[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies.

A comparison was conducted of 213 patients with haematologic malignancies who underwent HLA-identical sibling (n=108) or HLA-haploidentical (n=105) haematopoietic cell transplantation (haplo-HCT) at our centre. The conditioning regimen included fludarabine, busulphan, cyclophosphamide and antilymphocyte globulin (ATG) (FBCA). The total dose of ATG differed between identical and haploidentical groups (3.75 mg/kg versus 12.5 mg/kg). The cumulative incidences of grade II-IV acute GvHD in the identical and haploidentical groups were 20.4% and 21.9% (P=0.73), and 2-year cumulative incidences of chronic GvHD were 36.4% and 24.1% (P=0.17), respectively. The 3-year probabilities of non-relapse mortality for identical and haploidentical groups were 20.5% and 34.9% (P=0.048), and for relapse were 22.2% and 21.0% (P=0.85), respectively. The 3-year overall survivals in the identical and haploidentical groups were 62.6% and 52.6% (P=0.054), whereas the 3-year disease-free survivals were 54.7% and 43.1% (P=0.14), respectively. In the multivariate analysis, patients in the high-risk group exhibited reduced survival, and the higher dose of mononuclear or CD34+ cells resulted in an increase in the likelihood of survival. In conclusion, haplo-HCT based on an FBCA conditioning regimen could achieve nearly comparable outcomes to HLA-identical sibling HCT.

Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an alternative for patients who need a transplant without having conventional donors. One hundred and five consecutive patients with hematologic malignancies who underwent G-CSF-primed peripheral blood haplo-HSCT without in vitro T-cell depletion in our single center were reported in this study. Patients were categorized into the intermediate-risk group (n=28) or high-risk group (n=77) according to the risk stratification. The conditioning regimen included fludarabine, busulfan, cyclophosphamide and anti-lymphocyte globulin. The cumulative incidence of grades II-IV acute GvHD (aGvHD) on day +100 was 21.9%, and that of grades III-IV aGvHD was 14.3%. The 2-year cumulative incidence of total chronic GvHD (cGvHD) was 24.1%, and that of extensive cGvHD was 5.6% in 83 eligible patients. The 3-year cumulative incidence rates of relapse and no relapse mortality were 21.9% and 30.5%, respectively. After a median follow-up of 35 months, the 3-year probabilities of overall and disease-free survival for the intermediate-risk and high-risk groups were 63.2% and 39.8% and 61.2% and 32.2%, respectively. In multivariate analysis, the outcome of survival (overall survival and disease-free survival) was associated with the risk stratification, disease status at transplant and dose of infused mononuclear cells. Our results suggest that unmanipulated peripheral blood stem cell allograft performed with fludarabine, busulfan, cyclophosphamide and anti-lymphocyte globulin conditioning regimen is feasible.

In vitro cellular response of retinoic acid treated human oral cancer cell lines.

BACKGROUND: The purpose of this study is to identify the cellular response ofretinoic acid-treated human oral cancer cell lines. METHODS: Seven human oral cancer cell lines KB, SCC4, SCC9, SCC15, SCC25, OEC-M1, OC1 and OC2 were used for cell culture experiments. Direct cell number counting method was utilized to evaluate cellular response of these human oral cancer cells at the presence or absence of all-trans RA at 1 mM. RESULTS: Through 7-day observation, the cell population of SCC9, SCC15 and SCC25 of RA-treated groups decreased when compared with the non RA-treated groups. These three cell lines were further verified using [3H] thymidine incorporation DNA synthesis assay. KB, SCC4, OC1, OC2 and OEC-M1 cell lines did not show growth inhibition at the presence of RA at 1 mM. CONCLUSIONS: The molecular event of how SCC9, SCC15 and SCC25 are inhibited by RA and how KB, OC1, OC2 and OECM1 are resistant to RA can be further explored on the basis of this study.