Background Relapse happens frequently after allogeneic hematopoietic cell transplantation （alIo-HCT） in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia （Ph^＋ ALL）. Detection of the...Background Relapse happens frequently after allogeneic hematopoietic cell transplantation （alIo-HCT） in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia （Ph^＋ ALL）. Detection of the minimal residual disease （MRD） before and after alIo-HCT is associated with higher relapse rate. Early administration of imatinib after alIo-HCT may prevent recurrent Ph^＋ ALL. The aim of this study was to evaluate the safety and efficacy of imatinib in preventing hematological relapse when imatinib was administrated in the first 90 days after alIo-HCT. Methods Patients with Ph^＋ ALL that underwent alIo-HCT were enrolled in a prospective study. A TaqMan-based real-time quantitative polymerase chain reaction （RQ-PCR） technique was used to detect the MRD （bcr-abl transcript levels）. Imatinib therapy was initiated prior to 90 days after alIo-HCT if the patient＇s absolute neutrophil count （ANC） was above 1.0×10^9/L （without granulocyte colony-stimulating factor （G-CSF） administration） and the platelet count was greater than 50.0×10^9/L, or if the bcr-abl transcript levels were elevated in two consecutive tests, or if the bcr-abl transcript levels were 〉10.2 after the initial engraftment. The initial daily dose of imatinib was 400 mg/d for adults and 260 mg/m^2 for children （younger than 17 years）. Imatinib was administered for at least I month and the bcr-abl TaqMan results were negative for 3 consecutive tests, or complete molecular remission （CR^mol） was sustained for at least 3 months. Results From May 2005 to October 2008, 29 patients were enrolled in this study, of whom, 19 patients were male and 10 were female. The median age of the enrolled patients was 33 years （range 6-50 years）. Imatinib therapy was started at a median time of 60 days （range 20-122 days） post HCT （only one patient started Imatinib therapy at 122nd day after HCT）. Twenty-five adult patients could tolerate a dose of 300-400 mg/d of imatinib, and three children tolerated 展开更多
Background The definite pathogenesis of hemorrhagic cystitis （HC） after allogenic hematopoietic stem cell transplantation （allo-HSCT） has not been well elucidated. The role of cytomegalovirus （CMV） reactivation ...Background The definite pathogenesis of hemorrhagic cystitis （HC） after allogenic hematopoietic stem cell transplantation （allo-HSCT） has not been well elucidated. The role of cytomegalovirus （CMV） reactivation and graft-versus-host disease （GVHD） in the development of HC remains obscure. This study determined the incidence and risk factors for HC after alIo-HSCT and analyzed its association with CMV reactivation and GVHD. Methods We retrospectively studied 250 patients at high risk for CMV disease who underwent alIo-HSCT all based on busulfan/cyclophosphamide （BU/CY） myloablative regimens. The incidence, etiology, risk factors and clinical management of HC were investigated. Results HC developed within 180 days of transplant in 72 patients, with an overall incidence of 28.8% and an incidence of 12.6% in patients with HLA-matched related donors （MRD）, 34.38% in those with HLA-matched unrelated donors （MUD）, 49.45% in those with mismatched related donors （MMRD）. CMV-viremia significantly increased the incidence of later onset HC （LOHC）; however, only 9 out of 15 patients with CMV viruria actually developed LOHC. Multiple regression analysis identified grade II-IV acute GVHD （RR=2.75; 95% CI 1.63-4.66; P〈0.01） and grafts from MUD or MMRD （RR=2.60; 95% CI 1.52-5.20; P〈0.01） as independent risk factors for HC. Event sequence analysis indicated a majority of HC episodes began around GVHD initiation. Conclusions CMV-viremia is a high risk factor for LOHC. Our data also showed a correlation between acute GVHD and HC, which suggested that alloimmunity may be involved in the pathogenesis of HC.展开更多
Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complic...Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complications （NC） are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases （IIDDs） of the central nervous system （CNS） in patients following alIo-HSCT. Methods A nested case-control study was conducted in a large cohort of 1365 patients, who underwent alIo-HSCT at the Institute of Hematology and Peking University People＇s Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0. Results The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients （97.2%） suffered IIDDs after transplantation, 16 patients （44.4%） between day 0 to day 100 post-transplantation, 10 patients （27.8%） between day 100 to 1 year post-transplantation, and 9 patients （25.0%） 1 year post-transplantation. Multivariate regression analysis identified donor type （P=0.031）, infection （P=0.009）, and acute lymphatic leukemia （P=0.017） as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation （95% CI： 223-805）. Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not （26.6% vs. 73.5%, P 〈0.001）. Of the 36 patients experiencing IIDDs, 58.3% （n=21） died. The causes of death were graft-versus-host disease （GVHD） （n=4）, underlying disease relapse （n=3）, infections （n=12）, and other causes （n=2）. Conclusions IIDDs is an uncommon but serious complication of alIo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, an展开更多
