Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
Managing Editor:Peng Lyu Mantle cell lymphoma(MCL),a relatively uncommon subtype of non-Hodgkin's lymphoma(NHL),constitutes approximately 2%-10%of NHL cases.Characterized by its inertness,aggressiveness,and incura...Managing Editor:Peng Lyu Mantle cell lymphoma(MCL),a relatively uncommon subtype of non-Hodgkin's lymphoma(NHL),constitutes approximately 2%-10%of NHL cases.Characterized by its inertness,aggressiveness,and incurability,MCL has a median overall survival(OS)of approximately 3-5 years.展开更多
Chimeric antigen receptor(CAR)T-cell therapy has achieved significant success in the treatment of hematological malignancies.In recent years,fast-growing CAR T clinical trials have actively explored their potential ap...Chimeric antigen receptor(CAR)T-cell therapy has achieved significant success in the treatment of hematological malignancies.In recent years,fast-growing CAR T clinical trials have actively explored their potential application scenarios.According to the data from the clinicaltrials.gov website,China became the country with the most registered CAR T trials in September 2017.As of June 30,2020,the number of registered CAR T trials in China has reached 357.In addition,as many as 150 other CAR T trials have been registered on ChiCTR.Although CAR T therapy is flourishing in China,there are still some problems that cannot be ignored.In this review,we aim to systematically summarize the clinical practice of CAR T-cell therapy in China.This review will provide an informative reference for colleagues in the field,and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.展开更多
Background:The impacts of previous cardio-cerebrovascular disease(pre-CCVD)on the outcomes of hematopoietic cell transplantation(HCT)are not well described.Patients with pre-CCVD may often be poor candidates for HCT.T...Background:The impacts of previous cardio-cerebrovascular disease(pre-CCVD)on the outcomes of hematopoietic cell transplantation(HCT)are not well described.Patients with pre-CCVD may often be poor candidates for HCT.This study aimed to investigate the impact of pre-CCVD on transplant outcomes.Methods:A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status.The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared.The primary endpoints were post-transplant cardio-cerebrovascular disease(post-CCVD)and non-relapse mortality(NRM).We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios(HRs).Results:The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group.No significant differences were noted in terms of engraftment,overall survival(OS)(67.00%vs.67.90%,P=0.983),or relapse(29.78%vs.28.26%,P=0.561)between the pre-CCVD group and the control group.The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls(14.68%vs.17.08%,P=0.670).However,pre-CCVD was associated with an increased incidence of post-CCVD(HR:12.50,95%confidence interval[CI]:3.88–40.30,P<0.001),which was an independent risk factor for increased NRM(HR:10.29,95%CI:3.84–27.62,P<0.001)and inferior OS(HR:10.29,95%CI:3.84–27.62,P<0.001).Conclusions:These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure,leading to a risk of post-CCVD.Post-CCVD was a powerful predictor for high NRM and inferior OS.Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.展开更多
To the Editor:Human pathogens have evolved over a long time to become mesophiles to adapt to the typical 37°C temperature of the human body.Yeast and yeast-like fungi also grow very well at this temperature,while...To the Editor:Human pathogens have evolved over a long time to become mesophiles to adapt to the typical 37°C temperature of the human body.Yeast and yeast-like fungi also grow very well at this temperature,while the optimal temperature for the growth of filamentous fungi is 25 to 28℃.Hainan Island in China has a tropical oceanic monsoon climate with indistinct seasons.The mean temperature at this place for many years has been 24.4℃,and the annual temperature variation is small;the precipitation is approximately 1718.6 mm,and the relative humidity is 82%.These unique weather characteristics provide a favorable growth environment for pathogens.Patients with hematologic malignancies have poor immunity and are susceptible to pathogens.This results in high nosocomial infection rates in patients with hematologic malignancies and frequent antibiotic use.Epidemiological surveys of different regions and hospitals can provide more guidance for clinical drug administration by hematologists in treating infections in patients with hematologic malignancies.展开更多
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金This work was supported by the National Natural Science Foundation of China(No.82200169).
