BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences rela...BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.展开更多
Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Wi...Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.展开更多
We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic ste...We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.展开更多
BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inc...BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.展开更多
To study the effect of natural killer (NK) cells on graft-versus-host disease (GVHD) after H-2 haploidentical bone marrow transplantation (BMT) in mice. Methods :Murine model of H-2 haploidentical BMT was estab...To study the effect of natural killer (NK) cells on graft-versus-host disease (GVHD) after H-2 haploidentical bone marrow transplantation (BMT) in mice. Methods :Murine model of H-2 haploidentical BMT was established by using Balb/c (H- 2d) mouse as recipient, and Balb/c (H-2d)×C57BL/6 (H-2b) (H-2db) mouse as donor. Lethally irradiated Balb/c (H-2d) mice were transplanted with the bone marrow cells from Balb/c(H-2d)×C57BL/6(H-2b) (H-2db) mice containing donor spleen cells and/or NK cells. GVHD and survival rates were studied by observation of clinical manifestations and pathological changes. Results:In the group of bone marrow +spleen cells, GVHD was induced in 90% mice; but in the group plus with low amount of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high amount of NK cells, GVHD was induced only in 10% mice. Compared to the group transplanted only with BM plus spleen cells, the incidences of GVHD in the latter two groups decreased significantly (P 〈 0.01) and the survival rates at different periods of 15, 30, 45 and 60 days increased obviously (P 〈 0.01). Conclusion: In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate.展开更多
Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods T...Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time展开更多
Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction ...Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty - nine cases of AML in first relapse after complete remission by standard DA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
A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to ident...A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.展开更多
Allogeneic hematopoietic stem cell transplantation .(allo-HSCT) is one of the best, or even the only,option for the cure of leukemia, especially for patients with high risk factors . However, it is limited by the sh...Allogeneic hematopoietic stem cell transplantation .(allo-HSCT) is one of the best, or even the only,option for the cure of leukemia, especially for patients with high risk factors . However, it is limited by the shortage of suitable donors, because only 25%-30% patients can find a human leukocyte antigen (HLA)-identical sibling donor. Although much progress has been made in finding a suitable unrelated donor or unrelated cord blood (uCB) due to the expansion of the worldwide unrelated donor program,展开更多
Background In haploidentical hematopoietic stem cell transplantation (HSCT), the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor o...Background In haploidentical hematopoietic stem cell transplantation (HSCT), the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia (GVL) effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for 〈6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for 〈6 weeks. Results First, compared with prophylaxis for 〈6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6% vs. 69.0%, P 〈0.001). Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P 〈0.001). Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P 〈0.05), reduced the therapeutic application of immunosuppressive agents (P=0.019), but increased the incidence of chronic GVHD (P〈0.05). Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P 〈0.05). Conclusions In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for 〈6 weeks. This strategy will probably improve the safety and efficacy of modified DLI further.展开更多
This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone M...This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.展开更多
Background:Human leukocyte antigen-identical sibling donor(ISD)-hematopoietic stem cell transplantation(SCT)is a potentially curative treatment for high-risk pediatric acute myeloid leukemia(AML).A haploidentical dono...Background:Human leukocyte antigen-identical sibling donor(ISD)-hematopoietic stem cell transplantation(SCT)is a potentially curative treatment for high-risk pediatric acute myeloid leukemia(AML).A haploidentical donor(HID)is readily available to almost all children.Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML.However,the role of HID-SCT in high-risk pediatric AML is unclear.Methods:To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT,we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT(n=23)or HID-SCT(n=156).Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT.We also analyzed the subgroup data of AML patients at first complete remission(CR1)before SCT with known cytogenetic risk.Results:The numbers of adverse cytogenetic risk recipients were 8(34.8%)and 13(18.8%)in the ISD-SCT group and the HID-SCT group,and the number of patients with disease status beyond CR1 were 6(26.1%)and 14(20.3%)in the two groups.The cumulative rates of grades II-IV acute graft-versus-host disease(GVHD)were 13.0%in the ISD-SCT group and 34.8%in the HID-SCT group(P=0.062),with a three-year cumulative rates of chronic GVHD at 14.1%and 34.9%,respectively(P=0.091).The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group(39.1%vs.16.4%,P=0.027);with non-relapse mortality at 0.0%and 10.6%(P=0.113),respectively.The three-year overall survival rates were 73.0%for the ISD-SCT group and 74.6%for the HID-SCT group(P=0.689).In subgroup analysis,the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group(50.0%vs.9.2%,P=0.001)and the three-year DFS in the ISD-SCT group(50.0%)was lower than that in the HID-SCT group(81.2%)(P=0.021).Conclusions:Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.展开更多