Background Hematopoietic growth factor （HGF） is indispensable to hematopoiesis in the body. The proliferation and differentiation of hematopoietic cells must rely on the existence and stimulation of HGF. This study ...Background Hematopoietic growth factor （HGF） is indispensable to hematopoiesis in the body. The proliferation and differentiation of hematopoietic cells must rely on the existence and stimulation of HGF. This study investigated the effect of catechin, an active component extracted from Spatholobus suberectus Dunn （SSD）, on bioactivity of granulocyte-macrophage colony-stimulating activity （GM-CSA）, burst-promoting activity （BPA） and megakaryocyte colony-stimulating activity （MK-CSA） in spleen condition medium （SPCM） of mice to clarify the hematopoietic mechanism of catechin and SSD. Methods Spleen cells of mice were separated and spleen condition medium （SPCM） was prepared from spleen cell culture. Bone marrow cells of mice were separated and cultured in a culture system including 10% （v/v） SPCM （induced by catechin in vivo or ex vivo） for 6 days. Granulocyte-macrophage colony forming units （CFU-GM）, erythrocyte burst-colony-forming units （BFU-E） and megakaryocyte colony-forming units （CFU-Meg） formation were employed to assay the effects of different treatment on the bioactivity of GM-CSA, BPA and MK-CSA in SPCM. Results SPCM induced by 100 mg/L catechin ex vivo could promote the growth of CFU-GM, BFU-E and CFU-Meg, which indicated that catechin could stimulate the production of GM-CSA, BPA and MK-CSA in SPCM. SPCM prepared at the fourth day of spleen cell culture showed the best stimulating activity. The bioactivity of GM-CSA, BPA and MK-CSA in the SPCM prepared after intraperitoneally injecting catechin into mice was also increased. The number of CFU-GM, BFU-E and CFU-Meg gradually increased as the dose of catechin increased and the time of administration prolonged. CFU-GM, BFU-E and CFU-Meg of the high-dose catechin group were significantly higher than those of the control group （P〈0.01） and reached the maximum at the seventh day after administration. Conclusions This study suggests that catechin extracted from the active acetic ether part of Spatholobus su展开更多
Background The pathophysiology of late-onset hemorrhagic cystitis （LOHC） is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic he...Background The pathophysiology of late-onset hemorrhagic cystitis （LOHC） is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A retrospective study was performed on the medical records of 11 patients with immune-related LOHC post allogeneic HSCT. The clinical characteristics, therapy, and outcomes of these patients were analyzed. Results The median time of onset was 42 days after HSCT （range 16-150 days） and the median duration of HC was 43 days （range 29-47 days）. All patients presented with prolonged HC for more than 35 days. Nine patients with evidence of cytomegalovirus （CMV） reactivation did not respond to anti-viral therapy even with CMV clearance in the urine post-therapy. Eleven patients with refractory HC received a low dose of corticosteroids and all patients went into complete remission. Conclusion Our data suggest that alloimmune injury is involved in the pathogenesis of HC in at least some patients and that specific therapy might improve the clinical outcome of hemorrhagic cystitis.展开更多
Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explo...Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made. Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis （GconC） and their related clinical issues. Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa （12 of 32） and deep ulcers （2 of 7） were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively. Conclusions Following allo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.展开更多
Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantat...Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day -10 and cytarabine （2 g/ms） was given on day -9, busulfan was administered orally in four divided doses daily for 3 days （days -8 to -6）. The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%; 95% Cl. 8.4%-32.3%）. Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estima展开更多
Objective： Peripheral T-cell lymphomas （PTCLs） confer dismal prognosis and no consensus has been established on the role of allogeneic hematopoietic stem cell transplantation （allo-HSCT） due to its rarity and het...Objective： Peripheral T-cell lymphomas （PTCLs） confer dismal prognosis and no consensus has been established on the role of allogeneic hematopoietic stem cell transplantation （allo-HSCT） due to its rarity and heterogeneity. The purpose was to review key points ofallo-HSCT for PTCLs, including indication, times of transplantation, conditioning regimen, graft versus host disease prophylaxis, and treatment of relapse.Data Sources： A comprehensive search in PubMed and Cochrane up to February 28, 2018, with the keywords ＂Peripheral＂, ＂T＂, ＂Lymphoma＂, and ＂Transplantation＂ was done. Study Selection： Relevant articles including HSCT for PTCLs were carefully reviewed. Results： Promising data have been reported from advances in transplant technology and more and more PTCLs patients with poor prognosis could benefit from allo-HSCT. Conclusion： Allo-HSCT is a useful choice for patients with refractory/relapsed PTCLs or high-risk new diagnosed PTCLs.展开更多
