Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,ven...Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.展开更多
Measurable residual disease(MRD)has become a critical biomarker in the management of acute lymphoblastic leukemia(ALL),particularly for patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)...Measurable residual disease(MRD)has become a critical biomarker in the management of acute lymphoblastic leukemia(ALL),particularly for patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).The incorporation of MRD-directed strategies into clinical practice can enable personalized therapy and improve outcomes in ALL patients.Growing evidence has demonstrated that MRD status not only reflects the treatment response and relapse risk but also informs clinical decisions across the transplant continuum,including transplant indications,donor selection,conditioning regimens,and post-transplant interventions.With the advent of highly sensitive technologies such as real-time polymerase chain reaction and next-generation sequencing,MRD assessment has reached unprecedented accuracy,enabling precision medicine for ALL.This review systematically addresses six key clinical questions related to the application of MRD in ALL patients undergoing transplantation.We discuss optimal MRD detection methods,timing and sampling strategies,the prognostic implications of MRD positivity or clearance,and MRD-directed approaches before and after allo-HSCT.We further highlight emerging immunotherapeutic options and research gaps that must be addressed to refine MRD-guided strategies.In summary,incorporating MRD evaluation into routine clinical practice has the potential to optimize transplant outcomes and reduce relapse in ALL patients.展开更多
Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associat...Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associated with inferior transplant outcomes.In this prospective study,we aimed to investigate the prognostic value of post-HSCT MRD in relapse prediction in MDS.Methods:A total of 166 patients diagnosed with MDS were prospectively enrolled in this study.The KaplanMeier method was used to calculate the survival probabilities.Potential risk factors for outcomes after transplantation were evaluated through univariate and multivariate Cox regression models.Results:For patients with negative and positive post-HSCT MRD,the cumulative incidence of relapse(CIR)and disease-free survival(DFS)at 3 years were 5.9%and 69.6%(P<0.001)and 82.7%and 26.1%(P<0.001),respectively.In the multivariate analysis,post-HSCT MRD(HR=22.801,P<0.001)and Revised International Prognostic Scoring System(IPSS-R)risk stratification(HR=4.346,P=0.003)were independently correlated with relapse.A scoring system for relapse prediction was built based on post-HSCT MRD and IPSS-R stratification.The cumulative incidence of relapse at 3 years was 1.1%,15.8%,and 91.7%for patients with scores of 0,1,and 2,respectively(P<0.001).Conclusions:Our results demonstrated both post-HSCT MRD and IPSS-R scores were independent prognostic factors for OS,DFS,and relapse for MDS patients after allo-HSCT.The risk score system could better predict transplant outcomes and refine the risk stratification than alone in patients with MDS.展开更多
Measurable residual disease(MRD)has been widely recognized as a biomarker for deeply evaluating complete remission(CR),predicting relapse,guiding pre-emptive interventions,and serving as an endpoint surrogate for drug...Measurable residual disease(MRD)has been widely recognized as a biomarker for deeply evaluating complete remission(CR),predicting relapse,guiding pre-emptive interventions,and serving as an endpoint surrogate for drug testing.However,despite the emergence of new technologies,there remains a lack of comprehensive understanding regarding the proper techniques,sample materials,and optimal time points for MRD assessment.In this review,we summarized the MRD methods,sample sources,and evaluation frequency according to the risk category of the European Leukemia Net(ELN)2022.Additionally,we emphasize the importance of properly utilizing and combining these technologies.We have also refined the flowchart outlining each time point for preemptive interventions and intervention paths.The evaluation of MRD in acute myeloid leukemia(AML)is sophisticated,clinically applicable,and technology-dependent,and necessitates standardized approaches and further research.展开更多
Donor selection determines the occurrence of acute graft-versus-host-disease(aGVHD)following allogeneic hematopoietic stem cell transplantation(allo-HSCT).To optimize the current clinical donor selection criteria and ...Donor selection determines the occurrence of acute graft-versus-host-disease(aGVHD)following allogeneic hematopoietic stem cell transplantation(allo-HSCT).To optimize the current clinical donor selection criteria and identify putative donor lymphocyte subsets associated with better recipient outcomes,we analyzed the peripheral CD4^(+)and CD8^(+)subsets in 80 granulocyte colonystimulating factor(G-CSF)mobilized donors and examined the aGVHD incidence of the corresponding 80 haploidentical and identical allo-HSCT recipients.The G-CSF-induced expansion of subsets varied among donors.We discovered a novel PD-1^(+)CD8^(+)CD45RA^(+)CCR7^(+)T lymphocyte subset in suitable donors that was significantly correlated with lower incidence of aGVHD and post-transplant anti-infection.The anti-aGVHD activity of this subset was confirmed in a validation cohort(n=30).Single-cell RNA sequencing revealed that this T cell subset exhibited transcriptomic features of stem cell-like memory T cell(TSCM)with both Treg and Teff activities which indicated its dual functions in aGVHD inhibition and graft-versus-leukemia(GVL)effect.Intriguingly,upon G-CSF mobilization,the donor PD-1^(+)CD8^(+)TSCM-like regulatory cells increased the PD-1 expression in a BCL6-dependent manner.Next,we showed that the mouse counterpart of this subset(PD-1^(+)CD8^(+)CD44^(-)CD62L^(+))ameliorated aGVHD,and confirmed the existence of this subset in clinical recipients.In summary,we,for the first time,identified a novel donor peripheral T cell subset suppressing aGVHD while promoting the immune reconstitution of recipients.It may serve as an indicator for optimal haploidentical and identical donor selection.Importantly,the dual Treg and Teff function of these T cells makes it a promising treatment for not only aGVHD but also auto-immune diseases.展开更多