Background: Studies of haploidentical-related donor (HRD) stem cell transplantation using a combination of peripheral blood stem cells (PBSCs) and bone marrow as the graft have reported encouraging results for pa...Background: Studies of haploidentical-related donor (HRD) stem cell transplantation using a combination of peripheral blood stem cells (PBSCs) and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia (AML). Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation (HRD-PBSCT) for relapsed/refractory AML were analyzed. Methods: We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs (n = 36). Results: Thirty-one (86.1%) patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease (aGVHD) in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation (range: 10-1700 days), reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age 〉40 years were independent risk factors for inferior disease-free survival or overall survival (P 〈 0.05). The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions: Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.展开更多
Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vit...Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).展开更多
Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr...Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr virus infection(CAEBV).Methods Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital,Capital Medical University,from October 2016 to June 2020 were analyzed retrospectively.Data relating to the clinical manifestations,engraftment,and prognosis of the children were extracted from medical records.Results Twenty-five patients,including 16 males and 9 females,with an onset age of 5.0±2.6 years and a transplantation age of 6.9±2.9 years,were enrolled irnhis study.The mean time from diagnosis to transplantation was 3.8(2.0-40.2)months.The mean observation time was 19.0±12.0 months.Three patients received the reduced intensity conditioning regimen,and the remaining patients all received the modified myeloablative conditioning regimen.By the end of the follow-up,23 patients were characterized by disease-free survival(DFS),22 were characterized by event-free survival(EFS).and two died.One of the patients died of thrombotic microangiopathy(TMA),and another died of graft versus host disease(GVHD);this patient discontinued the treatment for economic reasons.The 3-year overall survival(OS)rate was estimated to be 92.0%±5.4%,and the 3-year EFS rate was estimated to be 87.4%±6.8%.All active patients survived after HSCT event-free.Acute GVHD degrees 1-3 were observed in ten patients(40.0%),and degree IV was observed in six(24.0%),who were all cured except for one patient.Chronic GVHD was observed in nine(36.0%),and most of these cases were mild.The incidence of TMA and veno-occlusive disease(VOD)was 28.0%and 4.0%.Conclusions Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation.Patients with active disease before HSCT also benefited from haplo-HSCT.Haplo-HSCT requires careful monitoring for complications,such as GVHD and TMA.Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.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
Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients ...Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients lacking a human leukocyte antigen(HLA)-matched donor.This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II.Twenty-two patients were included and followed up,and FLU/BU/CY/ATG was used as conditioning regimen.Among these patients,21 were successfully engrafted,19 of whom survived after haplo-BMT.Four patients experienced grade II–IV aGvHD,including two with grade III–IV aGvHD.Six patients experienced chronic GvHD,among whom four were mild and two were moderate.Twelve patients experienced infections during BMT.One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease,and both recovered after rituximab infusion.Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73%after a median follow-up of 42 months,indicating its effectiveness as a salvage therapy.These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.展开更多
Importance: Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only curative treatment for familial hemophagocytic lymphohistiocytosis (FHLH). Treatment of pediatric FHLH with reduced-in...Importance: Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only curative treatment for familial hemophagocytic lymphohistiocytosis (FHLH). Treatment of pediatric FHLH with reduced-intensity conditioning (RIC)-based haploidentical donor (HID) HSCT has been rarely reported. Objective: To investigate outcomes and adverse events in patients with FHLH who received HID-HSCT. Methods: We conducted a retrospective study of five patients, including three with mutations in PRF1 and two with XIAP deficiency. Four of the five donors were heterozygous for these mutations. The conditioning regimen included fludarabine, cyclophosphamide, and antithymocyte globulin, with or without low-dose irradiation. Unmanipulated mobilized bone marrow and peripheral blood stem cells were used as the grafts. results: All five patients were successfully engrafted. Four patients survived, and one patient died. All exhibited complete response (CR) after HSCT. All of the patients who survived exhibited CR to FHLH without severe regimen-related complications at a median of 29.5 months (range: 23–34 months) after HSCT. Four of the five patients had mixed donor chimerism. Three patients had 17% to 87% mixed donor chimerism but remained free of disease. Four patients received donor lymphocyte infusion (DLI), which improved the level of mixed donor chimerism. One patient experienced a decrease in donor chimerism to 1% and relapsed;Four patients developed acute graft-versus-host disease (GvHD) (grade I or II), and one patient developed grade IV GvHD. Interpretation: HID-HSCT with RIC can be considered for treatment for patients with FHLH, but the conditions and DLI regimens need to be optimized for long-term use, and more prospective studies should be conducted.展开更多
We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT)(n = 332). PSCs were observed in 61 ...We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT)(n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group;19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens .展开更多
文摘BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.