Background Chronic graft-versus-host disease （GVHD）,the commonest long-term complication after allogeneic hematopoietic stem cell transplantation （HSCT）,has a negative impact on patients＇ health related quality o...Background Chronic graft-versus-host disease （GVHD）,the commonest long-term complication after allogeneic hematopoietic stem cell transplantation （HSCT）,has a negative impact on patients＇ health related quality of life （HRQoL）.This study was designed to investigate the HRQoL in patients with chronic GVHD in China.Methods Two hundred and sixty-four patients with chronic GVHD who were ＞24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective study.HRQoL was evaluated using an SF-36 questionnaire.Multivariate analysis was used to identify the factors that affect HRQoL in patients with chronic GVHD.Results HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe category.In the moderate chronic GVHD category,markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these factors.According to multivariate analysis,chronic GVHD severity had the greatest significant negative impact on patients＇ HRQoL; whereas being female was associated with a negative impact on psychological health.Conclusion Chronic GVHD severity strongly correlates with negative impacts on patients＇ HRQoL.展开更多
Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-...Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A panel of 29 selected sequence polymorphism （SP） markers was screened by real-time polymerase chain reaction （RT-PCR） to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow （BM） samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood （PB） samples of 14 patients at relapse were compared. Results Twenty-one patients experienced leukemia relapse at a median of 135 days （range, 30-720 days） after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% （19/21） of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days （range, 0-120 days）, with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse （P=-0.001）. Conclusions This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recom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
Background The occurrence of bronchiolitis obliterans syndrome （BOS） after allogeneic hematopoietic stem cell transplantation （alIo-HSCT） is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposu...Background The occurrence of bronchiolitis obliterans syndrome （BOS） after allogeneic hematopoietic stem cell transplantation （alIo-HSCT） is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after alIo-HSCT. Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of alIo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent alIo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia. Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was （32.7±2.4） years, and the mean time to presentation was （474±350） days post-HSCT. A pre-HSCT cyclophosphamide dose of 〉3.2 g/m2 （OR=8.74, P=0.025）, chronic graft-versus-host disease （moderate to severe） （OR=12.02, P=0.000）, and conditioning regimens without antithymocyte globulin （OR=2.79, P=0.031） were independently associated with BOS. Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after alIo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.展开更多
Background:Bendamustine was approved in China on May 26th,2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma(NHL).The current study was the registration trial...Background:Bendamustine was approved in China on May 26th,2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma(NHL).The current study was the registration trial and the first reported evaluation of the efficacy,safety,and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.Methods:This was a prospective,multicenter,open-label,single-arm,phase 3 study(NCT01596621;C18083/3076)with a 2-year follow-up period.Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles(and up to eight cycles).The primary endpoint was the overall response rate(ORR);and secondary endpoints were duration of response(DoR),progression-free survival(PFS),safety,and pharmacokinetics.Patients were classified according to their best overall response after initiation of therapy.Proportions of patients in each response category(complete response[CR],partial response[PR],stable disease,or progressive disease)were summarized along with a twosided binomial exact 95%confidence intervals(CIs)for the ORR.Results:A total of 102 patients were enrolled from 20 centers between August 6th,2012,and June 18th,2015.At the time of the primary analysis,the ORR was 73%(95%CI:63%–81%)per Independent Review Committee(IRC)including 19%CR and 54%PR.With the follow-up period,the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment;the median PFS was 18.6 months and 15.3 months,respectively.The most common non-hematologic adverse events(AEs)were gastrointestinal toxicity,pyrexia,and rash.Grade 3/4 neutropenia was reported in 76%of patients.Serious AEs were reported in 29 patients and five patients died during the study.Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.Con展开更多
Background:Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect.This multicenter investigatio...Background:Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect.This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM,and compare the main outcomes with matched-related donors (MRDs).Methods:Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017.A matched-pair analysis was designed.For each haplo recipient,the recipients were randomly selected from the MRD group and were matched according to the following criteria:year of the hematopoietic SCT (±2 years),disease status at transplantation,and the length of follow-up.ults:Seventy cases received MRD and 27 received haploidendcal transplantation.The two groups showed no significant ifferences regarding age,gender,cytogenetic risk,and diagnostic stage.The cumulative incidences of non-relapse mortality (NRM) at1 and 3 years based on donor type were 20.5%(95% confidence interval [CI],10.90-30.10%) and 24.2%(95% CI,13.81-34.59%) for the MRD group and 16.80%(95% CI,1.71-31.89%) and 28.70%(95% CI,8.71-48.69%) for the haplo group,respectively.Cumulative incidence of NRM did not differ significantly between the two groups (x2 =0.031,P =0.861).The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8 %(95 % CI,48.24-71.36 %) and 45.4 %(95 % CI,33.44-57.36%),and 65.6%(95% CI,47.18-84.02%) and 26.8%(95% CI,7.59-46.01%) for MRD and haploidentical donor,respectively.Cumulative incidence of PFS did not differ significantly between the two groups (x2 =0.182,P =0.670).In multivariate analyses,no statistically significant differences were observed between haploidentical and MRD for relapse,NRM,PFS,and overall survival.There were no statistically differences on main outcomes after haploidentical and MRD.Conclusion:Haploidentical 展开更多
Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate ...Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017,a total of 128 patients who received auto-HSCT(n=72)or allo-HSCT(n=56)at eight medical centers across China were included in this study.We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease(95%vs.82%,P=0.027),bone marrow involvement(42%vs.15%,P=0.001),chemotherapy-resistant disease(41%vs.8%,P=0.001),and progression disease(32%vs.4%,P<0.001)at transplantation than those receiving auto-HSCT.With a median follow-up of 30(2–143)months,3-year overall survival(OS)and progression-free survival(PFS)in the auto-HSCT group were 70%(48/63)and 59%(42/63),respectively.Three-year OS and PFS for allo-HSCT recipients were 46%(27/54)and 44%(29/54),respectively.There was no difference in relapse rate(34%[17/63]in auto-HSCT vs.29%[15/54]in allo-HSCT,P=0.840).Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63)compared with 27%(14/54)for allo-HSCT recipients(P=0.004).Subanalyses showed that patients with lower prognostic index scores for PTCL(PIT)who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores(3-year OS:85%vs.40%,P=0.003).Patients with complete remission(CR)undergoing auto-HSCT had better survival(3-year OS:88%vs.48%in allo-HSCT,P=0.008).For patients beyond CR,the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group(3-year OS:51%vs.46%,P=0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China.Auto-HSCT seemed to be associated with better survival for patients in good condition(lower PIT score and/or bett展开更多
High-strength Al-Cu-Mg-Ag-Sm alloy was fabricated and subjected to single-stage aging and pre-aging(two-stage aging). Effect of pre-aging on micros tructure and mechanical properties of the alloy was investigated. It ...High-strength Al-Cu-Mg-Ag-Sm alloy was fabricated and subjected to single-stage aging and pre-aging(two-stage aging). Effect of pre-aging on micros tructure and mechanical properties of the alloy was investigated. It is found that the alloy is mainly composed of α-Al, Al_2Cu, Al_2CuMg and AlCu_4Sm. The number of plate-like Ω Al_2Cu precipitates is comparable to that of rod-like S Al_2 CuMg precipitates in the single-stage aged alloy, whereas, in the two-stage aged alloy, it is much higher than that of S precipitates. Q precipitates have a smaller plate thickness and distribute more uniformly in the two-stage aged alloy than in the single-stage aged alloy.Ultimate tensile strength(UTS) and yield strength of the two-stage aged alloy are 12% higher than those of the single-stage aged one, indicating a better aging hardening caused by the two-stage aging. The increased tensile properties mainly come from both stronger precipitation strengthening caused by more Ω precipitates in the twostage aged alloy and stronger solution strengthening from Mg atoms. The fracture surfaces consist of both dimple zones composed of microscale dimples and platform zones composed of nanoscale dimples. The total area of dimple zones for single-stage aged alloy is much higher than that for two-stage aged alloy, which can be attributed to different numbers of Ω precipitates in the two alloys.展开更多
Background The cause of late-onset hemorrhagic cystitis （LOHC） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） remains obscure. In clinical practice, some LOHC patients respond to immunosuppre...Background The cause of late-onset hemorrhagic cystitis （LOHC） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） remains obscure. In clinical practice, some LOHC patients respond to immunosuppression.The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.Methods With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10-14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients＇ response was evaluated. Along with treatment, CD19^＋ B lymphocyte subsets were measured at various study points.Results From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups： anti-virus responders （Group A, n=6）, corticosteroid responders （Group B1, n=16）,corticosteroid and anti-virus nonresponders （Group C, n=3） according to their clinical response. Percentages of CD19^＋CD5^＋ B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1after the first anti-virus phase, percentages of CD19^＋CD5^＋ lymphocytes significantly increased comparing with those at onset （P=0.022）, and then significantly decreased at PR （P=0.003） and CR （P=0.002） with corticosteroid treatment. But significant change was not observed in Groups A and C.Conclusion The immune etiology seems to be involved in the development of LOHC and the proportion of CD19^＋CD5^＋lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC展开更多
