As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements...As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.展开更多
Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complic...Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.展开更多
Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic ...Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine(DAC) for treating patients with acute lymphoblastic leukemia(ALL) who relapsed after allogeneic hematopoietic stem cell transplantation(allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission(CR), 1 achieved a partial remission(PR), and 1 had no response(NR) after treatment at the latest follow-up(LFU), the median survival was 11.2 months(range, 3.8–34, 7 months). The 1-and 2-year overall survival(OS) rates were 50%(6/12) and 25%(3/12), respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL(57.1% vs. 20%). No aggravated flares of graft-versus-host disease(GVHD) were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.展开更多
Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentiall...Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.展开更多
BACKGROUND Allogeneic hematopoietic stem cell transplantation(allo-HSCT)may be related to the occurrence of complications,including graft-versus-host disease(GvHD)and infections.The pathogenesis of acute GvHD is conne...BACKGROUND Allogeneic hematopoietic stem cell transplantation(allo-HSCT)may be related to the occurrence of complications,including graft-versus-host disease(GvHD)and infections.The pathogenesis of acute GvHD is connected with T lymphocytes,which identify alloantigens on host's antigen-presenting cells,activate production of interferon-gamma(IFN-gamma)and interleukin-2(IL-2),and act on the immune effector cells and damage tissues and organs.AIM The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.METHODS We enrolled 62 patients,i.e.,30(48%)male and 32(52%)female subjects[median age 49.5(19-68)years],after allo-HSCT from siblings(n=12)or unrelated donors(n=50)due to acute myeloid leukemia with myeloablative conditioning(n=26;42%)and with non-myeloablative conditioning(n=36;58%).All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting.Blood samples were collected pre-transplant before and after(on day-1)the conditioning therapy and on days+2,+4,+6,+10,+20,and+30 after allo-HSCT.Serum levels of IL-2 and IFNgamma were determined using ELISA.RESULTS Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection.Group I included patients with neither acute GvHD nor infections[n=15(24%)],group II consisted of patients with infections without acute GvHD[n=17(27%)],group III was comprised of patients with acute GvHD without infections[n=9(15%)],and group IV included patients with both acute GvHD and infections[n=21(34%)].IFN-gamma concentrations were higher in Group II than in other groups on days+20(P=0.014)and+30(P=0.008).Post-hoc tests showed lower concentrations of IFN-gamma on day+30 in groups I(P=0.039)and IV(P=0.017)compared to group II.The levels of IL-2 were mostly undetectable.CONCLUSION Serum levels of IFN-gamma following allo-HSCT progressively escalate.High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD.Serum concentrations of IL-2 in most patients are undetectable.展开更多
Objective To investigate the effect of allgeneic hematopoietic stem cell transplantation ( allo - HSCT ) for β - thalassemia major. Methods Twenty - four β - thalassemia major patients with median age of 4 years ( r...Objective To investigate the effect of allgeneic hematopoietic stem cell transplantation ( allo - HSCT ) for β - thalassemia major. Methods Twenty - four β - thalassemia major patients with median age of 4 years ( range: 2 -15 years) ,18 boys and 6 girls,received al-展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.展开更多
BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen...BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen is not available.CASE SUMMARY A rare case of GS of the right breast and dorsal spine after complete remission of acute myelogenous leukemia is reported here.A 55-year-old female patient presented with a palpable,growing,painless lump as well as worsening dorsal compressive myelopathy.She had a history of acute myelomonocytic leukemia(AML M4)and achieved complete remission after chemotherapy following allogeneic hematopoietic stem cell transplantation.Imaging examinations showed the breast lump and C7-T1 epidural masses suspected of malignancy.Histologic results were compatible with GS in both the right breast and dorsal spine,which were considered extramedullary relapse of the AML treated 4 years earlier.CONCLUSION A rare case of GS relapse following allogeneic hematopoietic stem cell transplantation and guidelines for treatment are discussed.展开更多
Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Giv...Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Given the rapid development of genomics and immunotherapies,the interference strategies for AML recurrence have been changing these years.More and more novel targeting agents that have received the U.S.Food and Drug Administration(FDA)approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT relapse.Targeted strategies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually improved.Such agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT.This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.展开更多
Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neu...Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.展开更多
Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painfu...Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painful urination,which brings great pain.This study aimed to analyze risk factors of HC and its effect on patient survival.We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020.Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex,age,and diagnosis,and logistic regression analyses were used to identify factors associated with HC.We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups.We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)analysis.After propensity score matching,there were 131 patients each in the HC and non-HC groups.In the HC group,89 patients(67.9%)had mild HC(stage II°)and 43(32.1%)had severe HC(stage III–IV).The median interval between stem cell transplantation and HC development was 31(3–244)days.Univariate analysis indicated that donor age,hematopoietic stem cell source,HLA,acute graft-versus-host disease,busulfan,anti-thymocyte globulin(ATG),total body irradiation,cytomegalovirus(CMV)(urine),and BK polyomavirus(BKV)(urine)were significantly associated with HC.ATG,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate analysis.The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups(P=0.14).The 1-and 2-year survival rates in the HC group were 78.4%and 69.6%,respectively,and the corresponding rates in the non-HC group were 84.4%and 80.7%,respectively.ROC analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of HC.In conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for the development of HC.展开更多
This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT ...This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December 2017.Forty-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method(1:4).Primary graft failure including poor graft function and graft rejection did not occur in two groups.In BM hypoplasia and hyperplasia groups,the cumulative incidence(CI)of neutrophil engraftment at day 28(91.7%vs.93.8%,P=0.75),platelet engraftment at day 150(83.3%vs.93.8%,P=0.48),the median time to myeloid engraftment(14 days vs.14 days,P=0.85)and platelet engraftment(14 days vs.14 days,P=0.85)were comparable.The 3-year progression-free survival,overall survival,CI of non-relapse mortality and relapse were 67.8%vs.71.7%(P=0.98),69.8%vs.77.8%(P=0.69),18.5%vs.13.6%(P=0.66),and 10.2%vs.10.4%(P=0.82),respectively.In multivariate analysis,donor BM hypoplasia did not affect patient clinical outcomes after allo-HSCT.If patients have no other suitable donor,a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.展开更多
Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA chi...Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015.According to the source of donor,the展开更多
Objective To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma(PTCL).Methods From July 2007 to July 2014,60 cases of high risk PTCL were analyzed retrospectively...Objective To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma(PTCL).Methods From July 2007 to July 2014,60 cases of high risk PTCL were analyzed retrospectively.Results All 60 patients were at high risk group(carried with IPI≥3),with a median age of展开更多
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the standard of care for adult acute lymphoblastic leukemia (ALL) patients. In recent years, with the continuous development of immunotherapy...Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the standard of care for adult acute lymphoblastic leukemia (ALL) patients. In recent years, with the continuous development of immunotherapy, such as chimeric antigen receptor T cells, blinatumomab, and inotuzumab ozogamicin, a series of vital clinical studies have confirmed its high response rate and favorable outcomes for ALL. Although the emergence of immunotherapy has expanded relapsed or refractory (r/r) ALL patients’’ opportunities to receive allo-HSCT, allo-HSCT is associated with potential challenges. In this review, the role of allo-HSCT in the treatment of adult ALL in the era of immunotherapy will be discussed.展开更多
Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evalu...Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods: A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results: Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5%vs. 100%,P = 0.003;5-year event-free survival [EFS]: 54.1%vs. 83.4%,P = 0.010;5-year cumulative incidence of relapse [CIR]: 45.2%vs. 6.3%,P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1%vs. 54.1%,P = 0.041;5-year CIR: 11.6%vs. 45.2%,P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0%vs. 58.5%,P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR;age ≥10 years was an independent risk factor for OS and EFS;and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion: Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.展开更多
