1.Sequential cytokine induced killer cells therapy for acute myeloid leukemia after autologous peripheral blood stem cell transplantation
Dingming WAN ; Li LI ; Xinsheng XIE ; Ling SUN ; Hui SUN ; Zhongxing JIANG ; Yi ZHANG ; Weijie CAO ; Zhilei BIAN ; Xuefang ZHOU
Chinese Journal of Tissue Engineering Research 2013;(49):8551-8556
BACKGROUND:Cytokine induced kil er cells therapy as an effective means of adoptive immunotherapy, becomes a new way to treat acute myeloid leukemia. But, the researches about sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation in acute myeloid leukemia patients are stil less, which deserve further research.
OBJECTIVE:To observe the clinical efficiency and safety of sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation in acute myeloid leukemia M2 patients.
METHODS:Total y 45 patients with low-or intermediate-risk acute myeloid leukemia M2 were recruited in this study. Among them, 19 patients received sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation and 26 patients only received autologous peripheral blood stem celltransplantation. The relapse rate, disease-free survival, and overal survival were compared between two groups, and safety of cytokine induced kil er cells therapy was observed.
RESULTS AND CONCLUSION:(1) Compared with the patients only receiving autologous peripheral blood stem celltransplantation, the relapse rate was lower (21.05%vs. 38.46%;P<0.05), and elevated percentages of the disease-free survival and overal survival were observed in the patients receiving sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation (P<0.05). (2) The 19 patients who received sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation al completed the treatment scheme successful y. Only four patients appeared to have chil s and fever, and no more side effects were observed. These findings suggested that the sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation can improve the disease-free survival and overal survival of low-or intermediate-risk acute myeloid leukemia M2 patients without remarkable side effects, which is a safe, effective and feasible way for the treatment of acute myeloid leukemia M2.
2.Analysis of risk factors for short-term death after allogeneic hematopoietic stem cell transplantation
Siyu GAO ; Lihong YAO ; Zhilei BIAN ; Suping ZHANG ; Li LI ; Jinpeng FAN ; Jing QIN ; Yingnan PENG ; Dingming WAN
Chinese Journal of Tissue Engineering Research 2024;28(13):2009-2016
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an effective and even the only way to cure various hematological diseases,but the short-term mortality rate is relatively high after transplantation. OBJECTIVE:To investigate the risk factors affecting the overall survival of patients with hematological diseases in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation,so as to reduce mortality and effectively prevent related risks in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation. METHODS:Clinical data of 585 patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation at the Hematopoietic Stem Cell Transplantation Center of First Affiliated Hospital of Zhengzhou University from January 1,2018 to June 30,2021 were retrospectively analyzed.The risk factors that affected overall survival within 100 days after allogeneic hematopoietic stem cell transplantation were explored. RESULTS AND CONCLUSION:A total of 585 patients with hematologic diseases underwent allogeneic hematopoietic stem cell transplantation.92 patients died within 100 days after transplantation,with a mortality rate of 15.7%(92/585).The median age of death cases was 26.5 years old(1-56 years),and the median survival time of death cases was 48 days(0-97 days).Univariate analysis exhibited that age≥14 years old,acute graft-versus-host disease,grade IV acute graft-versus-host disease,bacterial bloodstream infection,as well as carbapenem-resistant organism bloodstream infection,were risk factors for overall survival within 100 days after allogeneic hematopoietic stem cell transplantation(P<0.05).Multivariate regression analysis showed that age≥14 years old,grades Ⅲ-Ⅳ acute graft-versus-host disease,bacterial bloodstream infection,and carbapenem-resistant organism bloodstream infections were independent risk factors for overall survival(within 100 days)in patients after allogeneic hematopoietic stem cell transplantation.Hazard ratios were 1.77(95%CI 1.047-2.991),7.926(95%CI 3.763-16.695),2.039(95%CI 1.117-3.722),and 3.389(95%CI 1.563-7.347),respectively.In conclusion,all-cause mortality rate after allogeneic hematopoietic stem cell transplantation is relatively high in the short term.A timely diagnosis and effective treatment of bacterial bloodstream infection and acute graft-versus-host disease are essential to improving allogeneic hematopoietic stem cell transplantation outcomes.