Background Analysis of changes in recipient and donor hematopoietic cell origin is extremely useful to monitor the effect of hematopoietic stem cell transplantation （HSCT） and sequential adoptive immunotherapy by do...Background Analysis of changes in recipient and donor hematopoietic cell origin is extremely useful to monitor the effect of hematopoietic stem cell transplantation （HSCT） and sequential adoptive immunotherapy by donor lymphocyte infusions. We developed a sensitive, reliable and rapid real-time PCR method based on sequence polymorphism systems to quantitatively assess the hematopoietic chimerism after HSCT. Methods A panel of 29 selected sequence polymorphism （SP） markers was screened by real-time PCR in 101 HSCT patients with leukemia and other hematological diseases. The chimerism kinetics of bone marrow samples of 8 HSCT patients in remission and relapse situations were followed longitudinally. Results Recipient genotype discrimination was possible in 97.0% （98 of 101） with a mean number of 2.5 （1-7） informative markers per recipient/donor pair. Using serial dilutions of plasmids containing specific SP markers, the linear correlation （r） of 0.99, the slope between -3.2 and -3.7 and the sensitivity of 0.1% were proved reproducible. By this method, it was possible to very accurately detect autologous signals in the range from 0.1% to 30%. The accuracy of the method in the very important range of autologous signals below 5% was extraordinarily high （standard deviation 〈1.85%） which might significantly improve detection accuracy of changes in autologous signals early in the post-transplantation course of follow-up. The main advantage of the real-time PCR method over short tandem repeat PCR chimerism assays is the absence of PCR competition and plateau biases, with demonstrated greater sensitivity and linearity. Finally, we prospectively analyzed bone marrow samples of 8 patients who received allografts and presented the chimerism kinetics of remission and relapse situations that illustrated the sensitivity level and the promising clinical application of this method. Conclusion This SP-based real-time PCR assay provides a rapid, sensitive, and accurate quantitative assessment of mixed chim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%展开更多
文摘Background Relapse happens frequently after allogeneic hematopoietic cell transplantation （alIo-HCT） in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia （Ph^＋ ALL）. Detection of the minimal residual disease （MRD） before and after alIo-HCT is associated with higher relapse rate. Early administration of imatinib after alIo-HCT may prevent recurrent Ph^＋ ALL. The aim of this study was to evaluate the safety and efficacy of imatinib in preventing hematological relapse when imatinib was administrated in the first 90 days after alIo-HCT. Methods Patients with Ph^＋ ALL that underwent alIo-HCT were enrolled in a prospective study. A TaqMan-based real-time quantitative polymerase chain reaction （RQ-PCR） technique was used to detect the MRD （bcr-abl transcript levels）. Imatinib therapy was initiated prior to 90 days after alIo-HCT if the patient＇s absolute neutrophil count （ANC） was above 1.0×10^9/L （without granulocyte colony-stimulating factor （G-CSF） administration） and the platelet count was greater than 50.0×10^9/L, or if the bcr-abl transcript levels were elevated in two consecutive tests, or if the bcr-abl transcript levels were 〉10.2 after the initial engraftment. The initial daily dose of imatinib was 400 mg/d for adults and 260 mg/m^2 for children （younger than 17 years）. Imatinib was administered for at least I month and the bcr-abl TaqMan results were negative for 3 consecutive tests, or complete molecular remission （CR^mol） was sustained for at least 3 months. Results From May 2005 to October 2008, 29 patients were enrolled in this study, of whom, 19 patients were male and 10 were female. The median age of the enrolled patients was 33 years （range 6-50 years）. Imatinib therapy was started at a median time of 60 days （range 20-122 days） post HCT （only one patient started Imatinib therapy at 122nd day after HCT）. Twenty-five adult patients could tolerate a dose of 300-400 mg/d of imatinib, and three children tolerated
基金supported by the grants from the Scientific Research fund for Capital Medicine Development(No. 2006-1010)the Hi-Tech Research and Development Program of China (No.2006AA02Z4A0).
文摘Background The definite pathogenesis of hemorrhagic cystitis （HC） after allogenic hematopoietic stem cell transplantation （allo-HSCT） has not been well elucidated. The role of cytomegalovirus （CMV） reactivation and graft-versus-host disease （GVHD） in the development of HC remains obscure. This study determined the incidence and risk factors for HC after alIo-HSCT and analyzed its association with CMV reactivation and GVHD. Methods We retrospectively studied 250 patients at high risk for CMV disease who underwent alIo-HSCT all based on busulfan/cyclophosphamide （BU/CY） myloablative regimens. The incidence, etiology, risk factors and clinical management of HC were investigated. Results HC developed within 180 days of transplant in 72 patients, with an overall incidence of 28.8% and an incidence of 12.6% in patients with HLA-matched related donors （MRD）, 34.38% in those with HLA-matched unrelated donors （MUD）, 49.45% in those with mismatched related donors （MMRD）. CMV-viremia significantly increased the incidence of later onset HC （LOHC）; however, only 9 out of 15 patients with CMV viruria actually developed LOHC. Multiple regression analysis identified grade II-IV acute GVHD （RR=2.75; 95% CI 1.63-4.66; P〈0.01） and grafts from MUD or MMRD （RR=2.60; 95% CI 1.52-5.20; P〈0.01） as independent risk factors for HC. Event sequence analysis indicated a majority of HC episodes began around GVHD initiation. Conclusions CMV-viremia is a high risk factor for LOHC. Our data also showed a correlation between acute GVHD and HC, which suggested that alloimmunity may be involved in the pathogenesis of HC.