BACKGROUND Wells’ syndrome(eosinophilic cellulitis) is an uncommon eosinophilic dermatosis of uncertain pathogenesis,characterized by clinical polymorphism and suggestive but nonspecific histopathologic traits.Its co...BACKGROUND Wells’ syndrome(eosinophilic cellulitis) is an uncommon eosinophilic dermatosis of uncertain pathogenesis,characterized by clinical polymorphism and suggestive but nonspecific histopathologic traits.Its course is recurrent,and response to therapy is unpredictable.In a case in which the patient has a number of potential triggers for the manifestation of Wells’ syndrome skin rash,the treating physician must decide or must make an assumption in order to establish the most likely clinical scenario.This is important for the patient’s future treatment plans.CASE SUMMARY We describe the clinical case of a 46-year-old female with chronic lymphocytic leukemia who had already received treatment for several months with ibrutinib.She was diagnosed with Wells’ syndrome 10 d after an influenza vaccination containing thimerosal.Based on the literature,the patient was treated with a course of oral steroids.Resolution of clinical symptoms and rash were observed in response to the treatment.Ibrutinib was not discontinued.CONCLUSION The etiology of Wells’ syndrome remains unknown.Clinically,it resembles bacterial cellulitis.Lack of response to antibiotic treatment should lead the physician to consider a diagnosis of Wells’ syndrome.Treating the underlying condition is important and may lead to resolution of the syndrome.However,the most common and effective treatment to limit the course of the disease are systemic steroids.展开更多
Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that ...Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.展开更多
Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-r...Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-related quality of life(HR-QoL)after total therapy,which included allogeneic hematopoietic stem cell transplantation(allo-HSCT),and prophylactic donor lymphocyte infusion(DLI)in the early phase after transplantation,followed bymultiplemeasurable residual disease(MRD)and graft-versus-host disease(GvHD)-guided DLIs.Methods:Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study.If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse,severe infection,organ failure,and active GvHD at the time of planned DLI,prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen(HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT.Subsequently,multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.Results:A total of 105 patients were eligible.Eighty-seven patients received prophylactic DLI(group B),while 18 did not receive prophylactic DLI(group A).Among 105 patients,the cumulative incidence of grade 2-4 acute GvHD and chronic GvHDwas 40.6%(95%confidence interval[CI]=30.6%-50.6%)and 73.3%(95%CI=67.4%-79.2%),respectively.The cumulative incidence of relapse(CIR),transplant-related mortality(TRM),and leukemia-free survival(LFS)at 5 years after transplantation were 31.5%(95%CI=21.9%-41.1%),22.1%(95%CI=11.3%-32.9%),and 46.4%(95%CI=36.8%-56.0%),respectively.In group B,the CIR,TRM,and LFS at 5 years after transplantation were 27.6%(95%CI=17.6%-37.6%),21.6%(95%CI=11.2%-32.0%),and 50.8%(95%CI=40.0%-61.6%),respectively.At the end of follow-up,48 patients survived,and more than 90%of survivors had satisfactory recoveries of HR-QoL.Conclusions:Our study indicated that total therapy is not only associated with decreased CIR,comparable TRM,and better long-term LFS,but also with satisfactoryHR-QoL for refractory or relapsed AML,compared with those of standard of care therapy reported previously.Therefore,total therapymay be an optimized therapeutic strategy for refractory or relapsed AML.展开更多
Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hem...Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.Results:Of 359 patients,48.19%(173)patients experienced CMV infection within 100 days posttransplantation.In univariate and multivariate logistic analysis,haploidentical-related donor(HRD)(P<0.001;odds ratio[OR],5.542;95%confidence interval[CI],3.186–9.639),and ratio of CD3^(+)CD8^(+)cells in lymphocytes<14.825%(P<0.001;OR,3.005;95%CI,1.712–5.275)were identified as 2 independent risk factors.One-year relapse rate(RR)between the CMV infection group and the non-CMV infection group was not statistically significant(18.5%vs 19.9%,P=0.688).When we divided the total cohort into AML,ALL,and MAL subgroups,there were no significant differences as well(P=0.138;P=0.588;P=0.117;respectively).Conclusion:In conclusion,donor type(HRD)and the insufficient recovery of CD3^(+)CD8^(+)cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia.CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.展开更多
基金Supported by the Scientific Research Project of the Sichuan Province Education Department,No. 16ZA0241the National Natural Science Foundation of China,No. 82060268the Guangxi Natural Science Foundation of China,No. 2020JJA140124。
文摘As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
文摘Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.
基金supported by grants from the National Natural Science Foundation of China(No.81300412 and No.81470333)
文摘Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine(DAC) for treating patients with acute lymphoblastic leukemia(ALL) who relapsed after allogeneic hematopoietic stem cell transplantation(allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission(CR), 1 achieved a partial remission(PR), and 1 had no response(NR) after treatment at the latest follow-up(LFU), the median survival was 11.2 months(range, 3.8–34, 7 months). The 1-and 2-year overall survival(OS) rates were 50%(6/12) and 25%(3/12), respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL(57.1% vs. 20%). No aggravated flares of graft-versus-host disease(GVHD) were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
文摘Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.
