic efficacy for diffuse large B-cell lymphoma (DLBCL). While several tumor-intrinsic risk factors of resistance and/or early relapse have been identified, clinically useful markers that determine potential activity of CAR-T cells have not been fully investigated. T-cell property at the time of leukapheresis may serve as such a marker. Therefore, we evaluated the clinical impact of CD3+ cell count in peripheral blood at leukapheresis on clinical outcomes of CAR-T cell therapy. In total, 44 patients with relapsed or refractory (r/r) DLBCL who received tisagenlecleucel at Kyoto University Hospital were included. According to CD3+ cell counts, patients were categorized into CD3LOW and CD3HIGH groups with a threshold of 553/μL, based on receiver operating characteristic curve analysis. 1-year progression-free survival was significantly higher in the CD3HIGH group than the CD3LOW group (68.3% vs. 17.3%; adjusted hazard ratio [aHR], 0.37; p = 0.042). Overall survival was also superior in the CD3HIGH group (aHR, 0.24; p = 0.043). Moreover, higher CD3+ cell counts at leukapheresis were associated with significantly higher lymphocyte counts in peripheral blood at day 7 after CAR-T cell infusion (median 860 vs. 420/μL, P = 0.021), suggesting more extensive expansion of infused CAR-T cells in vivo. In conclusion, we demonstrated that the CD3+ cell count at leukapheresis predicts both expansion of CAR-T cells after infusion and outcomes of CAR-T cell therapy, and are useful for building comprehensive therapeutic strategies at the time of leukapheresis.
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
Background. Unrelated cord blood (UCB) and haploidentical related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) have become alternative options to treat patients with hematological malignancies without a HLA-matched donor. Methods. We conducted a retrospective study using registry data from the Kyoto Stem Cell Transplantation Group for patients with hematological malignancies who received their first allogeneic hematopoietic cell transplantation using a single UCB unit (n = 460) or PTCy-haplo (N = 57) between 2013 and 2019. Results. We found that overall survival in the UCB group was comparable to that in the PTCy-haplo group (hazard ratio, 1.00; 95% confidence interval, 0.66-1.52), although neutrophil and platelet engraftment were significantly delayed. Nonrelapse mortality risk and the incidence of graft-versus-host disease in the UCB group were also comparable to those in the PTCy-haplo group. Although the relapse risk was similar between the UCB group and the PTCy-haplo group regardless of the disease risk, acute myeloid leukemia patients benefit from UCB transplant with a significantly lower relapse rate (hazard ratio, 0.38; 95% confidence interval, 0.18-0.76). Conclusions. UCB transplant gives outcomes comparable to PTCy-haplo transplant, and both UCB and PTCy-haplo units are suitable as alternative donor sources for patients without an HLA-matched sibling or unrelated donor.
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