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FOURTH GENERATION HUCART19-IL18 PRODUCES DURABLE RESPONSES IN LYMPHOMA PATIENTS PREVIOUSLY RELAPSED/REFRACTORY TO ANTI-CD19 CAR T-CELL THERAPY B Introduction: b Lymphoma (NHL) patients (pts) relapsing/refractory (R/R) to anti-CD19 chimeric antigen receptor T-cells (CART) represent a challenging group in need of effective therapies. B Conclusions: b HuCART19-IL18 therapy results in durable responses in pts with CD19+ NHL who are R/R to prior 2 SP nd sp generation anti-CD19 CART. [Extracted from the article]

B Conclusions: b In cHL patients R/R to BV and CPIs, the combination of everolimus and itacitinib was well tolerated and produced high response rates that compare favorably to historical reports of mTOR or JAK inhibitors as monotherapies. B Introduction: b Patients (pts) with classic Hodgkin lymphoma (cHL) who have failed or are intolerant of BV and CPI have few available treatment options. [Extracted from the article]

14/16 (88%) patients developed CRS; 11/14 (79%) had grade 1-2 CRS and 3 (19%) had grade 3 or greater CRS. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT consensus criteria. 5 (31%) patients had ICANS; 2 (12.5%) had grade 1-2 ICANS, and 3 (19%) had grade 3 or greater ICANS. [Extracted from the article]

B Introduction: b Despite recent successes with CAR T-cell therapy against CD19 in patients with B-celllymphomas, only ~30%-40% of DLBCL and FL patients maintain a durable complete long-term remission, and over half of the patients will ultimately relapse. To investigate CAR T-cell-mediated tumor killing in human cells in combination with EZH2i tazemetostat, we used the GCB-DLBCL cell lines SUDHL4 (EZH2 SP Y641F sp ), OCI-Ly18 and Toledo (WT EZH2). [Extracted from the article]

Patients with chemo-refractory acute myeloid leukemia (AML) have a dismal prognosis. Chimeric antigen receptor T (CART) cell therapy has produced exciting results in CD19+ malignancies and may overcome many of the limitations of conventional leukemia therapies. We developed CART cells to target CD33 (CART33) using the anti-CD33 single chain variable fragment used in gemtuzumab ozogamicin (clone My96) and tested the activity and toxicity of these cells. CART33 exhibited significant effector functions in vitro and resulted in eradication of leukemia and prolonged survival in AML xenografts. CART33 also resulted in human lineage cytopenias and reduction of myeloid progenitors in xenograft models of hematopoietic toxicity, suggesting that permanently expressed CD33-specific CART cells would have unacceptable toxicity. To enhance the viability of CART33 as an option for AML, we designed a transiently expressed mRNA anti-CD33 CAR. Gene transfer was carried out by electroporation into T cells and resulted in high-level expression with potent but self-limited activity against AML. Thus our preclinical studies show potent activity of CART33 and indicate that transient expression of anti-CD33 CAR by RNA modification could be used in patients to avoid long-term myelosuppression. CART33 therapy could be used alone or as part of a preparative regimen prior to allogeneic transplantation in refractory AML. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate granulocyte colony-stimulating factor (G-CSF) efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy for genu varum. Methods: A phase II trial was conducted for evaluating the preoperative administration of G-CSF given at 10 μg/kg/day for 3 consecutive days with an additional half-dose 4 h before the opening-wedge high tibial valgus osteotomy. Overall, 12 patients (Group A) received G-CSF treatment, and the subsequent 12 patients (Group B) underwent surgery without G-CSF. The osteotomy gap was filled by a bone graft substitute. Bone marrow cell (BMC) mobilization was monitored by CD34+ve cell and clonogenic progenitor cell analysis. All patients underwent a clinical (Lysholm Knee Scale and SF-36) and radiographic evaluation preoperatively, as well as at given intervals postsurgery. Results: All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC mobilization occurred in all Group A patients, with median peak values of circulating CD34+ve cells of 110/μL (range 29-256). Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in Lysholm Knee Scale was recorded at follow-up in Group A compared to Group B. At the radiographic evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months postsurgery compared to Group B. The computerized tomography scan of the grafted area at 2 months postsurgery showed no significant difference in the quality of the newly formed bone between the two Groups. Conclusions: Although the limited number of patients does not allow firm conclusions, the study suggests that G-CSF can be safely administered preoperatively in subjects undergoing opening-wedge high tibial valgus osteotomy; in addition, the clinical, radiographic and CT monitoring indicate that G-CSF and/or mobilized BMCs may hasten bone graft substitute osseointegration. Level of evidence: I. [ABSTRACT FROM AUTHOR]

Our objective was to characterize the role of grafted cells in determining telomere length (TL) after hematopoietic SCT (HSCT). A total of 20 patients undergoing autografts had PBSC collected after two sequential mobilization courses: TL in the first collection was significantly longer than in the second. For their autografts, 10 patients used PBSC from the first collection and 10 from the second. TL was also investigated before and after HSCT and on the graft in 10 allogeneic HSCT. After autografting, patients receiving PBSC from the first collection had BM TL reflecting that of grafted cells (median bp: 7730 on PBSC vs 7610 on post-HSCT BM, P=NS) and significantly longer than TL of the second collection; analogously, patients autografted with PBSC from the second collection had BM TL reflecting that of grafted cells (7360 on PBSC vs 7120 on post-HSCT BM, P=NS) and significantly shorter compared with the first collection. In the allograft setting, eight patients had their pre-transplant TL significantly shorter than donor PBSC (5960 vs 7110; P=0.0005); following HSCT, BM TL (median 7380 bp) was identical to that of the graft (P=NS). We conclude that grafted cells have a major role in determining TL after HSCT. [ABSTRACT FROM AUTHOR]