文摘BACKGROUND Allogeneic hematopoietic stem cell transplantation(allo-HSCT)may be related to the occurrence of complications,including graft-versus-host disease(GvHD)and infections.The pathogenesis of acute GvHD is connected with T lymphocytes,which identify alloantigens on host's antigen-presenting cells,activate production of interferon-gamma(IFN-gamma)and interleukin-2(IL-2),and act on the immune effector cells and damage tissues and organs.AIM The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.METHODS We enrolled 62 patients,i.e.,30(48%)male and 32(52%)female subjects[median age 49.5(19-68)years],after allo-HSCT from siblings(n=12)or unrelated donors(n=50)due to acute myeloid leukemia with myeloablative conditioning(n=26;42%)and with non-myeloablative conditioning(n=36;58%).All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting.Blood samples were collected pre-transplant before and after(on day-1)the conditioning therapy and on days+2,+4,+6,+10,+20,and+30 after allo-HSCT.Serum levels of IL-2 and IFNgamma were determined using ELISA.RESULTS Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection.Group I included patients with neither acute GvHD nor infections[n=15(24%)],group II consisted of patients with infections without acute GvHD[n=17(27%)],group III was comprised of patients with acute GvHD without infections[n=9(15%)],and group IV included patients with both acute GvHD and infections[n=21(34%)].IFN-gamma concentrations were higher in Group II than in other groups on days+20(P=0.014)and+30(P=0.008).Post-hoc tests showed lower concentrations of IFN-gamma on day+30 in groups I(P=0.039)and IV(P=0.017)compared to group II.The levels of IL-2 were mostly undetectable.CONCLUSION Serum levels of IFN-gamma following allo-HSCT progressively escalate.High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD.Serum concentrations of IL-2 in most patients are undetectable.
文摘Objective To investigate the effect of allgeneic hematopoietic stem cell transplantation ( allo - HSCT ) for β - thalassemia major. Methods Twenty - four β - thalassemia major patients with median age of 4 years ( range: 2 -15 years) ,18 boys and 6 girls,received al-
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.
基金Supported by Youth Science Foundation of National Natural Science Foundation of China,No.81702598The Science Foundation of Guangdong Province,No.2017A030313803The Science and Technology Program of Guangzhou,No.201804010011
文摘BACKGROUND Granulocytic sarcoma(GS)is a rare malignant tumor,and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation.Currently,a standard treatment regimen is not available.CASE SUMMARY A rare case of GS of the right breast and dorsal spine after complete remission of acute myelogenous leukemia is reported here.A 55-year-old female patient presented with a palpable,growing,painless lump as well as worsening dorsal compressive myelopathy.She had a history of acute myelomonocytic leukemia(AML M4)and achieved complete remission after chemotherapy following allogeneic hematopoietic stem cell transplantation.Imaging examinations showed the breast lump and C7-T1 epidural masses suspected of malignancy.Histologic results were compatible with GS in both the right breast and dorsal spine,which were considered extramedullary relapse of the AML treated 4 years earlier.CONCLUSION A rare case of GS relapse following allogeneic hematopoietic stem cell transplantation and guidelines for treatment are discussed.
基金supported by the National Natural Science Foundation of China(Grant No.81302043)the Collaborative Innovation Center of Hematology,China
文摘Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Given the rapid development of genomics and immunotherapies,the interference strategies for AML recurrence have been changing these years.More and more novel targeting agents that have received the U.S.Food and Drug Administration(FDA)approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT relapse.Targeted strategies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually improved.Such agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT.This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.
基金supported by grants from Associazione Italiana per la Ricerca sul Cancro(AIRC,IG-20339)Ministero delllstruzione,deirUniversitci e della Ricerca(MIUR-PRIN 20177J4E75_004)Fondazione Cariverona to MAC。
文摘Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.
基金the National Natural Science Foundation of China(81670171 and 82070192)Key Project of Tianjin Natural Science Foundation(20JCZDJC00410)thrombocytopenia funding from the Yeehong Business School of Shenyang Pharmaceutical University(Sansheng TCP Young Research Funding,No.57).