基金This work was supported by grants From the National Natural Science Foundation of China （No. 81070449）, the National Science Foundation of Beijing （No. 7112139）, the National Key Technology Support Program （No. 2012BA138B03）, and the Capital Clinical Characteristic Application Foundation （No. Zl11107058811024）.The authors thank the nursing staff for providing excellent care to the alIo-HSCT recipients.
文摘Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complications （NC） are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases （IIDDs） of the central nervous system （CNS） in patients following alIo-HSCT. Methods A nested case-control study was conducted in a large cohort of 1365 patients, who underwent alIo-HSCT at the Institute of Hematology and Peking University People＇s Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0. Results The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients （97.2%） suffered IIDDs after transplantation, 16 patients （44.4%） between day 0 to day 100 post-transplantation, 10 patients （27.8%） between day 100 to 1 year post-transplantation, and 9 patients （25.0%） 1 year post-transplantation. Multivariate regression analysis identified donor type （P=0.031）, infection （P=0.009）, and acute lymphatic leukemia （P=0.017） as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation （95% CI： 223-805）. Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not （26.6% vs. 73.5%, P 〈0.001）. Of the 36 patients experiencing IIDDs, 58.3% （n=21） died. The causes of death were graft-versus-host disease （GVHD） （n=4）, underlying disease relapse （n=3）, infections （n=12）, and other causes （n=2）. Conclusions IIDDs is an uncommon but serious complication of alIo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, an
基金This work was supported by a Science Foundation of China （No. grant of the National Natural 30070890）.
文摘Background Hematopoietic growth factor （HGF） is indispensable to hematopoiesis in the body. The proliferation and differentiation of hematopoietic cells must rely on the existence and stimulation of HGF. This study investigated the effect of catechin, an active component extracted from Spatholobus suberectus Dunn （SSD）, on bioactivity of granulocyte-macrophage colony-stimulating activity （GM-CSA）, burst-promoting activity （BPA） and megakaryocyte colony-stimulating activity （MK-CSA） in spleen condition medium （SPCM） of mice to clarify the hematopoietic mechanism of catechin and SSD. Methods Spleen cells of mice were separated and spleen condition medium （SPCM） was prepared from spleen cell culture. Bone marrow cells of mice were separated and cultured in a culture system including 10% （v/v） SPCM （induced by catechin in vivo or ex vivo） for 6 days. Granulocyte-macrophage colony forming units （CFU-GM）, erythrocyte burst-colony-forming units （BFU-E） and megakaryocyte colony-forming units （CFU-Meg） formation were employed to assay the effects of different treatment on the bioactivity of GM-CSA, BPA and MK-CSA in SPCM. Results SPCM induced by 100 mg/L catechin ex vivo could promote the growth of CFU-GM, BFU-E and CFU-Meg, which indicated that catechin could stimulate the production of GM-CSA, BPA and MK-CSA in SPCM. SPCM prepared at the fourth day of spleen cell culture showed the best stimulating activity. The bioactivity of GM-CSA, BPA and MK-CSA in the SPCM prepared after intraperitoneally injecting catechin into mice was also increased. The number of CFU-GM, BFU-E and CFU-Meg gradually increased as the dose of catechin increased and the time of administration prolonged. CFU-GM, BFU-E and CFU-Meg of the high-dose catechin group were significantly higher than those of the control group （P〈0.01） and reached the maximum at the seventh day after administration. Conclusions This study suggests that catechin extracted from the active acetic ether part of Spatholobus su
文摘Background The pathophysiology of late-onset hemorrhagic cystitis （LOHC） is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A retrospective study was performed on the medical records of 11 patients with immune-related LOHC post allogeneic HSCT. The clinical characteristics, therapy, and outcomes of these patients were analyzed. Results The median time of onset was 42 days after HSCT （range 16-150 days） and the median duration of HC was 43 days （range 29-47 days）. All patients presented with prolonged HC for more than 35 days. Nine patients with evidence of cytomegalovirus （CMV） reactivation did not respond to anti-viral therapy even with CMV clearance in the urine post-therapy. Eleven patients with refractory HC received a low dose of corticosteroids and all patients went into complete remission. Conclusion Our data suggest that alloimmune injury is involved in the pathogenesis of HC in at least some patients and that specific therapy might improve the clinical outcome of hemorrhagic cystitis.
文摘Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made. Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis （GconC） and their related clinical issues. Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa （12 of 32） and deep ulcers （2 of 7） were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively. Conclusions Following allo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.
