Search

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]

Blinatumomab is a bispecific T cell‐engaging antibody approved for treatment of relapsed/refractory (r/r) ALL, with 40%‐50% complete response (CR)/CR with incomplete count recovery (CRi). Cytokine release syndrome (CRS) as a major adverse effect after blinatumomab therapy. Here, we evaluated the possible association between single‐nucleotide polymorphisms (SNPs) in cytokine genes, disease response, and CRS in r/r ALL patients who received blinatumomab between 2012 and 2017 at our center (n = 66), using patients' archived DNA samples. With a median duration of 9.5 months (range: 1‐37), 37 patients (56.1%) achieved CR/CRi, 54 (81.8%) experienced CRS (G1: n = 35, G2: n = 14, G3: n = 5), and 9 (13.6%) developed neurotoxicity. By multivariable analysis, after adjusting for high disease burden, one SNP on IL2 (rs2069762), odds ratio (OR) = 0.074 (95% CI: NE‐0.43, P =.01) and one SNP on IL17A (rs4711998), OR = 0.28 (95% CI: 0.078‐0.92, P =.034) were independently associated with CR/CRi. None of the analyzed SNPs were associated with CRS. To our knowledge, this is the first study demonstrating a possible association between treatment response to blinatumomab and SNPs. Our hypothesis‐generated data suggest a potential role for IL‐17 and IL‐2 in blinatumomab response and justify a larger confirmatory study, which may lead to personalized blinatumomab immunotherapy for B‐ALL. [ABSTRACT FROM AUTHOR]