文摘Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painful urination,which brings great pain.This study aimed to analyze risk factors of HC and its effect on patient survival.We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020.Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex,age,and diagnosis,and logistic regression analyses were used to identify factors associated with HC.We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups.We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)analysis.After propensity score matching,there were 131 patients each in the HC and non-HC groups.In the HC group,89 patients(67.9%)had mild HC(stage II°)and 43(32.1%)had severe HC(stage III–IV).The median interval between stem cell transplantation and HC development was 31(3–244)days.Univariate analysis indicated that donor age,hematopoietic stem cell source,HLA,acute graft-versus-host disease,busulfan,anti-thymocyte globulin(ATG),total body irradiation,cytomegalovirus(CMV)(urine),and BK polyomavirus(BKV)(urine)were significantly associated with HC.ATG,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate analysis.The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups(P=0.14).The 1-and 2-year survival rates in the HC group were 78.4%and 69.6%,respectively,and the corresponding rates in the non-HC group were 84.4%and 80.7%,respectively.ROC analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of HC.In conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for the development of HC.
基金supported by the National Natural Science Foundation of China(81670167)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)sponsored by the Fund for Fostering Young Scholars of Peking University Health Science Center(BMU2017PY010)
文摘This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December 2017.Forty-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method(1:4).Primary graft failure including poor graft function and graft rejection did not occur in two groups.In BM hypoplasia and hyperplasia groups,the cumulative incidence(CI)of neutrophil engraftment at day 28(91.7%vs.93.8%,P=0.75),platelet engraftment at day 150(83.3%vs.93.8%,P=0.48),the median time to myeloid engraftment(14 days vs.14 days,P=0.85)and platelet engraftment(14 days vs.14 days,P=0.85)were comparable.The 3-year progression-free survival,overall survival,CI of non-relapse mortality and relapse were 67.8%vs.71.7%(P=0.98),69.8%vs.77.8%(P=0.69),18.5%vs.13.6%(P=0.66),and 10.2%vs.10.4%(P=0.82),respectively.In multivariate analysis,donor BM hypoplasia did not affect patient clinical outcomes after allo-HSCT.If patients have no other suitable donor,a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.
文摘Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015.According to the source of donor,the
文摘Objective To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma(PTCL).Methods From July 2007 to July 2014,60 cases of high risk PTCL were analyzed retrospectively.Results All 60 patients were at high risk group(carried with IPI≥3),with a median age of
基金This work was supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001) , the Key Program of National Natural Science Foundation of China (No. 81530046) , the National Key Research and Development Program of China (No. 2017YFA0104500) , and the Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation (No. BMU2021PYB006) supported by the Fundamental Research Funds for the Central Universities.
文摘Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the standard of care for adult acute lymphoblastic leukemia (ALL) patients. In recent years, with the continuous development of immunotherapy, such as chimeric antigen receptor T cells, blinatumomab, and inotuzumab ozogamicin, a series of vital clinical studies have confirmed its high response rate and favorable outcomes for ALL. Although the emergence of immunotherapy has expanded relapsed or refractory (r/r) ALL patients’’ opportunities to receive allo-HSCT, allo-HSCT is associated with potential challenges. In this review, the role of allo-HSCT in the treatment of adult ALL in the era of immunotherapy will be discussed.
基金2018 Beijing Municipal Key Clinical Specialty Construction Project-Pediatrics(No. 2199000726)。
文摘Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods: A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results: Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5%vs. 100%,P = 0.003;5-year event-free survival [EFS]: 54.1%vs. 83.4%,P = 0.010;5-year cumulative incidence of relapse [CIR]: 45.2%vs. 6.3%,P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1%vs. 54.1%,P = 0.041;5-year CIR: 11.6%vs. 45.2%,P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0%vs. 58.5%,P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR;age ≥10 years was an independent risk factor for OS and EFS;and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion: Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.