文摘Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day -10 and cytarabine （2 g/ms） was given on day -9, busulfan was administered orally in four divided doses daily for 3 days （days -8 to -6）. The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%; 95% Cl. 8.4%-32.3%）. Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estima
文摘Objective： Peripheral T-cell lymphomas （PTCLs） confer dismal prognosis and no consensus has been established on the role of allogeneic hematopoietic stem cell transplantation （allo-HSCT） due to its rarity and heterogeneity. The purpose was to review key points ofallo-HSCT for PTCLs, including indication, times of transplantation, conditioning regimen, graft versus host disease prophylaxis, and treatment of relapse.Data Sources： A comprehensive search in PubMed and Cochrane up to February 28, 2018, with the keywords ＂Peripheral＂, ＂T＂, ＂Lymphoma＂, and ＂Transplantation＂ was done. Study Selection： Relevant articles including HSCT for PTCLs were carefully reviewed. Results： Promising data have been reported from advances in transplant technology and more and more PTCLs patients with poor prognosis could benefit from allo-HSCT. Conclusion： Allo-HSCT is a useful choice for patients with refractory/relapsed PTCLs or high-risk new diagnosed PTCLs.
基金This work was partly supported by the National High Technology Research and Development Program of China （Program 863, No. 2011AA020105） and the National Natural Science Foundation of China （No. 30971292）.Acknowledgment： This manuscript has been edited by Lena R and Ryan L of American Journal Experts.
文摘Background Chronic graft-versus-host disease （GVHD）,the commonest long-term complication after allogeneic hematopoietic stem cell transplantation （HSCT）,has a negative impact on patients＇ health related quality of life （HRQoL）.This study was designed to investigate the HRQoL in patients with chronic GVHD in China.Methods Two hundred and sixty-four patients with chronic GVHD who were ＞24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective study.HRQoL was evaluated using an SF-36 questionnaire.Multivariate analysis was used to identify the factors that affect HRQoL in patients with chronic GVHD.Results HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe category.In the moderate chronic GVHD category,markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these factors.According to multivariate analysis,chronic GVHD severity had the greatest significant negative impact on patients＇ HRQoL; whereas being female was associated with a negative impact on psychological health.Conclusion Chronic GVHD severity strongly correlates with negative impacts on patients＇ HRQoL.
文摘Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation （HSCT）. Methods A panel of 29 selected sequence polymorphism （SP） markers was screened by real-time polymerase chain reaction （RT-PCR） to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow （BM） samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood （PB） samples of 14 patients at relapse were compared. Results Twenty-one patients experienced leukemia relapse at a median of 135 days （range, 30-720 days） after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% （19/21） of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days （range, 0-120 days）, with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse （P=-0.001）. Conclusions This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recom
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.
基金This work was partly supported by grants of the National High Technology Research and Development Program of China （Program 863） （No. 2011AA020105）, the National Natural Science Foundation of China （No. 30971292）, and the Key Program of National Natural Science Foundation of China （No. 81230013）.
文摘Background The occurrence of bronchiolitis obliterans syndrome （BOS） after allogeneic hematopoietic stem cell transplantation （alIo-HSCT） is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after alIo-HSCT. Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of alIo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent alIo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia. Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was （32.7±2.4） years, and the mean time to presentation was （474±350） days post-HSCT. A pre-HSCT cyclophosphamide dose of 〉3.2 g/m2 （OR=8.74, P=0.025）, chronic graft-versus-host disease （moderate to severe） （OR=12.02, P=0.000）, and conditioning regimens without antithymocyte globulin （OR=2.79, P=0.031） were independently associated with BOS. Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after alIo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.
基金by the Teva Branded Pharmaceutical Products R&D Inc.
文摘Background:Bendamustine was approved in China on May 26th,2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma(NHL).The current study was the registration trial and the first reported evaluation of the efficacy,safety,and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.Methods:This was a prospective,multicenter,open-label,single-arm,phase 3 study(NCT01596621;C18083/3076)with a 2-year follow-up period.Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles(and up to eight cycles).The primary endpoint was the overall response rate(ORR);and secondary endpoints were duration of response(DoR),progression-free survival(PFS),safety,and pharmacokinetics.Patients were classified according to their best overall response after initiation of therapy.Proportions of patients in each response category(complete response[CR],partial response[PR],stable disease,or progressive disease)were summarized along with a twosided binomial exact 95%confidence intervals(CIs)for the ORR.Results:A total of 102 patients were enrolled from 20 centers between August 6th,2012,and June 18th,2015.At the time of the primary analysis,the ORR was 73%(95%CI:63%–81%)per Independent Review Committee(IRC)including 19%CR and 54%PR.With the follow-up period,the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment;the median PFS was 18.6 months and 15.3 months,respectively.The most common non-hematologic adverse events(AEs)were gastrointestinal toxicity,pyrexia,and rash.Grade 3/4 neutropenia was reported in 76%of patients.Serious AEs were reported in 29 patients and five patients died during the study.Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.Con
基金grants from Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001)National Natural Science Foundation of China (Nos. 81670167 and 81670166).