文摘Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.
基金This work was supported by the National Key Research and Development Program of China(2017YFA0104500)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)+6 种基金the Key Program of the National Natural Science Foundation of China(81930004)Capital’s Funds for Health Improvement and Research(2018-4-4089)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-034)the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)Peking University Clinical Scientist Program(BMU2019LCKXJ003)supported by the Fundamental Research Funds for the Central Universities.
文摘We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.
基金Supported by The Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine,No.2017ZA129 and No.2018ZA112.
文摘BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.
文摘To study the effect of natural killer (NK) cells on graft-versus-host disease (GVHD) after H-2 haploidentical bone marrow transplantation (BMT) in mice. Methods :Murine model of H-2 haploidentical BMT was established by using Balb/c (H- 2d) mouse as recipient, and Balb/c (H-2d)×C57BL/6 (H-2b) (H-2db) mouse as donor. Lethally irradiated Balb/c (H-2d) mice were transplanted with the bone marrow cells from Balb/c(H-2d)×C57BL/6(H-2b) (H-2db) mice containing donor spleen cells and/or NK cells. GVHD and survival rates were studied by observation of clinical manifestations and pathological changes. Results:In the group of bone marrow +spleen cells, GVHD was induced in 90% mice; but in the group plus with low amount of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high amount of NK cells, GVHD was induced only in 10% mice. Compared to the group transplanted only with BM plus spleen cells, the incidences of GVHD in the latter two groups decreased significantly (P 〈 0.01) and the survival rates at different periods of 15, 30, 45 and 60 days increased obviously (P 〈 0.01). Conclusion: In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate.
文摘Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time
文摘Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty - nine cases of AML in first relapse after complete remission by standard DA
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 Beijing Talents Fund(2015000021223ZK39)the Capital’s Funds for Health Improvement and Research(2018-4-4089)+3 种基金the Key Program of the National Natural Science Foundation of China(81530046)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou city(201704020214)
文摘A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.
文摘Allogeneic hematopoietic stem cell transplantation .(allo-HSCT) is one of the best, or even the only,option for the cure of leukemia, especially for patients with high risk factors . However, it is limited by the shortage of suitable donors, because only 25%-30% patients can find a human leukocyte antigen (HLA)-identical sibling donor. Although much progress has been made in finding a suitable unrelated donor or unrelated cord blood (uCB) due to the expansion of the worldwide unrelated donor program,
文摘Background In haploidentical hematopoietic stem cell transplantation (HSCT), the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia (GVL) effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for 〈6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for 〈6 weeks. Results First, compared with prophylaxis for 〈6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6% vs. 69.0%, P 〈0.001). Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P 〈0.001). Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P 〈0.05), reduced the therapeutic application of immunosuppressive agents (P=0.019), but increased the incidence of chronic GVHD (P〈0.05). Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P 〈0.05). Conclusions In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for 〈6 weeks. This strategy will probably improve the safety and efficacy of modified DLI further.
