Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy...Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy.However,the applicability of existing predictive models,CAR-HEMATOTOX(CAR-HT)for lymphoma,acute lymphoblastic leukemia-HEMATOTOX(ALL-HT)for B-ALL,and the early ICAHT prediction model(e IPM),remains uncertain across different hematologic malignancies.Methods:We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June2025,including B-ALL(n=62),T-ALL/non-Hodgkin's lymphoma(NHL)(n=25),and multiple myeloma(MM,n=32).The CAR-HT,ALL-HT,and e IPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.Results:Grade 3 ICAHT occurred in 32.3%of B-ALL,40.0%of T-ALL/NHL,and 25.0%of MM patients,while grade 4 rates were 33.9%,20.0%,and 6.3%,respectively.CAR-HT classified 67.2%of patients as high-risk,and ALL-HT identified 56.3%of ALL/NHL patients as high-risk.In both models,high-risk groups experienced significantly more prolonged neutropenia than low-risk groups(CAR-HT:17.7 vs.5.3 d,P<0.001;ALL-HT:21.3 vs.7.7 d,P<0.001).Both e IPMpre and e IPMpost strongly correlated with grade 3-4 ICAHT(P<0.001).Importantly,survival analysis showed that e IPMpre stratification distinguished outcomes:1-year overall survival(OS)was 65%in medium+high-risk vs.84%in low-risk patients(P=0.006),and 1-year disease-free survival(DFS)was 44%vs.73%(P<0.001).Similar predictive accuracy was observed with e IPMpost.Conclusions:The CAR-HT,ALL-HT,and e IPM models consistently identify patients at high risk for severe ICAHT across B-ALL,T-ALL/NHL,and MM.Among these,the e IPM stands out as a promising universal tool for survival prediction.These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.展开更多
基金supported by National Key Research and Development Plan of China(No.2022YFC2502606,2021YFA1100902)Beijing Nova Program of Science and Technology(No.20230484446)+2 种基金Peking University People’s Hospital(No.RZ2024-01)Joint Research Project of the Shijiazhuang-Peking University Cooperation Program,Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501200)National Natural Science Foundation of China(No.82350105,82270228)。
文摘Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy.However,the applicability of existing predictive models,CAR-HEMATOTOX(CAR-HT)for lymphoma,acute lymphoblastic leukemia-HEMATOTOX(ALL-HT)for B-ALL,and the early ICAHT prediction model(e IPM),remains uncertain across different hematologic malignancies.Methods:We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June2025,including B-ALL(n=62),T-ALL/non-Hodgkin's lymphoma(NHL)(n=25),and multiple myeloma(MM,n=32).The CAR-HT,ALL-HT,and e IPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.Results:Grade 3 ICAHT occurred in 32.3%of B-ALL,40.0%of T-ALL/NHL,and 25.0%of MM patients,while grade 4 rates were 33.9%,20.0%,and 6.3%,respectively.CAR-HT classified 67.2%of patients as high-risk,and ALL-HT identified 56.3%of ALL/NHL patients as high-risk.In both models,high-risk groups experienced significantly more prolonged neutropenia than low-risk groups(CAR-HT:17.7 vs.5.3 d,P<0.001;ALL-HT:21.3 vs.7.7 d,P<0.001).Both e IPMpre and e IPMpost strongly correlated with grade 3-4 ICAHT(P<0.001).Importantly,survival analysis showed that e IPMpre stratification distinguished outcomes:1-year overall survival(OS)was 65%in medium+high-risk vs.84%in low-risk patients(P=0.006),and 1-year disease-free survival(DFS)was 44%vs.73%(P<0.001).Similar predictive accuracy was observed with e IPMpost.Conclusions:The CAR-HT,ALL-HT,and e IPM models consistently identify patients at high risk for severe ICAHT across B-ALL,T-ALL/NHL,and MM.Among these,the e IPM stands out as a promising universal tool for survival prediction.These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.
