Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
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
Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells hav...Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells have not been fully explored.This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid(Lac)in the proliferation of myeloma cells and cell sensitivity to bortezomib(BTZ).Methods:Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients.The CCK8 assay and flow cytometry were used to detect cell proliferation,apoptosis,and cell cycle changes.Western blotting was used to detect the potential mechanism and apoptosis-and cycle-related protein changes.Results:Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients.It was significantly correlated with Durie-Salmon Staging(DS Staging)and the International Staging System(ISS Staging)and the serum and urinary involved/uninvolved free light chain ratios.Patients with relatively high lactate levels had a poor treatment response.Moreover,in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells,which was accompanied by an increased proportion of S-phase cells.In addition,Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2(NFκB2)and Re1B.Conclusion:Metabolic changes are important in MM cell proliferation and treatment response;lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.展开更多
Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an u...Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.展开更多
The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected ...The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.展开更多
Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPN...Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPNs,i.e.,polycythemia vera,essential thrombocythemia and primary myelofibrosis,exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites,e.g.,portal,splanchnic or hepatic veins,the placenta or cerebral sinuses.The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury,stasis,elevated leukocyte adhesion,integrins,neutrophil extracellular traps,somatic mutations(e.g.,the V617F point mutation in the JAK2 gene),microparticles,circulating endothelial cells,and other factors,to name a few.Herein,we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs,with a particular focus on its epidemiology,pathogenesis,histopathology,risk factors,classification,clinical presentation,diagnosis,and management.展开更多
Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell ac...Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.展开更多
BACKGROUND Obesity and diabetes are associated with high levels of oxidative stress.In Romanian patients with obesity and(or)diabetes,this association has not been sufficiently explored.AIM To evaluate oxidative stres...BACKGROUND Obesity and diabetes are associated with high levels of oxidative stress.In Romanian patients with obesity and(or)diabetes,this association has not been sufficiently explored.AIM To evaluate oxidative stress in obese and(or)diabetic subjects and to investigate the possible correlations between oxidative stress and anthropometric/biochemical parameters.METHODS Oxidative stress was evaluated from a single drop of capillary blood.Reactive oxygen species(ROS)were evaluated using the free oxygen radical test(FORT).The free oxygen radical defence(FORD)assay was used to measure antioxidant levels.RESULTS FORT levels were higher in obese subjects(3.04±0.36 mmol/L H2O2)vs controls(2.03±0.14 mmol/L H2O2)(P<0.0001).FORD levels were lower in obese subjects(1.27±0.13 mmol/L Trolox)vs controls(1.87±1.20 mmol/L Trolox)(P=0.0072).Obese diabetic subjects had higher FORT values(3.16±0.39 mmol/L H2O2)vs non-diabetic counterparts(2.99±0.33 mmol/L H2O2)(P=0.0233).In obese subjects,FORT values correlated positively with body mass index(BMI)(r=0.48,P=0.0000),waist circumference(WC)(r=0.31,P=0.0018),fasting plasma glucose(FPG)(r=0.31,P=0.0017),total cholesterol(TC)(r=0.27,P=0.0068)and uric acid(r=0.36,P=0.0001).FORD values correlated negatively with BMI(r=-0.43,P=0.00001),WC(r=-0.28,P=0.0049),FPG(r=-0.25,P=0.0130),TC(r=-0.23,P=0.0198)and uric acid(r=-0.35,P=0.0002).In obese diabetic subjects,FORT values correlated positively with BMI(r=0.49,P=0.0034)and TC(r=0.54,P=0.0217).FORD values were negatively associated with BMI(r=-0.54,P=0.0217)and TC(r=-0.58,P=0.0121).CONCLUSION Oxidative stress levels,as measured by the FORT and FORD assays,were higher in obese subjects vs controls.ROS levels were elevated in diabetic obese patients vs obese non-diabetic patients and controls.展开更多
