Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after ...Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.展开更多
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
Background AIIogeneic peripheral blood stem cell transplantation from unrelated donors （UR-PBSCT） is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen （HLA）-identical si...Background AIIogeneic peripheral blood stem cell transplantation from unrelated donors （UR-PBSCT） is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen （HLA）-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT. Methods Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups. Results One hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor （10/10）, 36 of them with a one locus mismatched donor （9/10）, and 15 of them with a two loci mismatched donor （8/10）. Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups （P〉0.05）. Two-year cumulative incidence of relapse, overall survival （OS） and disease-free survival （DFS） among those three groups were similar （P〉0.05）. The cumulative incidence of 100-day Ill-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group （3.3%, 8.6%, and 26.7%, P=0.009）. The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups （26.67%, 52.78%, and 41.18%, P=0.035）. The cumulative incidence of 100-day and 2-year transplantation related mortality （TRM） in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, （8.4%, 11.8% and 33.3%, P=0.016） and （12.3%, 18.7% and 47.5%, P=0.002）. Conclusions HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM. Chin Med J 2014;127 （14）： 2612-2617展开更多
Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA chi...Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015.According to the source of donor,the展开更多
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
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 efficacy of salvage interferon-α(IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI)(n=24). Patients who did not ...The efficacy of salvage interferon-α(IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI)(n=24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.展开更多
Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the ...Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49.1%, P=0.000）, although the rates of whole cGVHD were not significantly different （30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively）. The patients had a similar rate of CMV infection （21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively）, while the HC occurrence was lower after UCBT （7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively）. As of August 2012, there was no apparent difference in 5-year overall survival （OS）, LFS, or the relapse rate for each graft source （52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT）. Conclusion These data support the use of UCB donors as an alternative allogeneic donor.展开更多
This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT ...This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December 2017.Forty-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method(1:4).Primary graft failure including poor graft function and graft rejection did not occur in two groups.In BM hypoplasia and hyperplasia groups,the cumulative incidence(CI)of neutrophil engraftment at day 28(91.7%vs.93.8%,P=0.75),platelet engraftment at day 150(83.3%vs.93.8%,P=0.48),the median time to myeloid engraftment(14 days vs.14 days,P=0.85)and platelet engraftment(14 days vs.14 days,P=0.85)were comparable.The 3-year progression-free survival,overall survival,CI of non-relapse mortality and relapse were 67.8%vs.71.7%(P=0.98),69.8%vs.77.8%(P=0.69),18.5%vs.13.6%(P=0.66),and 10.2%vs.10.4%(P=0.82),respectively.In multivariate analysis,donor BM hypoplasia did not affect patient clinical outcomes after allo-HSCT.If patients have no other suitable donor,a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.展开更多
Objective To analyze allele mismatches of HLA-A,-B,-C,-DRB1,-DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit.Methods 230...Objective To analyze allele mismatches of HLA-A,-B,-C,-DRB1,-DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit.Methods 230 pairs of donor-recipient were performed HLA-A,B,C,DRB1,DQB1 typing using展开更多
Allogeneic hematopoietic stem cell transplantation （alIo-HSCT） has three decades history in China. During these periods, the number of HSCT has been increasing, donor and stem cell sources were expanded, indication ...Allogeneic hematopoietic stem cell transplantation （alIo-HSCT） has three decades history in China. During these periods, the number of HSCT has been increasing, donor and stem cell sources were expanded, indication of diseases and patients for HSCT extended. Forty-two HSCT units offered their data 1-6 times from July 2007 to June 2010. The annual increase rates were 8.8% to 10.8%. Matched sibling donor is 41%, mismatched related/haploidentical donor is 24%, unrelated volunteer donor is 16%, and umbilical cord blood is 2%. The indications of major disease entities are acute myeloid leukemia （AML, 35%）, acute lymphobastic leukemia （ALL, 25%）, chronic myeloid leukemia （CML, 21%）, and myelodysplastic syndrome （MDS, 8%）. The different opinions on the indication of HSCT were supported by some trials, matched/haploidentical HSCT fit for middle or high risk ALL and AML in first complete remission （CR1）, the international prognosis score system （IPSS） -- middle-II/high risk MDS, CML in advanced stage and so on, when patients have no matched sibling donor. In the Peking University Institute of Hematology, Peking University People＇s Hospital, haploidentical HSCT has received a comparable result to matched simbling donor HSCT and unrelated matched donor HSCT; we suggest haploidentical donor might be a routine alternative donor for high-risk patents who need an urgent HSCT without matched related donor in soecial center.展开更多
Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilic...Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilical-cord blood transplantation (UCBT) in adult patients, particularly in those with high body weight. We hypothesized that the combined transplantation of two partially matched UCB units would improve engraftment without crossed immunological rejection. Since May 2000, six adult patients with high risk leukemia have been transplanted in this study.展开更多
The efficacy of minimal residual disease (MRD)-directed immunotherapy,including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI),...The efficacy of minimal residual disease (MRD)-directed immunotherapy,including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI),was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT).High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after ailo-HSCT were studied (n =47).The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample.The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P=0.377)and 9.1% and 0.0% (P=0.985) for patients in the IFN-α and chemo-DLI groups,respectively.The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P =0.891) and 84.3% and 84.6% (P=0.972) for patients in the IFN-α and chemo-DLI groups,respectively.Persistent MRD after immunotherapy was associated with poor survival.Thus,the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after alIo-HSCT,and the efficacy was comparable between chemo-DLI and IFN-α treatment.展开更多
Allogeneic hematopoietic stem cell transplantation(HSCT)is one of the most effective options for hematological malignancies,and human leukocyte antigen-partially matched related donors(PMRDs)are a valuable option for ...Allogeneic hematopoietic stem cell transplantation(HSCT)is one of the most effective options for hematological malignancies,and human leukocyte antigen-partially matched related donors(PMRDs)are a valuable option for HSCT.Several protocols(with or without ex vivo T-cell depletion(TCD))have been established worldwide.TCD including CD34+positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity.However,TCD is associated with prolonged immune deficiencies,increased risks of infectious complications,and high transplantation-related mortality.PMRD HSCT without ex vivo TCD is well developed,and numerous patients have benefitted from it.Here,we review the literature on PMRD HSCT.展开更多
文摘Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.
文摘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.
文摘Background AIIogeneic peripheral blood stem cell transplantation from unrelated donors （UR-PBSCT） is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen （HLA）-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT. Methods Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups. Results One hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor （10/10）, 36 of them with a one locus mismatched donor （9/10）, and 15 of them with a two loci mismatched donor （8/10）. Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups （P〉0.05）. Two-year cumulative incidence of relapse, overall survival （OS） and disease-free survival （DFS） among those three groups were similar （P〉0.05）. The cumulative incidence of 100-day Ill-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group （3.3%, 8.6%, and 26.7%, P=0.009）. The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups （26.67%, 52.78%, and 41.18%, P=0.035）. The cumulative incidence of 100-day and 2-year transplantation related mortality （TRM） in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, （8.4%, 11.8% and 33.3%, P=0.016） and （12.3%, 18.7% and 47.5%, P=0.002）. Conclusions HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM. Chin Med J 2014;127 （14）： 2612-2617
文摘Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015.According to the source of donor,the
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.
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the National Natural Science Foundation of China (No.81400145)the Beijing Talents Fund (No.2015000021223ZK39)+2 种基金the Key Program of the National Natural Science Foundation of China (No.81530046)Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No.81621001)the Science and Technology Project of Guangdong Province of China (No.2016B030230003).
文摘The efficacy of salvage interferon-α(IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI)(n=24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.
文摘Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49.1%, P=0.000）, although the rates of whole cGVHD were not significantly different （30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively）. The patients had a similar rate of CMV infection （21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively）, while the HC occurrence was lower after UCBT （7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively）. As of August 2012, there was no apparent difference in 5-year overall survival （OS）, LFS, or the relapse rate for each graft source （52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT）. Conclusion These data support the use of UCB donors as an alternative allogeneic donor.