Background:The level of measurable residual disease(MRD)before and after transplantation is related to inferior transplant outcomes,and post-hematopoietic stem cell transplantation measurable residual disease(post-HSC...Background:The level of measurable residual disease(MRD)before and after transplantation is related to inferior transplant outcomes,and post-hematopoietic stem cell transplantation measurable residual disease(post-HSCT MRD)has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease(pre-HSCT MRD).However,only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia(ALL).This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:A total of 1683 ALL patients from Peking University People’s Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD.Cox proportional hazard regression models were built for time-to-event outcomes.Multivariable analysis was performed to determine independent influencing factors from the univariable analysis.Results:Both in total patients and in T-cell ALL or B-cell ALL,pediatric or adult,human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups,positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity(P<0.001 for all).Disease status(complete remission 1[CR1]vs.≥CR2)was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL,pediatric,or haploidentical SCT subgroups(P=0.027;P=0.003;P=0.035;P=0.003,respectively).A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status.The cumulative incidence of post-HSCT MRD positivity was 12.3%,25.1%,and 38.8%for subjects with scores of 0,1,and 2–3,respectively(P<0.001).Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival.Conclusion:Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.展开更多
Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxici...Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice.This review will focus on how the new era in which "everyone has a donor" will become a reality in China.展开更多
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2...The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD） （HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.展开更多
The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation(HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival af...The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation(HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival after HBMT versus haploidentical rhG-CSF-mobilized peripheral blood stem cell transplantation(HPBSCT) for acute leukemia(AL) not in remission(NR) or in more than the second complete remission(>CR2). To test the hypothesis that HBMT is still superior to HPBSCT for patients with AL, multiple myeloma(MM), or non-Hodgkin lymphoma(NHL) in CR1/CR2 and for patients with chronic myeloid leukemia in the first and second chronic phase lacking a matched donor, we designed a propensity score method-based multicenter study.Hematopoietic recovery, acute graft-versus-host disease(aGVHD), and chronic GVHD were comparable between the HBMT group(n=168) and the HPBSCT group(n=42). No significant differences were found in non-relapse mortality rate(20.17%±3.58%and 27.24%±7.16%, P=0.18) or relapse rate(19.96%±3.72% and 28.49%±8.25%, P=0.32) between the HBMT group and the HPBSCT group. HBMT recipients had better overall survival(65.0%±4.2% and 54.2%±8.3%, P=0.037) and disease-free survival(59.9%±4.6% and 44.3%±8.7%, P=0.051). Multivariate analysis showed that HPBSCT was associated with poorer DFS(HR(95%CI), 1.639(0.995–2.699), P=0.052). Our comparisons showed that HBMT was superior to HPBSCT as a post-remission treatment for patients lacking an identical donor.展开更多
Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the n...Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period.Regulatory T cells(Tregs)are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses.The features of Tregs in the neonatal liver under steady-state conditions are not well understood.The present study aimed to investigate the phenotype,functions,and significance of neonatal Tregs in the liver.We found a wave of thymus-derived Treg influx into the liver during 1–2 weeks of age.Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder.More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation,and the liver Tregs acquired stronger suppressive functions.The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARγand T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses.The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.展开更多
Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,swit...Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA.We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia(ITP)patients.Methods:This prospective,open-label,observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China.The study evaluated response rates and platelet counts at different time points after the switch,bleeding events,time to response,duration of response,and adverse events.Results:At 6 weeks after switching,response was observed in 21/49 patients(43%)who switched for inefficacy and 34/47 patients(72%)who switched for non-efficacy-related issues.In the inefficacy group,9/27 patients(33%)responded to eltrombopag,and 12/22 patients(55%)responded to rh-TPO.In the non-efficacy-related group,21/26(81%)and 13/21(62%)patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching,respectively.Response at 6 months was achieved in 24/49 patients(49%)switching for inefficacy and 37/47 patients(79%)switching for non-efficacy issues.In the inefficacy group,13/27 patients(48%)responded to eltrombopag,and 11/22 patients(50%)responded to rh-TPO.In the non-efficacy-related group,22/26 patients(85%)and 15/21 patients(71%)in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching,respectively.Both eltrombopag and rh-TPO were well tolerated.Conclusions:Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA.When the switch was motivated by other reasons,including patient preference and platelet count fluctuations,the probability of response was high.Registration:ClinicalTrials.gov,NCT04214951.展开更多
Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MR...Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRDnegative group(MRD‒_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD‒_CD8 clusters and vice versa.MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD‒_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.展开更多
Acute graft-versus-host disease(a GVHD)is caused by allo-activated donor T cells infiltrating target organs.As a regulator of immune function,granulocyte colony-stimulating factor(G-CSF)has been demonstrated to reliev...Acute graft-versus-host disease(a GVHD)is caused by allo-activated donor T cells infiltrating target organs.As a regulator of immune function,granulocyte colony-stimulating factor(G-CSF)has been demonstrated to relieve the a GVHD reaction.However,the role of G-CSF-primed donor Tcells in specific target organs is still unknown.In this study,we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c)and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group.This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model,especially in the lung and gut.Moreover,we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs.In addition,G-CSF treatment inhibited inducible co-stimulator(ICOS)expression and increased the expression of tolerance-related genes in recipient mice.Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD,especially for its precise regulation in GVHD target organs.展开更多
Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relati...Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9%vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001).The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%,respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions(P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.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
To the Editor:For recipients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),allogeneic hematopoietic stem cell transplantation(allo-HSCT)often fails to provide them with a satisfactory prognos...To the Editor:For recipients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),allogeneic hematopoietic stem cell transplantation(allo-HSCT)often fails to provide them with a satisfactory prognosis.The chimeric antigen receptor T(CAR-T)cells are proven to be safe and effective for these patients.[1]But there are few published studies assessing the advantages of CAR-T compared to traditional chemotherapy as a bridging treatment followed by HSCT.Consequently,we conducted this study to confirm whether children and young adult R/R B-ALL patients with CAR-T therapy could expect a better post-HSCT prognosis,compared to R/R patients only receiving traditional chemotherapy before transplantation.展开更多
Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role ...Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.展开更多
To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution （IR） in 144 patients who received allogeneic stem ceil transplantation （a...To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution （IR） in 144 patients who received allogeneic stem ceil transplantation （alio- SCT） and without showing any of the following events： poor graft function, grades II-IV acute graft-versus-host disease （GVHD）, serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3~ T cells, CD8~ T cells, and CD19~ B cells, and very slow in CD4~ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune ceils need not reach those in healthy donor in the first year after transplantation. We suggest that data from this recipient cohort should be used as reference values for post-transplant immune ceil counts in patients receiving HSCT.展开更多
Skin and soft tissue infections(SSTIs)refer to infections involving the skin,subcutaneous tissue,fascia,and muscle.In transplant populations with hematological malignancies,an immunocompromised status and the routine ...Skin and soft tissue infections(SSTIs)refer to infections involving the skin,subcutaneous tissue,fascia,and muscle.In transplant populations with hematological malignancies,an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly.However,to date,the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation(HSCT)patients remain unclear.This study included 228 patients(3.67%)who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital.The overall annual survival rate was 71.5%.We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure(PPGF),comorbidities of acute kidney injury(AKI),and hospital-acquired pneumonia(HAP)were independent risk factors for death in the study population.A PPGF-AKI-HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP.The areas under the curves of internal and external validation were 0.833(95%CI 0.760–0.906)and 0.826(95%CI 0.715–0.937),respectively.The calibration plot revealed the high consistency of the estimated risks,and decision curve analysis showed considerable net benefits for patients.展开更多
基金supported by the Beijing Natural Science Foundation(No.Z230016)the National Key Research and Development Program of China(No.2022YFC 2502606)+4 种基金the Major Program of the National Natural Science Foundation of China(No.82293630)the Peking University Medicine Fund for the World’s Leading Discipline or Discipline Cluster Development(No.71003Y3035)the Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)the National Natural Science Foundation of China(No.82170208)the Fundamental Research Funds for the Central Universities。
文摘Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.