3.Comparison of immune reconstitution at early stage after unmanipulated haploidentical stem cell transplantation between high-and standard-risk Philadelphia chromosome-negative acute lymphoblastic leukemia patients in CR1
Zhilei BIAN ; Yingjun CHANG ; Lanping XU ; Yu WANG ; Xiaohui ZHANG ; Kaiyan LIU ; Xiaojun HUANG
Chinese Journal of Hematology 2016;37(8):650-655
Objective To compare the early stage immune reconstitution of high-and standardrisk Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) CR1 patients who had haploidentical blood and marrow stem cell transplantation (HBMT).Methods A total of 49 Ph-negative ALL CR1 patients who received HBMT and had complete early stage immune reconstitution data(+30,+60 and +90 d post transplantation) from Jan.2010 to Dec.2012 were enrolled.Immunophenotyping for B and T lymphocytes was performed post HBMT via flow cytometry.Fresh peripheral blood cells were stained with fluorochrome-labeled monoclonal antibodies against cluster of differentiation CD19,CD3,CD4,CD8,CD45RO,CD45RA and CD28.The early reconstitution of lymphocyte subsets,survival and prognosis between standard-risk group,high-risk adult group and high-risk children group were compared.Results There were no significant differences in all these T lymphocyte subsets among three groups at the three check points (P>0.05).Moreover,at the same time,comparable outcome had been achieved between standard-risk group (n=18),high-risk adult group (n=16) and high-risk children group (n=15).There were no differences in 2-y relapse incidence (27.8% vs 31.3% vs 26.7%,P=0.957),2-y non-relapse mortality (11.1% vs 0 vs 13.3%,P=0.185),2-y leukemia free survival (61.1% vs 68.8% vs 60.0%,P=0.834) and overall survival (77.8% vs 68.8% vs 60.0%,P=0.529) among the three groups.Incidence of grade Ⅱ-Ⅳ aGVHD was 44.4% vs 12.5% vs 46.7%(P=0.075) and incidence of cGVHD was 61.1% vs 50.0% vs 40.0% (P=0.249).Conclusion Comparison of immune reconstitution at early stage may be a reasonable cause to explain that equivalent outcomes were observed among high-and standard-risk Ph-negative ALL CR1 patients after HBMT.
4.Clinical analysis of letermovir for preventing cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation
Xianghan LIN ; Suping ZHANG ; Li LI ; Zhilei BIAN ; Siyu GAO ; Jinpeng FAN ; Yan LI ; Dingming WAN
Chinese Journal of Organ Transplantation 2024;45(11):796-802
Objective:To observe the efficacy and safety of letermovir in preventing cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Method:From September 2022 to September 2023, retrospective analysis was conducted for the relevant clinical data of 50 recipients of allo-HSCT at First Affiliated Hospital of Zhengzhou University Hospital. Letermovir prophylaxis was offered for preventing cytomegalovirus (CMV) reactivation post-transplantation. They were historically compared with previous patients at the same center without letermovir prophylaxis. The incidence of CMV reactivation, overall survival rate, engraftment status and other adverse events within 100 days post-transplant were compared between two groups. Propensity score matching (PSM) was utilized for controlling confounding factors. Univariate analyses were performed with t and chi-square tests while survival analysis conducted with Kaplan-Meier method.Result:In letermovir group, CMV reactivation was detected in 3 cases (6%) versus 23 cases (46%) in control group. Letermovir significantly reduced the incidence of post-transplant CMV reactivation ( P<0.01). Within Day 100 post-transplant, there was one death in letermovir group with an overall survival rate of 98%. In control group, three deaths occurred with an overall survival rate of 94%. The median survival time of deceased cases was 64 (58-81) day. No statistically significant inter-group difference existed in overall survival rate ( P=0.617). In letermovir group, secondary implantation failure was observed in 3 cases (6%) and it was lower than 12 cases (24%) in control group. Statistically significant inter-group difference existed in secondary implantation failure rate ( P=0.023). However, regarding timing of neutrophil engraftment ( P=0.054) and platelet engraftment ( P=0.649), there were no significant inter-group statistical differences. Hemorrhagic cystitis (HC) occurred in letermovir group (17 cses, 34%) and control group (27cases, 54%). The incidence of HC was significantly lower in letermovir group than that in control group ( P=0.044). However, no statistically significant inter-group difference existed in the incidence of post-transplant EBV infection or acute graft-versus-host disease. Conclusion:Letermovir may significantly lower the incidence of cytomegalovirus (CMV) reactivation after allo-HSCT. It is both effective and safe for preventing CMV disease and improving early outcomes.
5.Effect of CD34+ cell dose on haploidentical hematopoietic stem cell transplantation for treating malignant hematological diseases
Yingnan PENG ; Zhilei BIAN ; Suping ZHANG ; Li LI ; Weijie CAO ; Dingming WAN
Chinese Journal of Tissue Engineering Research 2024;28(1):1-6
BACKGROUND:Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose,but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE:To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center,Department of Hematology,First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included.Combining the results of previous studies and our center's experience,the cohort was divided into two groups using a CD34+ cell count of 5.0×106/kg as the cut-off point.Clinical outcomes related to graft implantation,relapse incidence,non-relapse mortality,overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION:(1)CD34+ cell dose correlated with platelet engraftment,with platelets implanted earlier in the high-dose group than in the low-dose group(14 days vs.16 days,P=0.013).(2)There was no significant difference in 3-year overall survival between the two groups(67.5%vs.53.8%,P=0.257);nor was there a significant difference in progression-free survival between the two groups(65.6%vs.44.2%,P=0.106),but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients(72.0%vs.49.3%,P=0.036).(3)The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group(16.0%vs.33.5%,P=0.05).(4)The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group,but there was no significant difference(17.3%vs.6.7%,P=0.070);stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group(20.0%vs.3.3%,P=0.046).(5)In conclusion,CD34+ cell doses>5.0×106/kg promote early platelet implantation,improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence.However,in high-risk patients,high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation,which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period.Therefore,it is considered that graft versus host disease monitoring should be enhanced in patients who transfused high-dose CD34+ cells.