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Patients with Richter's transformation of chronic lymphocytic leukemia (CLL) to diffuse large B‐cell lymphoma (DLBCL‐RT) face a dismal prognosis. A 51‐year‐old female patient diagnosed with CLL with deletion (17p) in 2009. CLL treatment included chemoimmunotherapy and targeted substances. DLBCL‐RT was diagnosed in November 2016. After receiving an allogeneic hematopoietic stem cell transplantation, she relapsed in September 2019 and tisagenlecleucel was infused in December 2019. Cytokine release syndrome grade 2 was treated with two doses of tocilizumab and the patient was started on 140 mg ibrutinib in February 2020. Our patient remains in remission up to 4 years after CAR T‐cell treatment. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T‐cell therapy has become a commercially available treatment option for relapsed or refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) with two or more lines of prior therapies, and recently for high‐risk r/r DLBCL with one prior line of therapy. The successful development of CAR T‐cell therapy for multiple relapsed DLBCL has led to a boom in subsequent trials that investigated its utility in patients with other r/r B‐cell lymphoma subtypes. However, CAR T‐cell therapy is a multistep process that includes leukapheresis and manipulation which take several weeks. Therefore, patients with rapidly progressing or bulky disease may not be able to complete the therapeutic regimen involving CAR T‐cell products. This raises the question of the generalizability of the results of pivotal studies to the entire population. In this review, we summarize the development of CAR‐T cell therapy for B‐cell lymphoma and discuss strategies to further improve the clinical outcomes of this treatment. [ABSTRACT FROM AUTHOR]

Objectives: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)‐T cell therapy. Methods: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non‐severe bleeding group. The thromboelastography data was collected on the day of CAR‐T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR‐T cell infusion. Results: The patients of the severe bleeding group had lower platelet (p <.007), maximum amplitude (p =.002), coagulation index (p =.005), and longer coagulation time (p =.019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0–10, opposite on Days 10–20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR‐T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84–0.95; p <.001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35–5.32; p =.006) were significantly associated with high bleeding severity. Conclusions: Thromboelastography was considered to be a good predictor of bleeding severity. [ABSTRACT FROM AUTHOR]

While cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome are well‐recognized acute toxicities of chimeric antigen receptor (CAR) T cell therapy, these complications have become increasingly manageable by protocolized treatment algorithms incorporating the early administration of tocilizumab and corticosteroids. As CAR‐T cell therapy expands to new disease indications and the number of long‐term survivors steadily increases, there is growing recognition of the need to appropriately evaluate and manage the late effects of CAR‐T cell therapy, including late‐onset or persistent neurotoxicity, prolonged cytopenias, delayed immune reconstitution and infections, subsequent malignancies, organ dysfunction, psychological distress, and fertility implications. In this review, we provide a practical approach to the long‐term survivorship care of the CAR‐T cell recipient, with a focus on the optimal strategies to address the common and challenging late complications affecting this unique population. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effectiveness of donor‐derived chimeric antigen receptor T (CAR‐T) cells in the treatment of relapsed cases after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and whether donor‐derived peripheral blood stem cells (PBSCs) have a therapeutic effect on pancytopenia after CAR‐T cell therapy. Methods: We analyzed data from five adults with B‐cell acute lymphoblastic leukemia (ALL) who had relapse after allo‐HSCT and received donor‐derived CAR‐T cell therapy and donor‐derived PBSCs to promote hematopoietic recovery. Results: All patients had negative minimal residual disease after CAR‐T therapy, grade 1–2 cytokine release syndrome, and developed grade 4 hematologic toxicity. During the pancytopenia stage after CAR‐T cell therapy, donor‐derived PBSCs were transfused without graft‐versus‐host disease (GVHD) prophylaxis. Four patients had grade I–II acute GVHD (aGVHD). After corticosteroid treatment, aGVHD resolved and hematopoiesis was restored. Although steroids in combination with etanercept and ruxolitinib relieved symptoms in one patient with grade IV aGVHD, complete hematopoietic recovery was not achieved, and the patient died due to severe infection. Conclusions: Donor‐derived CAR‐T cell therapy is safe and effective in patients with relapsed/refractory ALL after allo‐HSCT. Donor‐derived PBSCs infusion could achieve hematopoietic recovery with controllable aGVHD in patients with persistent pancytopenia. [ABSTRACT FROM AUTHOR]