基金partly supported by grants from the Beijing Municipal Science and Technology Commission(No.Z221100007422008)the National Natural Science Foundation of China(No.82293630 and 82293633)。
文摘Measurable residual disease(MRD)has become a critical biomarker in the management of acute lymphoblastic leukemia(ALL),particularly for patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).The incorporation of MRD-directed strategies into clinical practice can enable personalized therapy and improve outcomes in ALL patients.Growing evidence has demonstrated that MRD status not only reflects the treatment response and relapse risk but also informs clinical decisions across the transplant continuum,including transplant indications,donor selection,conditioning regimens,and post-transplant interventions.With the advent of highly sensitive technologies such as real-time polymerase chain reaction and next-generation sequencing,MRD assessment has reached unprecedented accuracy,enabling precision medicine for ALL.This review systematically addresses six key clinical questions related to the application of MRD in ALL patients undergoing transplantation.We discuss optimal MRD detection methods,timing and sampling strategies,the prognostic implications of MRD positivity or clearance,and MRD-directed approaches before and after allo-HSCT.We further highlight emerging immunotherapeutic options and research gaps that must be addressed to refine MRD-guided strategies.In summary,incorporating MRD evaluation into routine clinical practice has the potential to optimize transplant outcomes and reduce relapse in ALL patients.
基金partly supported by grants from the Beijing Municipal Science and Technology Commission(No.Z221100007422008)。
文摘Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associated with inferior transplant outcomes.In this prospective study,we aimed to investigate the prognostic value of post-HSCT MRD in relapse prediction in MDS.Methods:A total of 166 patients diagnosed with MDS were prospectively enrolled in this study.The KaplanMeier method was used to calculate the survival probabilities.Potential risk factors for outcomes after transplantation were evaluated through univariate and multivariate Cox regression models.Results:For patients with negative and positive post-HSCT MRD,the cumulative incidence of relapse(CIR)and disease-free survival(DFS)at 3 years were 5.9%and 69.6%(P<0.001)and 82.7%and 26.1%(P<0.001),respectively.In the multivariate analysis,post-HSCT MRD(HR=22.801,P<0.001)and Revised International Prognostic Scoring System(IPSS-R)risk stratification(HR=4.346,P=0.003)were independently correlated with relapse.A scoring system for relapse prediction was built based on post-HSCT MRD and IPSS-R stratification.The cumulative incidence of relapse at 3 years was 1.1%,15.8%,and 91.7%for patients with scores of 0,1,and 2,respectively(P<0.001).Conclusions:Our results demonstrated both post-HSCT MRD and IPSS-R scores were independent prognostic factors for OS,DFS,and relapse for MDS patients after allo-HSCT.The risk score system could better predict transplant outcomes and refine the risk stratification than alone in patients with MDS.
基金supported by Beijing Nova Program of Science and Technology (No.Z211100002121058)National Natural Science Foundation of China (No.82100168)+2 种基金Peking University People’s Hospital Research and Development Funds (No.RS2020-03,RDY2020-29)Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation“the Fundamental Research Funds for the Central Universities”(No.BMU2021PYB005)
文摘Measurable residual disease(MRD)has been widely recognized as a biomarker for deeply evaluating complete remission(CR),predicting relapse,guiding pre-emptive interventions,and serving as an endpoint surrogate for drug testing.However,despite the emergence of new technologies,there remains a lack of comprehensive understanding regarding the proper techniques,sample materials,and optimal time points for MRD assessment.In this review,we summarized the MRD methods,sample sources,and evaluation frequency according to the risk category of the European Leukemia Net(ELN)2022.Additionally,we emphasize the importance of properly utilizing and combining these technologies.We have also refined the flowchart outlining each time point for preemptive interventions and intervention paths.The evaluation of MRD in acute myeloid leukemia(AML)is sophisticated,clinically applicable,and technology-dependent,and necessitates standardized approaches and further research.
基金supported by grants from the National Key Research and Development Program of China(2017YFA0104500)the Program for Scientific and Technological Innovation from the Science and Technology Commission of Shanghai Municipality(22490760400)+1 种基金the National Natural Science Foundation of China(Grant No.82071856,81671579,81930004)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302).
文摘Donor selection determines the occurrence of acute graft-versus-host-disease(aGVHD)following allogeneic hematopoietic stem cell transplantation(allo-HSCT).To optimize the current clinical donor selection criteria and identify putative donor lymphocyte subsets associated with better recipient outcomes,we analyzed the peripheral CD4^(+)and CD8^(+)subsets in 80 granulocyte colonystimulating factor(G-CSF)mobilized donors and examined the aGVHD incidence of the corresponding 80 haploidentical and identical allo-HSCT recipients.The G-CSF-induced expansion of subsets varied among donors.We discovered a novel PD-1^(+)CD8^(+)CD45RA^(+)CCR7^(+)T lymphocyte subset in suitable donors that was significantly correlated with lower incidence of aGVHD and post-transplant anti-infection.The anti-aGVHD activity of this subset was confirmed in a validation cohort(n=30).Single-cell RNA sequencing revealed that this T cell subset exhibited transcriptomic features of stem cell-like memory T cell(TSCM)with both Treg and Teff activities which indicated its dual functions in aGVHD inhibition and graft-versus-leukemia(GVL)effect.Intriguingly,upon G-CSF mobilization,the donor PD-1^(+)CD8^(+)TSCM-like regulatory cells increased the PD-1 expression in a BCL6-dependent manner.Next,we showed that the mouse counterpart of this subset(PD-1^(+)CD8^(+)CD44^(-)CD62L^(+))ameliorated aGVHD,and confirmed the existence of this subset in clinical recipients.In summary,we,for the first time,identified a novel donor peripheral T cell subset suppressing aGVHD while promoting the immune reconstitution of recipients.It may serve as an indicator for optimal haploidentical and identical donor selection.Importantly,the dual Treg and Teff function of these T cells makes it a promising treatment for not only aGVHD but also auto-immune diseases.
基金partly supported by grants from the Beijing Municipal Science and Technology Commission(No.Z221100007422008)the National Natural Science Foundation of China(No.81930004).
文摘Background:The level of measurable residual disease(MRD)before and after transplantation is related to inferior transplant outcomes,and post-hematopoietic stem cell transplantation measurable residual disease(post-HSCT MRD)has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease(pre-HSCT MRD).However,only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia(ALL).This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:A total of 1683 ALL patients from Peking University People’s Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD.Cox proportional hazard regression models were built for time-to-event outcomes.Multivariable analysis was performed to determine independent influencing factors from the univariable analysis.Results:Both in total patients and in T-cell ALL or B-cell ALL,pediatric or adult,human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups,positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity(P<0.001 for all).Disease status(complete remission 1[CR1]vs.≥CR2)was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL,pediatric,or haploidentical SCT subgroups(P=0.027;P=0.003;P=0.035;P=0.003,respectively).A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status.The cumulative incidence of post-HSCT MRD positivity was 12.3%,25.1%,and 38.8%for subjects with scores of 0,1,and 2–3,respectively(P<0.001).Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival.Conclusion:Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
基金the National Natural Science Foundation of China (Nos.81873445, 81470342, and 81670168)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No.81621001)the Key Program of the National Natural Science Foundation of China (Nos.81530046 and 81230013).
文摘Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice.This review will focus on how the new era in which "everyone has a donor" will become a reality in China.