文摘Managing Editor:Peng Lyu Mantle cell lymphoma(MCL),a relatively uncommon subtype of non-Hodgkin's lymphoma(NHL),constitutes approximately 2%-10%of NHL cases.Characterized by its inertness,aggressiveness,and incurability,MCL has a median overall survival(OS)of approximately 3-5 years.
基金supported by grants from the National Natural Science Foundation of China(Nos.81830002 and 31991171 to W.D.H.)the Leading Talents Grant of Science&Technology from Beijing(No.Z181100006318004 to W.D.H.).
文摘Chimeric antigen receptor(CAR)T-cell therapy has achieved significant success in the treatment of hematological malignancies.In recent years,fast-growing CAR T clinical trials have actively explored their potential application scenarios.According to the data from the clinicaltrials.gov website,China became the country with the most registered CAR T trials in September 2017.As of June 30,2020,the number of registered CAR T trials in China has reached 357.In addition,as many as 150 other CAR T trials have been registered on ChiCTR.Although CAR T therapy is flourishing in China,there are still some problems that cannot be ignored.In this review,we aim to systematically summarize the clinical practice of CAR T-cell therapy in China.This review will provide an informative reference for colleagues in the field,and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.
基金partially supported by grants from the Beijing Nova Program(No.2011114)the National Natural Science Foundation of China(Nos.82070178 and 81700122)+5 种基金the Beijing Natural Science Foundation of China(Nos.7172200 and 7132217)the Capital's Funds for Health Improvement and Research(No.2016-1-4082)the Fund Sponsorship of the Capital Public Health Project(No.Z171100000417037)Hainan Provincial Natural Science Foundation of China(No.818MS157)Military Translational Medicine Fund of Chinese PLA General Hospital(No.ZH19003)Medical big data and artificial intelligence development fund of Chinese PLA General Hospital(No.2019MBD-016).
文摘Background:The impacts of previous cardio-cerebrovascular disease(pre-CCVD)on the outcomes of hematopoietic cell transplantation(HCT)are not well described.Patients with pre-CCVD may often be poor candidates for HCT.This study aimed to investigate the impact of pre-CCVD on transplant outcomes.Methods:A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status.The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared.The primary endpoints were post-transplant cardio-cerebrovascular disease(post-CCVD)and non-relapse mortality(NRM).We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios(HRs).Results:The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group.No significant differences were noted in terms of engraftment,overall survival(OS)(67.00%vs.67.90%,P=0.983),or relapse(29.78%vs.28.26%,P=0.561)between the pre-CCVD group and the control group.The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls(14.68%vs.17.08%,P=0.670).However,pre-CCVD was associated with an increased incidence of post-CCVD(HR:12.50,95%confidence interval[CI]:3.88–40.30,P<0.001),which was an independent risk factor for increased NRM(HR:10.29,95%CI:3.84–27.62,P<0.001)and inferior OS(HR:10.29,95%CI:3.84–27.62,P<0.001).Conclusions:These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure,leading to a risk of post-CCVD.Post-CCVD was a powerful predictor for high NRM and inferior OS.Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.
基金This study was partially supported by a grant from the Hainan Provincial Natural Science Foundation of China(No.818MS157).
文摘To the Editor:Human pathogens have evolved over a long time to become mesophiles to adapt to the typical 37°C temperature of the human body.Yeast and yeast-like fungi also grow very well at this temperature,while the optimal temperature for the growth of filamentous fungi is 25 to 28℃.Hainan Island in China has a tropical oceanic monsoon climate with indistinct seasons.The mean temperature at this place for many years has been 24.4℃,and the annual temperature variation is small;the precipitation is approximately 1718.6 mm,and the relative humidity is 82%.These unique weather characteristics provide a favorable growth environment for pathogens.Patients with hematologic malignancies have poor immunity and are susceptible to pathogens.This results in high nosocomial infection rates in patients with hematologic malignancies and frequent antibiotic use.Epidemiological surveys of different regions and hospitals can provide more guidance for clinical drug administration by hematologists in treating infections in patients with hematologic malignancies.