Objective:To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia(AL)cells.Methods:The expression of Wnt pathway genes and cell cycle-related genes were analy...Objective:To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia(AL)cells.Methods:The expression of Wnt pathway genes and cell cycle-related genes were analyzed in two AL cell lines.Pyrophosphate sequencing was performed to determine the methylation degree.Then,the enrichment of H4K20mel and H3K9ac was determined using ChIP-qPCR.Flow cytometry was used to analyze the cell cycle.Results:The IC_(50) of genistein in the two AL cell lines was lower than that for the bone marrow mesenchymal stem cell line.Genistein upregulated H4K20mel,KMT5A and Wnt suppressor genes,including Wnt5a,and downregulated the downstream target genes of Wnt,such as c-myc and β-catenin.The methylation degree and H3K9ac enrichment in the Wnt5a promoter region remained unchanged.However,the enrichment of H4K20mel in the Wnt5a promoter and coding regions increased.In addition,genistein upregulated Phospho-cdc2,Mytl,Cyclin A,Cyclin E2,p21 and Phospho-histone H3,but downregulated Phospho-weel.Cell cycle arrest was induced in the G2/M phase.Conclusion:Genistein inhibits the activation of the Wnt pathway by promoting the expression of Wnt5a through the activation of KMT5A and enrichment of H4K20mel in the Wnt5a gene promoter and coding regions,rather than demethylation.Genistein also blocks the cell cycle in the G2/M phase.Therefore,genistein is a potential anti-leukemia drug.展开更多
AIM: To research the two homologous predicted proline-rich protein genes, Mus musculus predicted gene 4736(MP4) and proline-rich protein Bst NI subfamily1(Prb1) which were significantly upregulated in cultured corneal...AIM: To research the two homologous predicted proline-rich protein genes, Mus musculus predicted gene 4736(MP4) and proline-rich protein Bst NI subfamily1(Prb1) which were significantly upregulated in cultured corneal organs when encountering fungal pathogen preparations. This study was to confirm the expression and potential functions of these two genes in ocular surface.METHODS: A Pseudomonas aeruginosa keratitis model was established in Balb/c mice. One day post infection, m RNA level of MP4 was measured using real-time polymerase chain reaction(PCR), and MP4 protein detected by immunohistochemistry(IHC) or Western blot using a customized polyclonal anti-MP4 antibody preparation. Lacrimal glands from normal mice were also subjected to IHC staining for MP4. An online bioinformatics program, Bio GPS, was utilized to screen public data to determine other potential locations of MP4.RESULTS: One day after keratitis induction, MP4 was upregulated in the corneas at both m RNA level as measured using real-time PCR and protein levels as measured using Western blot and IHC. Bio GPS analysis of public data suggested that the MP4 gene was most abundantly expressed in the lacrimal glands, and IHC revealed that normal murine lacrimal glands were positive for MP4 staining.CONCLUSION: MP4 and Prb1 are closely related with the physiology and pathological processes of the ocular surface. Considering the significance of ocular surface abnormalities like dry eye, we propose that MP4 and Prb1 contribute to homeostasis of ocular surface, and deserve more extensive functional and disease correlation studies.展开更多
Objective:The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy,which is a strong predictor of mortality in patients with severe sepsis.Simvastatin plays an important role...Objective:The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy,which is a strong predictor of mortality in patients with severe sepsis.Simvastatin plays an important role in reducing inflammation.In addition,the gut has long been hypothesized to be the“motor”of critical illness,driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation.展开更多
Cancer immunotherapy,especially immune checkpoint blockade therapy(ICB),has revolutionized cancer treatment,providing a potential curable modality for advanced cancer patients.In immunogenic cancer,such as melanoma an...Cancer immunotherapy,especially immune checkpoint blockade therapy(ICB),has revolutionized cancer treatment,providing a potential curable modality for advanced cancer patients.In immunogenic cancer,such as melanoma and lung cancers with a history of smoking,approximately 30%patients with anti-programmed death 1(PD1)monotherapy survive more than 5 years.However,despite being a major breakthrough in the treatment of cancer,the majority of cancer patients have not yet benefited from ICB monotherapy^(1).Thus,innovative strategies to improve ICB efficacy are still needed.展开更多
Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host d...Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.展开更多
