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
Stem cells have their origins in the embryo and during the process of organogenesis, these differentiate into specialized cells which mature to form tissues. In addition, stem cell are characterized by an ability to i...Stem cells have their origins in the embryo and during the process of organogenesis, these differentiate into specialized cells which mature to form tissues. In addition, stem cell are characterized by an ability to indefinitely self renew. Stem cells are broadly classified into embryonic stem cells and adult stem cells. Adult stem cells can be genetically reprogrammed to form pluripotent stem cells and exist in an embroyonic like state. In the early phase of embryogenesis, human embryonic stem cells only exist transiently. Adult stem cells are omnipresent in the body and function to regenerate during the process of apoptosis or tissue repair. Hematopoietic stem cells(HSC) are adult stem cells that form blood and immune cells. Autoimmune responses are sustained due to the perennial persistence of tissue self autoantigens and/or auto reactive lymphocytes. Immune reset is a process leading to generation of fresh self-tolerant lymphocytes after chemotherapy induced elimination of self or autoreactive lymphocytes. This forms the basis for autologous HSC transplantation(HSCT). In the beginning HSCT had been limited to refractory autoimmune rheumatic diseases(AIRD) due to concern about transplant related mortality and morbidity. However HSCT for AIRD has come a long way with better understanding of patient selection, conditioning regime and supportive care. In this narrative review we have examined the available literature regarding the HSCT use in AIRD.展开更多
AIM: To determine the incidence of and the risk factors for cytomegalovirus(CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation(ASCT).METHODS: A total of 327 consecutive non CD3...AIM: To determine the incidence of and the risk factors for cytomegalovirus(CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation(ASCT).METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome(Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin's lymphoma and Hodgkin's lymphoma. The patients who underwent an ASCT for an acute leukemia(n = 20) in the sameperiod were excluded from this analysis. CMV DNA load in the blood has been determined by polymerasechain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed.RESULTS: Overall, 36 patients(11%) required a specific antiviral treatment for a symptomatic CMV reactivation(n = 32) or an end-organ disease(n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma(16%) and myeloma patients(8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in Ig G seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplantrelated mortality was significantly higher in patients who experienced a CMV reactivation(8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pretransplant HBc Ig G seropositivity, a diagnosis of T-cell non-Hodgkin's lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy(P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pretransplant HBc Ig G seropositivity(OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell nonHodgkin's lymphoma(OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation. CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBc Ig G seropositivity and a diagnosis of T-cell non-Hodgkin's lymphoma should be considered as independent predictor factors of CMV reactivation.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
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
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
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
In order to compare the effect between haploidentical(HID) stem cell transplantation(HSCT) and matched sibling donor(MSD)stem cell transplantation for high-risk acute myeloid leukemia(AML) in first complete remission ...In order to compare the effect between haploidentical(HID) stem cell transplantation(HSCT) and matched sibling donor(MSD)stem cell transplantation for high-risk acute myeloid leukemia(AML) in first complete remission status(CR1), we retrospectively studied 170 cases who received stem cell transplantation from Jan 2008 to Jul 2015 in Peking University People's Hospital. We divided all cases into MSD group(43 cases) and HID(127 cases) group. Patients in HID and MSD group displayed similar baseline characteristics except for age distribution. There were no statistic differences for overall survival(OS), cumulative incidence of relapse, leukemia free survival(LFS), transplantation related mortality(TRM) between HID and MSD group. The 3-year OS, LFS for all patients was 63.9% and 59.7% respectively. Multivariate analysis showed that grade III-IV acute graft versus host disease(aGVHD) was an independent risk factor for treatment related mortality(HR=8.134, 95% CI:3.210–20.611, P<0.001), monosomy/complex chromosomal karyotype and white blood cell count more than 50×109 L-1 were two independent factors for relapse(HR=1.533, 95% CI: 1.040–2.260, P=0.031)(HR=1.004, 95% CI: 1.001–1.008, P=0.015).Grade III-IV aGVHD was an independent factor for mortality(HR=3.184, 95% CI: 1.718–5.902, P<0.001). These results demonstrated some risk factors for high-risk AML leukemia transplantation and indicated for AML patients in CR1 status, haplo stem cell transplantation could have the same therapeutic effect as MSD transplantation.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
To compare the efficacy of HLA6/6-matched haploidentical hematopoietic stem cell transplant(haplo-HSCT) with that of HLA3/6-matched HSCT in T-cell-replete transplants, we recruited 27 consecutive recipients from multi...To compare the efficacy of HLA6/6-matched haploidentical hematopoietic stem cell transplant(haplo-HSCT) with that of HLA3/6-matched HSCT in T-cell-replete transplants, we recruited 27 consecutive recipients from multiple centers who received HLA6/6-matched haplo-HSCT from a parent or child donor between February 2010 and May 2016. A matched-pair analysis was designed. For each recipient from the study cohort, two recipients were randomly selected from the control cohort and matched(according to patient age, patient sex, disease type, disease status, donor age, donor sex, and recipient-donor relationship). No significant differences were found in hematopoietic recovery. The incidence of grade II–IV and III–IV acute graft versus host disease was similar(18.5% vs. 31.5%, P=0.216; 11.1% vs. 9.3%, P=0.792) in the HLA6/6 and HLA3/6 groups, respectively. The3-year cumulative incidence of relapse was 14.8% and 17.0%(P=0.800). The 3-year cumulative incidence of nonrelapse mortality was 12.1% and 17.6%(P=0.751). The estimated 3-year disease-free survival was 73.1% and 65.5%(P=0.489). The estimated 3-year overall survival was 74.7% and 74.0%(P=0.946). The data suggested the efficacy and safety of the HLA6/6-and the HLA3/6-matched haplo-HSCT between parents and children are comparable. That HLA-mismatch disparity is not correlated with T-cell-replete haplo-HSCT outcome was substantiated.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Stem cells have their origins in the embryo and during the process of organogenesis, these differentiate into specialized cells which mature to form tissues. In addition, stem cell are characterized by an ability to indefinitely self renew. Stem cells are broadly classified into embryonic stem cells and adult stem cells. Adult stem cells can be genetically reprogrammed to form pluripotent stem cells and exist in an embroyonic like state. In the early phase of embryogenesis, human embryonic stem cells only exist transiently. Adult stem cells are omnipresent in the body and function to regenerate during the process of apoptosis or tissue repair. Hematopoietic stem cells(HSC) are adult stem cells that form blood and immune cells. Autoimmune responses are sustained due to the perennial persistence of tissue self autoantigens and/or auto reactive lymphocytes. Immune reset is a process leading to generation of fresh self-tolerant lymphocytes after chemotherapy induced elimination of self or autoreactive lymphocytes. This forms the basis for autologous HSC transplantation(HSCT). In the beginning HSCT had been limited to refractory autoimmune rheumatic diseases(AIRD) due to concern about transplant related mortality and morbidity. However HSCT for AIRD has come a long way with better understanding of patient selection, conditioning regime and supportive care. In this narrative review we have examined the available literature regarding the HSCT use in AIRD.
文摘AIM: To determine the incidence of and the risk factors for cytomegalovirus(CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation(ASCT).METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome(Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin's lymphoma and Hodgkin's lymphoma. The patients who underwent an ASCT for an acute leukemia(n = 20) in the sameperiod were excluded from this analysis. CMV DNA load in the blood has been determined by polymerasechain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed.RESULTS: Overall, 36 patients(11%) required a specific antiviral treatment for a symptomatic CMV reactivation(n = 32) or an end-organ disease(n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma(16%) and myeloma patients(8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in Ig G seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplantrelated mortality was significantly higher in patients who experienced a CMV reactivation(8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pretransplant HBc Ig G seropositivity, a diagnosis of T-cell non-Hodgkin's lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy(P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pretransplant HBc Ig G seropositivity(OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell nonHodgkin's lymphoma(OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation. CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBc Ig G seropositivity and a diagnosis of T-cell non-Hodgkin's lymphoma should be considered as independent predictor factors of CMV reactivation.
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.
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 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.
文摘In order to compare the effect between haploidentical(HID) stem cell transplantation(HSCT) and matched sibling donor(MSD)stem cell transplantation for high-risk acute myeloid leukemia(AML) in first complete remission status(CR1), we retrospectively studied 170 cases who received stem cell transplantation from Jan 2008 to Jul 2015 in Peking University People's Hospital. We divided all cases into MSD group(43 cases) and HID(127 cases) group. Patients in HID and MSD group displayed similar baseline characteristics except for age distribution. There were no statistic differences for overall survival(OS), cumulative incidence of relapse, leukemia free survival(LFS), transplantation related mortality(TRM) between HID and MSD group. The 3-year OS, LFS for all patients was 63.9% and 59.7% respectively. Multivariate analysis showed that grade III-IV acute graft versus host disease(aGVHD) was an independent risk factor for treatment related mortality(HR=8.134, 95% CI:3.210–20.611, P<0.001), monosomy/complex chromosomal karyotype and white blood cell count more than 50×109 L-1 were two independent factors for relapse(HR=1.533, 95% CI: 1.040–2.260, P=0.031)(HR=1.004, 95% CI: 1.001–1.008, P=0.015).Grade III-IV aGVHD was an independent factor for mortality(HR=3.184, 95% CI: 1.718–5.902, P<0.001). These results demonstrated some risk factors for high-risk AML leukemia transplantation and indicated for AML patients in CR1 status, haplo stem cell transplantation could have the same therapeutic effect as MSD transplantation.
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.
基金supported by National Natural Science Foundation of China (81400143, 81530046, 81621001)National Key Research and Development Plan (2017YFA0104500)
文摘To compare the efficacy of HLA6/6-matched haploidentical hematopoietic stem cell transplant(haplo-HSCT) with that of HLA3/6-matched HSCT in T-cell-replete transplants, we recruited 27 consecutive recipients from multiple centers who received HLA6/6-matched haplo-HSCT from a parent or child donor between February 2010 and May 2016. A matched-pair analysis was designed. For each recipient from the study cohort, two recipients were randomly selected from the control cohort and matched(according to patient age, patient sex, disease type, disease status, donor age, donor sex, and recipient-donor relationship). No significant differences were found in hematopoietic recovery. The incidence of grade II–IV and III–IV acute graft versus host disease was similar(18.5% vs. 31.5%, P=0.216; 11.1% vs. 9.3%, P=0.792) in the HLA6/6 and HLA3/6 groups, respectively. The3-year cumulative incidence of relapse was 14.8% and 17.0%(P=0.800). The 3-year cumulative incidence of nonrelapse mortality was 12.1% and 17.6%(P=0.751). The estimated 3-year disease-free survival was 73.1% and 65.5%(P=0.489). The estimated 3-year overall survival was 74.7% and 74.0%(P=0.946). The data suggested the efficacy and safety of the HLA6/6-and the HLA3/6-matched haplo-HSCT between parents and children are comparable. That HLA-mismatch disparity is not correlated with T-cell-replete haplo-HSCT outcome was substantiated.