Search

Abstract Relapsed/refractory acute myeloid leukemia (AML) patients generally have a dismal prognosis and the treatment remains challenging. Due to the expression of CD7 on 30% AML and not on normal myeloid and erythroid cells, CD7 is an attractive target for immunotherapy of AML. CD7-targeted CAR T-cells had demonstrated encouraging efficacy in xenograft models of AML. We report here on the use of autologous CD7 CAR T-cells in the treatment of a relapsed/refractory AML patient with complex karyotype, TP53 deletion, FLT3-ITD mutation, and SKAP2-RUNX1 fusion gene. Before the CAR T-cell therapy, the patient achieved partial remission with IA regimen and attained complete remission after reinduction therapy (decitabine and venentoclax). Relapse occurred after consolidation (CLAG regimen). Then she failed CLIA regimen combined with venetoclax and exhibited resistance to FLT3 inhibitors. Bone marrow showed 20% blasts (CD7+ 95.6%). A total dose of 5 × 106/kg CD7 CAR T-cells was administered after the decitabine +FC regimen. Seventeen days after CAR T-cells infusion, she achieved morphologic leukemia-free state. The patient developed grade 3 cytokine release syndrome. No severe organ toxicity or immune effector cell-associated neurotoxicity syndrome was observed. In summary, the autologous CD7 CAR T-cell therapy could be considered a potential approach for AML with CD7 expression (NCT04762485). Trial registration Clinical Trials.gov, NCT04762485. Registered on February 21, 2021, prospectively registered

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.

Microparticles (MPs) are small membrane vesicles that are classified into subcategories based on their origin, such as platelet-derived MPs (PMPs), endothelial MPs (EMPs), red blood cell MPs (RMPs) and tissue factor MPs (TF + MPs). Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN) are disorders characterized by abnormal haematopoiesis, thrombosis and the JAK2V617F mutation. MPs are biomarkers for procoagulant state in cancer patients, but their relevance in patients with Ph-MPN was unclear. The present study aimed to measure MP variation in MPN patients and evaluate association with the JAK2V617F mutation and with thrombosis and splenomegaly. In total, 92 patients with MPN were enrolled in the present study, including 60 with essential thrombocythaemia (ET), 20 with polycythaemia vera (PV), and 12 with primary myelofibrosis (PMF). RMPs, PMPs, TF + MPs and EMPs were measured by flow cytometry. The levels of RMPs, PMPs, EMPs and TF + MPs in patients with Ph-MPN were all found to be significantly increased compared with controls (P<0.05). Additionally, the levels of all four types of MPs in the PMF group were significantly increased compared with the PV group (P<0.05), and the level of RMPs in the PMF group was significantly increased compared with the ET group (P<0.05). MP levels were increased in the Ph-MPN patients with thrombosis compared with patients without thrombosis (P<0.05). MP levels were increased in Ph-MPN patients with splenomegaly compared with patients without splenomegaly (P<0.05). The level of PMPs in patients with the JAK2V617F mutation was increased compared with patients without the mutation (P<0.05). In conclusion, the present study showed that MPs are associated with Ph-MPN pathogenesis, and may promote thrombosis. [ABSTRACT FROM AUTHOR]