基金This work was 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 compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.
基金This work was partly supported by grants from the National Key Research and Development Program of China(Grant No.:2017YFA0104500)from the Ministry of Science and TechnologyNational Natural Science Foundation of China(Grant No.:81770189,81621001,and 81530046)+3 种基金the Science and Technology Project of Guangdong Province of China(Grant No.:2016B030230003)Peking University Clinical Scientist Program(Grant No.:BMU2019LCKXJ003)the Fundamental Research Funds for the Central Universitiesthe project of health collaborative innovation of Guangzhou city(Grant No.:201704020214).
文摘Background:Human leukocyte antigen-identical sibling donor(ISD)-hematopoietic stem cell transplantation(SCT)is a potentially curative treatment for high-risk pediatric acute myeloid leukemia(AML).A haploidentical donor(HID)is readily available to almost all children.Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML.However,the role of HID-SCT in high-risk pediatric AML is unclear.Methods:To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT,we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT(n=23)or HID-SCT(n=156).Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT.We also analyzed the subgroup data of AML patients at first complete remission(CR1)before SCT with known cytogenetic risk.Results:The numbers of adverse cytogenetic risk recipients were 8(34.8%)and 13(18.8%)in the ISD-SCT group and the HID-SCT group,and the number of patients with disease status beyond CR1 were 6(26.1%)and 14(20.3%)in the two groups.The cumulative rates of grades II-IV acute graft-versus-host disease(GVHD)were 13.0%in the ISD-SCT group and 34.8%in the HID-SCT group(P=0.062),with a three-year cumulative rates of chronic GVHD at 14.1%and 34.9%,respectively(P=0.091).The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group(39.1%vs.16.4%,P=0.027);with non-relapse mortality at 0.0%and 10.6%(P=0.113),respectively.The three-year overall survival rates were 73.0%for the ISD-SCT group and 74.6%for the HID-SCT group(P=0.689).In subgroup analysis,the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group(50.0%vs.9.2%,P=0.001)and the three-year DFS in the ISD-SCT group(50.0%)was lower than that in the HID-SCT group(81.2%)(P=0.021).Conclusions:Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.
基金This work was partially supported by grants from the Beijing Nova Program (2011114), the National Natural Science Foundation of China (No. 30800482, 30971297, 81102242, 81000221, 81270610, 81470010, 81170518, 81370666, and 90919044), the Beijing Natural Science Foundation of China (No. 7102147, 7172200, and 7132217), the High and New Technology Program of the PLA (2010gxjs091), the Capital Medical Development Scientific Research Fund (No. 2007-2040), the National Public Health Grand Research Foundation (No 201202017), the Public Health Project (Z111 10706731 1070), and the National 973 Project of China (No. 2005CB522400).
文摘Background: Studies of haploidentical-related donor (HRD) stem cell transplantation using a combination of peripheral blood stem cells (PBSCs) and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia (AML). Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation (HRD-PBSCT) for relapsed/refractory AML were analyzed. Methods: We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs (n = 36). Results: Thirty-one (86.1%) patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease (aGVHD) in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation (range: 10-1700 days), reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age 〉40 years were independent risk factors for inferior disease-free survival or overall survival (P 〈 0.05). The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions: Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.
文摘Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).
文摘Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr virus infection(CAEBV).Methods Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital,Capital Medical University,from October 2016 to June 2020 were analyzed retrospectively.Data relating to the clinical manifestations,engraftment,and prognosis of the children were extracted from medical records.Results Twenty-five patients,including 16 males and 9 females,with an onset age of 5.0±2.6 years and a transplantation age of 6.9±2.9 years,were enrolled irnhis study.The mean time from diagnosis to transplantation was 3.8(2.0-40.2)months.The mean observation time was 19.0±12.0 months.Three patients received the reduced intensity conditioning regimen,and the remaining patients all received the modified myeloablative conditioning regimen.By the end of the follow-up,23 patients were characterized by disease-free survival(DFS),22 were characterized by event-free survival(EFS).and two died.One of the patients died of thrombotic microangiopathy(TMA),and another died of graft versus host disease(GVHD);this patient discontinued the treatment for economic reasons.The 3-year overall survival(OS)rate was estimated to be 92.0%±5.4%,and the 3-year EFS rate was estimated to be 87.4%±6.8%.All active patients survived after HSCT event-free.Acute GVHD degrees 1-3 were observed in ten patients(40.0%),and degree IV was observed in six(24.0%),who were all cured except for one patient.Chronic GVHD was observed in nine(36.0%),and most of these cases were mild.The incidence of TMA and veno-occlusive disease(VOD)was 28.0%and 4.0%.Conclusions Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation.Patients with active disease before HSCT also benefited from haplo-HSCT.Haplo-HSCT requires careful monitoring for complications,such as GVHD and TMA.Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.