基金supported by the National Natural Science Foundation of China (81270644, 81670166, 81230013, 81530046)the Beijing Talents fund (2015000021223ZK26)+2 种基金the Major State Basic Research Development Program of China (2013CB733700)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001)supported by the Collaborative Innovation Center of Hematology, China
文摘The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD） （HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.
基金supported by the National Natural Science Foundation of China(81530046,81270644,81230013)the Major State Basic Research Development Program of China(2013CB733700)+2 种基金the Collaborative Innovation Center of Hematology,Peking University,China,Beijing Talents fund(2015000021223ZK26)the Milstein Medical Asian American Partnership(MMAAP)Foundation Research Project Award in Hematologyproject TG-2015-003 supported by the Health Science Promotion Project of Beijing
文摘The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation(HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival after HBMT versus haploidentical rhG-CSF-mobilized peripheral blood stem cell transplantation(HPBSCT) for acute leukemia(AL) not in remission(NR) or in more than the second complete remission(>CR2). To test the hypothesis that HBMT is still superior to HPBSCT for patients with AL, multiple myeloma(MM), or non-Hodgkin lymphoma(NHL) in CR1/CR2 and for patients with chronic myeloid leukemia in the first and second chronic phase lacking a matched donor, we designed a propensity score method-based multicenter study.Hematopoietic recovery, acute graft-versus-host disease(aGVHD), and chronic GVHD were comparable between the HBMT group(n=168) and the HPBSCT group(n=42). No significant differences were found in non-relapse mortality rate(20.17%±3.58%and 27.24%±7.16%, P=0.18) or relapse rate(19.96%±3.72% and 28.49%±8.25%, P=0.32) between the HBMT group and the HPBSCT group. HBMT recipients had better overall survival(65.0%±4.2% and 54.2%±8.3%, P=0.037) and disease-free survival(59.9%±4.6% and 44.3%±8.7%, P=0.051). Multivariate analysis showed that HPBSCT was associated with poorer DFS(HR(95%CI), 1.639(0.995–2.699), P=0.052). Our comparisons showed that HBMT was superior to HPBSCT as a post-remission treatment for patients lacking an identical donor.
基金by grants from the National Key Research and Development Program of China(2017YFA0104500)the National Natural Science Foundation of China(81471525,31671244,and 31872734,Q.G.+2 种基金81601975,K.Z.)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT31039).
文摘Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period.Regulatory T cells(Tregs)are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses.The features of Tregs in the neonatal liver under steady-state conditions are not well understood.The present study aimed to investigate the phenotype,functions,and significance of neonatal Tregs in the liver.We found a wave of thymus-derived Treg influx into the liver during 1–2 weeks of age.Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder.More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation,and the liver Tregs acquired stronger suppressive functions.The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARγand T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses.The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.
基金Beijing Natural Science Foundation(No.H2018206423)National Natural Science Foundation of China(No.81970113)+1 种基金Key Program of National Natural Science Foundation of China(No.81730004)National Key Research and Development Program of China(No.2017YFA0105503)。
文摘Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA.We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia(ITP)patients.Methods:This prospective,open-label,observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China.The study evaluated response rates and platelet counts at different time points after the switch,bleeding events,time to response,duration of response,and adverse events.Results:At 6 weeks after switching,response was observed in 21/49 patients(43%)who switched for inefficacy and 34/47 patients(72%)who switched for non-efficacy-related issues.In the inefficacy group,9/27 patients(33%)responded to eltrombopag,and 12/22 patients(55%)responded to rh-TPO.In the non-efficacy-related group,21/26(81%)and 13/21(62%)patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching,respectively.Response at 6 months was achieved in 24/49 patients(49%)switching for inefficacy and 37/47 patients(79%)switching for non-efficacy issues.In the inefficacy group,13/27 patients(48%)responded to eltrombopag,and 11/22 patients(50%)responded to rh-TPO.In the non-efficacy-related group,22/26 patients(85%)and 15/21 patients(71%)in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching,respectively.Both eltrombopag and rh-TPO were well tolerated.Conclusions:Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA.When the switch was motivated by other reasons,including patient preference and platelet count fluctuations,the probability of response was high.Registration:ClinicalTrials.gov,NCT04214951.