Background:Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia(AML)in first complete remission(CR1),the value of consolidatio...Background:Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia(AML)in first complete remission(CR1),the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial.Methods:We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation(MSDT)for patients with AML in CR1 in multicenters across China.In our study,we analyzed data of 373 AML patients in CR1 from three centers across China.Results:With a median follow-up of 969 days,patients with≥3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival(LFS)(85.6%vs.67.0%,P<0.001)and overall survival(89.2%vs.78.5%,P=0.007),and better cumulative incidences of relapse(10.5%vs.19.6%,P=0.020)and non-relapse mortality(4.2%vs.14.9%,P=0.001)than those with≤2 courses of consolidation chemotherapy.Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with≥3 courses of consolidation chemotherapy had a higher probability of LFS(85.9%vs.67.7%,P=0.003)and a lower cumulative incidence of relapse(9.6%vs.23.3%,P=0.013)than those with≤2 courses.Conclusion:Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.展开更多
Myeloproliferative neoplasms(MPNs)are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage.Affected individuals are at increased risk for cardiov...Myeloproliferative neoplasms(MPNs)are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage.Affected individuals are at increased risk for cardiovascular and thrombotic events.Myocardial infarction(MI)may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease.In the present review,we examine the epidemiology,pathogenesis,clinical presentation,and management of MI in MPNs based on the available literature.Moreover,we review potential biomarkers that could mediate the MI-MPNs crosstalk,from classical biochemical tests,e.g.,lactate dehydrogenase,creatine kinase and troponins,to pro-inflammatory cytokines,oxidative stress markers,and clonal hematopoiesis.展开更多
Sorafenib therapy improves overall survival(OS)in patients with FLT3 internal tandem duplication(ITD)acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation.We explored the efficacy of...Sorafenib therapy improves overall survival(OS)in patients with FLT3 internal tandem duplication(ITD)acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation.We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns.In this multi-center,cohort study,we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation.Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group,and otherwise to the control group.展开更多
Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after ...Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.展开更多
Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate ...Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017,a total of 128 patients who received auto-HSCT(n=72)or allo-HSCT(n=56)at eight medical centers across China were included in this study.We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease(95%vs.82%,P=0.027),bone marrow involvement(42%vs.15%,P=0.001),chemotherapy-resistant disease(41%vs.8%,P=0.001),and progression disease(32%vs.4%,P<0.001)at transplantation than those receiving auto-HSCT.With a median follow-up of 30(2–143)months,3-year overall survival(OS)and progression-free survival(PFS)in the auto-HSCT group were 70%(48/63)and 59%(42/63),respectively.Three-year OS and PFS for allo-HSCT recipients were 46%(27/54)and 44%(29/54),respectively.There was no difference in relapse rate(34%[17/63]in auto-HSCT vs.29%[15/54]in allo-HSCT,P=0.840).Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63)compared with 27%(14/54)for allo-HSCT recipients(P=0.004).Subanalyses showed that patients with lower prognostic index scores for PTCL(PIT)who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores(3-year OS:85%vs.40%,P=0.003).Patients with complete remission(CR)undergoing auto-HSCT had better survival(3-year OS:88%vs.48%in allo-HSCT,P=0.008).For patients beyond CR,the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group(3-year OS:51%vs.46%,P=0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China.Auto-HSCT seemed to be associated with better survival for patients in good condition(lower PIT score and/or better disease control).For patients possessing unfavorable characteristics,the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.展开更多
The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphom...The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
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the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
基金supported by grants from the National Natural Science Foundation of China(No.82070208)the Military Clinical Medical Innovation Project of Xinqiao Hospital(No.2021JSLC0003)+2 种基金the National Natural Science Foundation of Chongqing(No.cstc2020jcyjmsxmX0433)the Translational Research Grant of NCRCH(Nos.2020ZKZC02,2021WWB05)the Chongqing Science and Health Joint Medical Research Project(Nos.2021MSXM226,2023QNXM047).
