Objective:To investigate the efficacy and safety of sequential therapy of targeting CD19 and CD22 chimeric antigen receptor T-cell (CAR-T) following autologous stem cell transplantation (ASCT) in treatment of renal diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence.Methods:The clinical data of 1 renal DLBCL patient with CNS recurrence admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology in May 2019 were retrospectively analyzed. The patient received sequential therapy of targeting CD19 and CD22 CAR-T following ASCT. The relative indicators of the primary disease remission at 1, 3, 6, 12, 18 and 24 months after therapy were analyzed, and relevant literature was reviewed.Results:The male patient aged 23 years had CNS recurrence after 8 courses of R-CHOP chemotherapy and then he received sequential therapy of targeting CD19 and CD22 CAR-T following ASCT. During the process of treatment, this patient developed grade 1 cytokine release syndrome and his condition was well controlled after active treatment. The white blood cell and platetes were successfully implanted. CNS symptoms along with immature cells in cerebrospinal fluid disappeared completely. Liquid biopsy was used to dynamically monitor the residue disease of the patient and the duration of remission period lasted 26 months. This patient developed tuberculosis one year after treatment and recovered from anti-tuberculosis agents.Conclusions:Sequential therapy of targeting CD19 and CD22 CAR-T following ASCT provides a novel therapeutic approach for renal DLBCL with CNS recurrence. Especially for patients who are neither sensitive to conventional chemotherapy nor CAR-T therapy alone, this regimen may improve remission rate and survival.

Objective:To explore the risk factors and outcomes of central nervous system(CNS)complications associated with hematopoietic stem cell transplantation(HSCT).Methods:A total of 550 recipient after HSCT in the department of hematology of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1 2019 to August 31 2021were enrolled.According to the occurrence of CNS complications, they were divided into the CNS group(24 cases)and the non CNS group(526 cases). The clinical information and prognosis were compared.We further analyzed the risk factors associated with CNS complications, and conducted multivariate logistic regression on statistically significant indicators.Cox regression analysis is conducted on prognostic factors such as age, gender and risk degree.Results:A total of 550 recipients were enrolled, of which 330 underwent allo-HSCT, and others received auto-HSCT.A total of 24 cases (4.36%)had CNS complications, of which 4 cases had 2 types of CNS complications.The type of CNS complications included intracranial infection(8 cases, 28.57%), transplantation-associated thrombotic microangiopathy(TA-TMA)(6 cases, 21.43%), central tumor invasion(4 cases, 14.29%), intracranial hemorrhage(4 cases, 14.29%), leucodystrophy(2 cases, 7.14%)and unexplained encephalopathy(4 cases, 14.29%). Logistic regression analysis of risk factors related to CNS complications showed that, Platelet implantation time( β=0.084, OR=1.088, P=0.048), CMV infection( β=1.295, OR=3.65, P=0.008)is positively correlated with the occurrence of CNS complications in HSCT recipients but age( β=-0.052, OR=0.949, P=0.004)is negatively correlated with it.Nine of the 24 cases(37.50%)who experienced CNS complications died, including 3 cases of intracranial infection, 3 cases of cerebral hemorrhage, 2 cases of TMA, and 1 case of unexplained encephalopathy.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients. Conclusions:Our results indicated that, age, CMV infection and platelet implantation time were associated with the occurrence of CNS complications after HSCT.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.