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.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81570124 to Jinsong Yan,No.81702683 to Jiajun Xie,No.81773389 to Jing Shao)Science and Technology Innovation Leading Talent Program of Liaoning Province(No.XLYC1902036 to Jinsong Yan)+5 种基金Basic Research on the Application of Dalian Innovation Fund(No.2019J12SN56 to Jinsong Yan)Key R&D projects in Liaoning Province(No.2019JH8/10300027 to Jinsong Yan)Key Project of the Educational Department of Liaoning Province(No.LZ2020003 to Jinsong Yan)the Capital Health Research and Development of Special Project(No.2014-2-5122 to Hengxiang Wang)the Beijing Municipal Science and Technology Project(No.Z151100004015016 to Hengxiang Wang)the Dalian Medical Scientific Research Project(No.1712040 to Yan Yang)。
文摘Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients lacking a human leukocyte antigen(HLA)-matched donor.This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II.Twenty-two patients were included and followed up,and FLU/BU/CY/ATG was used as conditioning regimen.Among these patients,21 were successfully engrafted,19 of whom survived after haplo-BMT.Four patients experienced grade II–IV aGvHD,including two with grade III–IV aGvHD.Six patients experienced chronic GvHD,among whom four were mild and two were moderate.Twelve patients experienced infections during BMT.One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease,and both recovered after rituximab infusion.Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73%after a median follow-up of 42 months,indicating its effectiveness as a salvage therapy.These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.
文摘Importance: Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only curative treatment for familial hemophagocytic lymphohistiocytosis (FHLH). Treatment of pediatric FHLH with reduced-intensity conditioning (RIC)-based haploidentical donor (HID) HSCT has been rarely reported. Objective: To investigate outcomes and adverse events in patients with FHLH who received HID-HSCT. Methods: We conducted a retrospective study of five patients, including three with mutations in PRF1 and two with XIAP deficiency. Four of the five donors were heterozygous for these mutations. The conditioning regimen included fludarabine, cyclophosphamide, and antithymocyte globulin, with or without low-dose irradiation. Unmanipulated mobilized bone marrow and peripheral blood stem cells were used as the grafts. results: All five patients were successfully engrafted. Four patients survived, and one patient died. All exhibited complete response (CR) after HSCT. All of the patients who survived exhibited CR to FHLH without severe regimen-related complications at a median of 29.5 months (range: 23–34 months) after HSCT. Four of the five patients had mixed donor chimerism. Three patients had 17% to 87% mixed donor chimerism but remained free of disease. Four patients received donor lymphocyte infusion (DLI), which improved the level of mixed donor chimerism. One patient experienced a decrease in donor chimerism to 1% and relapsed;Four patients developed acute graft-versus-host disease (GvHD) (grade I or II), and one patient developed grade IV GvHD. Interpretation: HID-HSCT with RIC can be considered for treatment for patients with FHLH, but the conditions and DLI regimens need to be optimized for long-term use, and more prospective studies should be conducted.
基金This work was supported by the National Natural Science Foundation of China (No. 81802070)China Postdoctoral Science Foundation (No. 2018M631280)+4 种基金the CapitaFs Funds for Health Improvement and Research (No. 2018-4-4089)the Key Program of the National Natural Science Foundation of China (No. 81530046)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001)the Science and Technology Project of the Guangdong Province of China (No. 2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City (No. 201704020214).
文摘We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT)(n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group;19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens .