Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of het...Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of heterogeneous diseases with different etiologies and treatment options. The three most common ABMFDs are aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Stem cell transplantation is the only treatment that can cure these diseases. However, due to high therapy-related mortality, stem cell transplantation has rarely been used as a first line treatment in treating ABMFD. With the advance of personalized medicine and precision medicine, various novel cellular therapy strategies are in trial to increase the efficiency and efficacy of ABMFD treatment. This article aims to review current available stem cell transplantation protocols and promising cellular therapy research in treating ABMFD.展开更多
Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce....Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce.We conducted a multicenter,population-based analysis of 932 consecutive patients.The three-year leukemia-free survival(LFS)rates were 56%for patients receiving both p/pDLI and intensified myeloablative conditioning(MAC)(intenseMAC)and 30%for those who received neither therapy per landmark analysis.Multivariable analyses were run separately for acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL),and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality.IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL,while there was no impact of intenseMAC observed in AML.p/pDLI achieved superior outcomes in both matched-sibling donor(MSD)and haploidentical donor transplantation,while intenseMAC only influenced MSD outcomes.Data suggest that RRAL patients receiving“total therapy”by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS,with p/pDLI being safer with a more extensive impact relative to intenseMAC.Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.展开更多
Chimeric antigen receptor(CAR)-T-cell therapy has achieved significant success in the treatment of hematologic malignancies.However,treatment-related toxicity and side effects remain the major drawbacks.As an importan...Chimeric antigen receptor(CAR)-T-cell therapy has achieved significant success in the treatment of hematologic malignancies.However,treatment-related toxicity and side effects remain the major drawbacks.As an important effector cell in innate immunity,natural killer(NK)cells exert strong antitumor functions and have better application prospects in the immunotherapy of hematologic malignancies.Compared with T cells,NK cells exhibit several advantages such as MHC-independent recognition.CAR-modified NK(CAR-NK)cells may exhibit a better ability of killing tumor cells.Herein,we review mainly preclinical data related to the development of CAR-NK cells in treating blood cancers.展开更多
基金Supported by AA and MDSIF research grant to Pu JJ,No.146818American Cancer Society grant to Pu JJ,No.124171-IRG-13-043-02a Pennsylvania State University College of Medicine research grant to Pu JJ
文摘Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of heterogeneous diseases with different etiologies and treatment options. The three most common ABMFDs are aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Stem cell transplantation is the only treatment that can cure these diseases. However, due to high therapy-related mortality, stem cell transplantation has rarely been used as a first line treatment in treating ABMFD. With the advance of personalized medicine and precision medicine, various novel cellular therapy strategies are in trial to increase the efficiency and efficacy of ABMFD treatment. This article aims to review current available stem cell transplantation protocols and promising cellular therapy research in treating ABMFD.
基金Supported by grants from the National Key Research and Development Program of China(2017YFA0104500)from the Ministry of Science and Technology,National Natural Science Foundation of China(81770189,81621001,and 81530046)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-034)+2 种基金Collaborative Innovation Center of Hematology China,the Science and Technology Project of Guangdong Province of China(2016B030230003)Peking University Clinical Scientist Program(BMU2019LCKXJ003)the Fundamental Research Funds for the Central Universities,and the Project of Health Collaborative Innovation of Guangzhou City(201704020214).We thank the principal investigators and the skilled teams at each of the participating sites.
文摘Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce.We conducted a multicenter,population-based analysis of 932 consecutive patients.The three-year leukemia-free survival(LFS)rates were 56%for patients receiving both p/pDLI and intensified myeloablative conditioning(MAC)(intenseMAC)and 30%for those who received neither therapy per landmark analysis.Multivariable analyses were run separately for acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL),and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality.IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL,while there was no impact of intenseMAC observed in AML.p/pDLI achieved superior outcomes in both matched-sibling donor(MSD)and haploidentical donor transplantation,while intenseMAC only influenced MSD outcomes.Data suggest that RRAL patients receiving“total therapy”by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS,with p/pDLI being safer with a more extensive impact relative to intenseMAC.Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.
文摘Chimeric antigen receptor(CAR)-T-cell therapy has achieved significant success in the treatment of hematologic malignancies.However,treatment-related toxicity and side effects remain the major drawbacks.As an important effector cell in innate immunity,natural killer(NK)cells exert strong antitumor functions and have better application prospects in the immunotherapy of hematologic malignancies.Compared with T cells,NK cells exhibit several advantages such as MHC-independent recognition.CAR-modified NK(CAR-NK)cells may exhibit a better ability of killing tumor cells.Herein,we review mainly preclinical data related to the development of CAR-NK cells in treating blood cancers.