基金supported by the National Natural Science Foundation of China(81670167)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)sponsored by the Fund for Fostering Young Scholars of Peking University Health Science Center(BMU2017PY010)
文摘This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December 2017.Forty-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method(1:4).Primary graft failure including poor graft function and graft rejection did not occur in two groups.In BM hypoplasia and hyperplasia groups,the cumulative incidence(CI)of neutrophil engraftment at day 28(91.7%vs.93.8%,P=0.75),platelet engraftment at day 150(83.3%vs.93.8%,P=0.48),the median time to myeloid engraftment(14 days vs.14 days,P=0.85)and platelet engraftment(14 days vs.14 days,P=0.85)were comparable.The 3-year progression-free survival,overall survival,CI of non-relapse mortality and relapse were 67.8%vs.71.7%(P=0.98),69.8%vs.77.8%(P=0.69),18.5%vs.13.6%(P=0.66),and 10.2%vs.10.4%(P=0.82),respectively.In multivariate analysis,donor BM hypoplasia did not affect patient clinical outcomes after allo-HSCT.If patients have no other suitable donor,a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.
文摘Objective To analyze allele mismatches of HLA-A,-B,-C,-DRB1,-DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit.Methods 230 pairs of donor-recipient were performed HLA-A,B,C,DRB1,DQB1 typing using
文摘Allogeneic hematopoietic stem cell transplantation （alIo-HSCT） has three decades history in China. During these periods, the number of HSCT has been increasing, donor and stem cell sources were expanded, indication of diseases and patients for HSCT extended. Forty-two HSCT units offered their data 1-6 times from July 2007 to June 2010. The annual increase rates were 8.8% to 10.8%. Matched sibling donor is 41%, mismatched related/haploidentical donor is 24%, unrelated volunteer donor is 16%, and umbilical cord blood is 2%. The indications of major disease entities are acute myeloid leukemia （AML, 35%）, acute lymphobastic leukemia （ALL, 25%）, chronic myeloid leukemia （CML, 21%）, and myelodysplastic syndrome （MDS, 8%）. The different opinions on the indication of HSCT were supported by some trials, matched/haploidentical HSCT fit for middle or high risk ALL and AML in first complete remission （CR1）, the international prognosis score system （IPSS） -- middle-II/high risk MDS, CML in advanced stage and so on, when patients have no matched sibling donor. In the Peking University Institute of Hematology, Peking University People＇s Hospital, haploidentical HSCT has received a comparable result to matched simbling donor HSCT and unrelated matched donor HSCT; we suggest haploidentical donor might be a routine alternative donor for high-risk patents who need an urgent HSCT without matched related donor in soecial center.
文摘Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilical-cord blood transplantation (UCBT) in adult patients, particularly in those with high body weight. We hypothesized that the combined transplantation of two partially matched UCB units would improve engraftment without crossed immunological rejection. Since May 2000, six adult patients with high risk leukemia have been transplanted in this study.
基金Capital's Funds for Health Improvement and Research (No.2018-4-4089)the Key Program of the National Natural Science Foundation of China (No.81530046)+3 种基金Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No.81621001)the Science and Technology Project of Guangdong Province of China (No.2016B030230003)the National Science and Technology Support Program (No.2014BAI09B13)the Project of Health Collaborative Innovation of Guangzhou city (No.201704020214).
文摘The efficacy of minimal residual disease (MRD)-directed immunotherapy,including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI),was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT).High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after ailo-HSCT were studied (n =47).The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample.The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P=0.377)and 9.1% and 0.0% (P=0.985) for patients in the IFN-α and chemo-DLI groups,respectively.The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P =0.891) and 84.3% and 84.6% (P=0.972) for patients in the IFN-α and chemo-DLI groups,respectively.Persistent MRD after immunotherapy was associated with poor survival.Thus,the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after alIo-HSCT,and the efficacy was comparable between chemo-DLI and IFN-α treatment.
基金This work was partly supported by the National High Technology Research and Development Program of China(863 Program)(Grant No.2011AA020105)the Key Program of National Natural Science Foundation of China(Grant No.81230013).
文摘Allogeneic hematopoietic stem cell transplantation(HSCT)is one of the most effective options for hematological malignancies,and human leukocyte antigen-partially matched related donors(PMRDs)are a valuable option for HSCT.Several protocols(with or without ex vivo T-cell depletion(TCD))have been established worldwide.TCD including CD34+positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity.However,TCD is associated with prolonged immune deficiencies,increased risks of infectious complications,and high transplantation-related mortality.PMRD HSCT without ex vivo TCD is well developed,and numerous patients have benefitted from it.Here,we review the literature on PMRD HSCT.