文摘Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells have not been fully explored.This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid(Lac)in the proliferation of myeloma cells and cell sensitivity to bortezomib(BTZ).Methods:Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients.The CCK8 assay and flow cytometry were used to detect cell proliferation,apoptosis,and cell cycle changes.Western blotting was used to detect the potential mechanism and apoptosis-and cycle-related protein changes.Results:Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients.It was significantly correlated with Durie-Salmon Staging(DS Staging)and the International Staging System(ISS Staging)and the serum and urinary involved/uninvolved free light chain ratios.Patients with relatively high lactate levels had a poor treatment response.Moreover,in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells,which was accompanied by an increased proportion of S-phase cells.In addition,Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2(NFκB2)and Re1B.Conclusion:Metabolic changes are important in MM cell proliferation and treatment response;lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.
文摘Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.
文摘The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.
文摘Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPNs,i.e.,polycythemia vera,essential thrombocythemia and primary myelofibrosis,exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites,e.g.,portal,splanchnic or hepatic veins,the placenta or cerebral sinuses.The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury,stasis,elevated leukocyte adhesion,integrins,neutrophil extracellular traps,somatic mutations(e.g.,the V617F point mutation in the JAK2 gene),microparticles,circulating endothelial cells,and other factors,to name a few.Herein,we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs,with a particular focus on its epidemiology,pathogenesis,histopathology,risk factors,classification,clinical presentation,diagnosis,and management.
文摘Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.
文摘BACKGROUND Obesity and diabetes are associated with high levels of oxidative stress.In Romanian patients with obesity and(or)diabetes,this association has not been sufficiently explored.AIM To evaluate oxidative stress in obese and(or)diabetic subjects and to investigate the possible correlations between oxidative stress and anthropometric/biochemical parameters.METHODS Oxidative stress was evaluated from a single drop of capillary blood.Reactive oxygen species(ROS)were evaluated using the free oxygen radical test(FORT).The free oxygen radical defence(FORD)assay was used to measure antioxidant levels.RESULTS FORT levels were higher in obese subjects(3.04±0.36 mmol/L H2O2)vs controls(2.03±0.14 mmol/L H2O2)(P<0.0001).FORD levels were lower in obese subjects(1.27±0.13 mmol/L Trolox)vs controls(1.87±1.20 mmol/L Trolox)(P=0.0072).Obese diabetic subjects had higher FORT values(3.16±0.39 mmol/L H2O2)vs non-diabetic counterparts(2.99±0.33 mmol/L H2O2)(P=0.0233).In obese subjects,FORT values correlated positively with body mass index(BMI)(r=0.48,P=0.0000),waist circumference(WC)(r=0.31,P=0.0018),fasting plasma glucose(FPG)(r=0.31,P=0.0017),total cholesterol(TC)(r=0.27,P=0.0068)and uric acid(r=0.36,P=0.0001).FORD values correlated negatively with BMI(r=-0.43,P=0.00001),WC(r=-0.28,P=0.0049),FPG(r=-0.25,P=0.0130),TC(r=-0.23,P=0.0198)and uric acid(r=-0.35,P=0.0002).In obese diabetic subjects,FORT values correlated positively with BMI(r=0.49,P=0.0034)and TC(r=0.54,P=0.0217).FORD values were negatively associated with BMI(r=-0.54,P=0.0217)and TC(r=-0.58,P=0.0121).CONCLUSION Oxidative stress levels,as measured by the FORT and FORD assays,were higher in obese subjects vs controls.ROS levels were elevated in diabetic obese patients vs obese non-diabetic patients and controls.
基金supported by grants from the National Natural Science Foundation of China(No.81800167)the Natural Science Foundation of Fujian Province(No.2017J05132)+4 种基金the Fujian Provincial Health Technology Project(No.2018-ZQN-40)the Start-up Fund Project of Fujian Medical University(No.2016QH020)the Construction Project of Fujian Medical Center of Hematology(No.Min201704)the National and Fujian Provincial Key Clinical Specialty Discipline Construction Program,ChinaClinical Research Center for Hematological Malignancies of Fujian Province.
文摘Objective:To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia(AL)cells.Methods:The expression of Wnt pathway genes and cell cycle-related genes were analyzed in two AL cell lines.Pyrophosphate sequencing was performed to determine the methylation degree.Then,the enrichment of H4K20mel and H3K9ac was determined using ChIP-qPCR.Flow cytometry was used to analyze the cell cycle.Results:The IC_(50) of genistein in the two AL cell lines was lower than that for the bone marrow mesenchymal stem cell line.Genistein upregulated H4K20mel,KMT5A and Wnt suppressor genes,including Wnt5a,and downregulated the downstream target genes of Wnt,such as c-myc and β-catenin.The methylation degree and H3K9ac enrichment in the Wnt5a promoter region remained unchanged.However,the enrichment of H4K20mel in the Wnt5a promoter and coding regions increased.In addition,genistein upregulated Phospho-cdc2,Mytl,Cyclin A,Cyclin E2,p21 and Phospho-histone H3,but downregulated Phospho-weel.Cell cycle arrest was induced in the G2/M phase.Conclusion:Genistein inhibits the activation of the Wnt pathway by promoting the expression of Wnt5a through the activation of KMT5A and enrichment of H4K20mel in the Wnt5a gene promoter and coding regions,rather than demethylation.Genistein also blocks the cell cycle in the G2/M phase.Therefore,genistein is a potential anti-leukemia drug.
基金Supported by National Natural Science Foundation of China(No.81271050)
文摘AIM: To research the two homologous predicted proline-rich protein genes, Mus musculus predicted gene 4736(MP4) and proline-rich protein Bst NI subfamily1(Prb1) which were significantly upregulated in cultured corneal organs when encountering fungal pathogen preparations. This study was to confirm the expression and potential functions of these two genes in ocular surface.METHODS: A Pseudomonas aeruginosa keratitis model was established in Balb/c mice. One day post infection, m RNA level of MP4 was measured using real-time polymerase chain reaction(PCR), and MP4 protein detected by immunohistochemistry(IHC) or Western blot using a customized polyclonal anti-MP4 antibody preparation. Lacrimal glands from normal mice were also subjected to IHC staining for MP4. An online bioinformatics program, Bio GPS, was utilized to screen public data to determine other potential locations of MP4.RESULTS: One day after keratitis induction, MP4 was upregulated in the corneas at both m RNA level as measured using real-time PCR and protein levels as measured using Western blot and IHC. Bio GPS analysis of public data suggested that the MP4 gene was most abundantly expressed in the lacrimal glands, and IHC revealed that normal murine lacrimal glands were positive for MP4 staining.CONCLUSION: MP4 and Prb1 are closely related with the physiology and pathological processes of the ocular surface. Considering the significance of ocular surface abnormalities like dry eye, we propose that MP4 and Prb1 contribute to homeostasis of ocular surface, and deserve more extensive functional and disease correlation studies.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81873434)and the Natural Science Foundation of Hubei Province(No.2020CFA065).
文摘Objective:The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy,which is a strong predictor of mortality in patients with severe sepsis.Simvastatin plays an important role in reducing inflammation.In addition,the gut has long been hypothesized to be the“motor”of critical illness,driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81972877)the Collaborative Innovation Center of Hematologythe Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Cancer immunotherapy,especially immune checkpoint blockade therapy(ICB),has revolutionized cancer treatment,providing a potential curable modality for advanced cancer patients.In immunogenic cancer,such as melanoma and lung cancers with a history of smoking,approximately 30%patients with anti-programmed death 1(PD1)monotherapy survive more than 5 years.However,despite being a major breakthrough in the treatment of cancer,the majority of cancer patients have not yet benefited from ICB monotherapy^(1).Thus,innovative strategies to improve ICB efficacy are still needed.
基金supported by the National Key R&D Program of China(Grant No.2022YFA1103300)the National Natural Science Foundation of China(Grant No.82020108004)+3 种基金the Natural Science Foundation of Chongqing Innovation Group Science Program(Grant No.cstc2021jcyjcxttX0001)the Natural Science Foundation of Chongqing(Grant No.CSTB2022NSCQ-MSX1060)the Special Project for Talent Construction in Xinqiao Hospital(Grant No.2022XKRC001)the National College Student Innovation and Entrepreneurship Training Program(Grant No.202190035001).
文摘Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.
基金National Key Research and Development Program of China(No.2019YFC0840606)Ministry of Science and Technology,the National Natural Science Foundation of China(Nos.82070189,81621001 and 82270227)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2019-I2M-5-034)
文摘Background:Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia(AML)in first complete remission(CR1),the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial.Methods:We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation(MSDT)for patients with AML in CR1 in multicenters across China.In our study,we analyzed data of 373 AML patients in CR1 from three centers across China.Results:With a median follow-up of 969 days,patients with≥3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival(LFS)(85.6%vs.67.0%,P<0.001)and overall survival(89.2%vs.78.5%,P=0.007),and better cumulative incidences of relapse(10.5%vs.19.6%,P=0.020)and non-relapse mortality(4.2%vs.14.9%,P=0.001)than those with≤2 courses of consolidation chemotherapy.Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with≥3 courses of consolidation chemotherapy had a higher probability of LFS(85.9%vs.67.7%,P=0.003)and a lower cumulative incidence of relapse(9.6%vs.23.3%,P=0.013)than those with≤2 courses.Conclusion:Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.
文摘Myeloproliferative neoplasms(MPNs)are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage.Affected individuals are at increased risk for cardiovascular and thrombotic events.Myocardial infarction(MI)may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease.In the present review,we examine the epidemiology,pathogenesis,clinical presentation,and management of MI in MPNs based on the available literature.Moreover,we review potential biomarkers that could mediate the MI-MPNs crosstalk,from classical biochemical tests,e.g.,lactate dehydrogenase,creatine kinase and troponins,to pro-inflammatory cytokines,oxidative stress markers,and clonal hematopoiesis.
基金This work was supported by the National Natural Science Foundation of China(82170213 to L.X.,81970161 to Q.L.)the National Key Research and Development Projects of China(2021YFC2500301-4 to Q.L.,2022YFC2502600-5 to L.X.)Clinical Research Program of Nanfang Hospital,Southern Medical University(2021CR002 to L.X.).
文摘Sorafenib therapy improves overall survival(OS)in patients with FLT3 internal tandem duplication(ITD)acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation.We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns.In this multi-center,cohort study,we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation.Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group,and otherwise to the control group.
文摘Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.
文摘Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017,a total of 128 patients who received auto-HSCT(n=72)or allo-HSCT(n=56)at eight medical centers across China were included in this study.We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease(95%vs.82%,P=0.027),bone marrow involvement(42%vs.15%,P=0.001),chemotherapy-resistant disease(41%vs.8%,P=0.001),and progression disease(32%vs.4%,P<0.001)at transplantation than those receiving auto-HSCT.With a median follow-up of 30(2–143)months,3-year overall survival(OS)and progression-free survival(PFS)in the auto-HSCT group were 70%(48/63)and 59%(42/63),respectively.Three-year OS and PFS for allo-HSCT recipients were 46%(27/54)and 44%(29/54),respectively.There was no difference in relapse rate(34%[17/63]in auto-HSCT vs.29%[15/54]in allo-HSCT,P=0.840).Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63)compared with 27%(14/54)for allo-HSCT recipients(P=0.004).Subanalyses showed that patients with lower prognostic index scores for PTCL(PIT)who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores(3-year OS:85%vs.40%,P=0.003).Patients with complete remission(CR)undergoing auto-HSCT had better survival(3-year OS:88%vs.48%in allo-HSCT,P=0.008).For patients beyond CR,the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group(3-year OS:51%vs.46%,P=0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China.Auto-HSCT seemed to be associated with better survival for patients in good condition(lower PIT score and/or better disease control).For patients possessing unfavorable characteristics,the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
基金the National Natural Science Foundation of China(No.82070208)the Technique Innovation and Applied Program of Chongqing(No.cstc2019jscx-msxmX0187)+2 种基金the Natural Science Key Foundation of Chongqing(No.cstc2019jcyj-zdxmX0023)the Science and Technology Innovation Promotion Project of Army Medical University(No.2019XLC3020)the Translational Research Program of National Clinical Research Center for Hematologic Diseases(Nos.2020ZKZC02,2021WWB05).
文摘The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.