基金supported by the Key Program of the National Natural Science Foundation of China(81930004)the National Key Research and Development Program of China(2022YFA1103300,2022YFC2502606)+6 种基金the Major Program of the National Natural Science Foundation of China(82293630)the National Natural Science Foundation of China(82170208)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-034,2022-I2MC&T-B-121)Peking University People’s Hospital Research and Development Funds(RZ2022-02)the Natural Science Foundation of Beijing(Z230016)Tongzhou district science and technology plan project(KJ2024CX045)the Fundamental Research Funds for Central Universities.
文摘Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRDnegative group(MRD‒_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD‒_CD8 clusters and vice versa.MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD‒_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.
基金partly supported by grants from the National Key Research and Development Program of China(2017YFA0104500)National Natural Science Foundation of China(81670168)the Key Program of National Natural Science Foundation of China(81230013)。
文摘Acute graft-versus-host disease(a GVHD)is caused by allo-activated donor T cells infiltrating target organs.As a regulator of immune function,granulocyte colony-stimulating factor(G-CSF)has been demonstrated to relieve the a GVHD reaction.However,the role of G-CSF-primed donor Tcells in specific target organs is still unknown.In this study,we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c)and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group.This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model,especially in the lung and gut.Moreover,we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs.In addition,G-CSF treatment inhibited inducible co-stimulator(ICOS)expression and increased the expression of tolerance-related genes in recipient mice.Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD,especially for its precise regulation in GVHD target organs.
基金supported by the National High Technology Research and Development Program of China (2013AA020401)the National Natural Science Foundation of China (81470342)
文摘Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9%vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001).The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%,respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions(P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.
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.
基金supported by grants from the National Natural Science Foundation of China(Nos.82070184 and 82270228)sponsored by Beijing Nova Program(No.20220484235)Peking University People’s Hospital Research and Development Funds(No.RDL2021-01)
文摘To the Editor:For recipients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),allogeneic hematopoietic stem cell transplantation(allo-HSCT)often fails to provide them with a satisfactory prognosis.The chimeric antigen receptor T(CAR-T)cells are proven to be safe and effective for these patients.[1]But there are few published studies assessing the advantages of CAR-T compared to traditional chemotherapy as a bridging treatment followed by HSCT.Consequently,we conducted this study to confirm whether children and young adult R/R B-ALL patients with CAR-T therapy could expect a better post-HSCT prognosis,compared to R/R patients only receiving traditional chemotherapy before transplantation.
基金supported by grants from National Natural Science Foundation of China(Nos.81870140 and 82070184)Peking University People’s Hospital Research and Development Funds(No.RDL2021-01)+1 种基金Beijing Nova Program(No.20220484235)Beijing Life Oasis Public Service Center(No.CARTFR-01)
文摘Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.
文摘To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution （IR） in 144 patients who received allogeneic stem ceil transplantation （alio- SCT） and without showing any of the following events： poor graft function, grades II-IV acute graft-versus-host disease （GVHD）, serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3~ T cells, CD8~ T cells, and CD19~ B cells, and very slow in CD4~ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune ceils need not reach those in healthy donor in the first year after transplantation. We suggest that data from this recipient cohort should be used as reference values for post-transplant immune ceil counts in patients receiving HSCT.
基金supported by National Key Research and Development Program of China(No.2017YFA0105503)National Natural Science Foundation of China(Nos.81970113 and 81800116)+1 种基金Key Program of National Natural Science Foundation of China(No.81730004)Beijing Natural Science Foundation(No.H2018206423).
文摘Skin and soft tissue infections(SSTIs)refer to infections involving the skin,subcutaneous tissue,fascia,and muscle.In transplant populations with hematological malignancies,an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly.However,to date,the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation(HSCT)patients remain unclear.This study included 228 patients(3.67%)who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital.The overall annual survival rate was 71.5%.We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure(PPGF),comorbidities of acute kidney injury(AKI),and hospital-acquired pneumonia(HAP)were independent risk factors for death in the study population.A PPGF-AKI-HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP.The areas under the curves of internal and external validation were 0.833(95%CI 0.760–0.906)and 0.826(95%CI 0.715–0.937),respectively.The calibration plot revealed the high consistency of the estimated risks,and decision curve analysis showed considerable net benefits for patients.