文摘BACKGROUND Wells’ syndrome(eosinophilic cellulitis) is an uncommon eosinophilic dermatosis of uncertain pathogenesis,characterized by clinical polymorphism and suggestive but nonspecific histopathologic traits.Its course is recurrent,and response to therapy is unpredictable.In a case in which the patient has a number of potential triggers for the manifestation of Wells’ syndrome skin rash,the treating physician must decide or must make an assumption in order to establish the most likely clinical scenario.This is important for the patient’s future treatment plans.CASE SUMMARY We describe the clinical case of a 46-year-old female with chronic lymphocytic leukemia who had already received treatment for several months with ibrutinib.She was diagnosed with Wells’ syndrome 10 d after an influenza vaccination containing thimerosal.Based on the literature,the patient was treated with a course of oral steroids.Resolution of clinical symptoms and rash were observed in response to the treatment.Ibrutinib was not discontinued.CONCLUSION The etiology of Wells’ syndrome remains unknown.Clinically,it resembles bacterial cellulitis.Lack of response to antibiotic treatment should lead the physician to consider a diagnosis of Wells’ syndrome.Treating the underlying condition is important and may lead to resolution of the syndrome.However,the most common and effective treatment to limit the course of the disease are systemic steroids.
基金by grants from the National Basic Research Program of China(2015CB964402)the National Natural Science Foundation of China(81670171,81601369)+2 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-003 and 2018-I2M-HL-013)the Tianjin Science Funds for Distinguished Young Scholars(17JCJQJC45800)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2018PT32034 and 2019-RC-HL-013).
文摘Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.
基金Innovative Research Groups of the National Natural Science Foundation of China,Grant/Award Number:81621001National Key Research and Development Program of China,Grant/Award Number:2017YFA0104500National Natural Science Foundation of China,Grant/Award Number:81930004。
文摘Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-related quality of life(HR-QoL)after total therapy,which included allogeneic hematopoietic stem cell transplantation(allo-HSCT),and prophylactic donor lymphocyte infusion(DLI)in the early phase after transplantation,followed bymultiplemeasurable residual disease(MRD)and graft-versus-host disease(GvHD)-guided DLIs.Methods:Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study.If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse,severe infection,organ failure,and active GvHD at the time of planned DLI,prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen(HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT.Subsequently,multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.Results:A total of 105 patients were eligible.Eighty-seven patients received prophylactic DLI(group B),while 18 did not receive prophylactic DLI(group A).Among 105 patients,the cumulative incidence of grade 2-4 acute GvHD and chronic GvHDwas 40.6%(95%confidence interval[CI]=30.6%-50.6%)and 73.3%(95%CI=67.4%-79.2%),respectively.The cumulative incidence of relapse(CIR),transplant-related mortality(TRM),and leukemia-free survival(LFS)at 5 years after transplantation were 31.5%(95%CI=21.9%-41.1%),22.1%(95%CI=11.3%-32.9%),and 46.4%(95%CI=36.8%-56.0%),respectively.In group B,the CIR,TRM,and LFS at 5 years after transplantation were 27.6%(95%CI=17.6%-37.6%),21.6%(95%CI=11.2%-32.0%),and 50.8%(95%CI=40.0%-61.6%),respectively.At the end of follow-up,48 patients survived,and more than 90%of survivors had satisfactory recoveries of HR-QoL.Conclusions:Our study indicated that total therapy is not only associated with decreased CIR,comparable TRM,and better long-term LFS,but also with satisfactoryHR-QoL for refractory or relapsed AML,compared with those of standard of care therapy reported previously.Therefore,total therapymay be an optimized therapeutic strategy for refractory or relapsed AML.
基金This work was funded by grants from the CAMS Innovation Fund for Medical Sciences(CIFMS)(grant numbers 2021-1-I2M-017 and 2021-I2M-C&T-B-080).
文摘Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.Results:Of 359 patients,48.19%(173)patients experienced CMV infection within 100 days posttransplantation.In univariate and multivariate logistic analysis,haploidentical-related donor(HRD)(P<0.001;odds ratio[OR],5.542;95%confidence interval[CI],3.186–9.639),and ratio of CD3^(+)CD8^(+)cells in lymphocytes<14.825%(P<0.001;OR,3.005;95%CI,1.712–5.275)were identified as 2 independent risk factors.One-year relapse rate(RR)between the CMV infection group and the non-CMV infection group was not statistically significant(18.5%vs 19.9%,P=0.688).When we divided the total cohort into AML,ALL,and MAL subgroups,there were no significant differences as well(P=0.138;P=0.588;P=0.117;respectively).Conclusion:In conclusion,donor type(HRD)and the insufficient recovery of CD3^(+)CD8^(+)cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia.CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.