文摘Background:Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect.This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM,and compare the main outcomes with matched-related donors (MRDs).Methods:Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017.A matched-pair analysis was designed.For each haplo recipient,the recipients were randomly selected from the MRD group and were matched according to the following criteria:year of the hematopoietic SCT (±2 years),disease status at transplantation,and the length of follow-up.ults:Seventy cases received MRD and 27 received haploidendcal transplantation.The two groups showed no significant ifferences regarding age,gender,cytogenetic risk,and diagnostic stage.The cumulative incidences of non-relapse mortality (NRM) at1 and 3 years based on donor type were 20.5%(95% confidence interval [CI],10.90-30.10%) and 24.2%(95% CI,13.81-34.59%) for the MRD group and 16.80%(95% CI,1.71-31.89%) and 28.70%(95% CI,8.71-48.69%) for the haplo group,respectively.Cumulative incidence of NRM did not differ significantly between the two groups (x2 =0.031,P =0.861).The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8 %(95 % CI,48.24-71.36 %) and 45.4 %(95 % CI,33.44-57.36%),and 65.6%(95% CI,47.18-84.02%) and 26.8%(95% CI,7.59-46.01%) for MRD and haploidentical donor,respectively.Cumulative incidence of PFS did not differ significantly between the two groups (x2 =0.182,P =0.670).In multivariate analyses,no statistically significant differences were observed between haploidentical and MRD for relapse,NRM,PFS,and overall survival.There were no statistically differences on main outcomes after haploidentical and MRD.Conclusion:Haploidentical
文摘Background:There were few studies on real-world data about autologous hematopoietic stem cell transplantation(auto-HSCT)or allogeneic HSCT(allo-HSCT)in peripheral T-cell lymphoma(PTCL).This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017,a total of 128 patients who received auto-HSCT(n=72)or allo-HSCT(n=56)at eight medical centers across China were included in this study.We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease(95%vs.82%,P=0.027),bone marrow involvement(42%vs.15%,P=0.001),chemotherapy-resistant disease(41%vs.8%,P=0.001),and progression disease(32%vs.4%,P<0.001)at transplantation than those receiving auto-HSCT.With a median follow-up of 30(2–143)months,3-year overall survival(OS)and progression-free survival(PFS)in the auto-HSCT group were 70%(48/63)and 59%(42/63),respectively.Three-year OS and PFS for allo-HSCT recipients were 46%(27/54)and 44%(29/54),respectively.There was no difference in relapse rate(34%[17/63]in auto-HSCT vs.29%[15/54]in allo-HSCT,P=0.840).Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63)compared with 27%(14/54)for allo-HSCT recipients(P=0.004).Subanalyses showed that patients with lower prognostic index scores for PTCL(PIT)who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores(3-year OS:85%vs.40%,P=0.003).Patients with complete remission(CR)undergoing auto-HSCT had better survival(3-year OS:88%vs.48%in allo-HSCT,P=0.008).For patients beyond CR,the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group(3-year OS:51%vs.46%,P=0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China.Auto-HSCT seemed to be associated with better survival for patients in good condition(lower PIT score and/or bett
基金financially supported by the National Natural Science Foundation of China (No. 51171108)the Open Research Fund of Science and Technology on High Strength Structural Materials Laboratory, Central South University, China
文摘High-strength Al-Cu-Mg-Ag-Sm alloy was fabricated and subjected to single-stage aging and pre-aging(two-stage aging). Effect of pre-aging on micros tructure and mechanical properties of the alloy was investigated. It is found that the alloy is mainly composed of α-Al, Al_2Cu, Al_2CuMg and AlCu_4Sm. The number of plate-like Ω Al_2Cu precipitates is comparable to that of rod-like S Al_2 CuMg precipitates in the single-stage aged alloy, whereas, in the two-stage aged alloy, it is much higher than that of S precipitates. Q precipitates have a smaller plate thickness and distribute more uniformly in the two-stage aged alloy than in the single-stage aged alloy.Ultimate tensile strength(UTS) and yield strength of the two-stage aged alloy are 12% higher than those of the single-stage aged one, indicating a better aging hardening caused by the two-stage aging. The increased tensile properties mainly come from both stronger precipitation strengthening caused by more Ω precipitates in the twostage aged alloy and stronger solution strengthening from Mg atoms. The fracture surfaces consist of both dimple zones composed of microscale dimples and platform zones composed of nanoscale dimples. The total area of dimple zones for single-stage aged alloy is much higher than that for two-stage aged alloy, which can be attributed to different numbers of Ω precipitates in the two alloys.
文摘Background The cause of late-onset hemorrhagic cystitis （LOHC） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） remains obscure. In clinical practice, some LOHC patients respond to immunosuppression.The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.Methods With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10-14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients＇ response was evaluated. Along with treatment, CD19^＋ B lymphocyte subsets were measured at various study points.Results From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups： anti-virus responders （Group A, n=6）, corticosteroid responders （Group B1, n=16）,corticosteroid and anti-virus nonresponders （Group C, n=3） according to their clinical response. Percentages of CD19^＋CD5^＋ B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1after the first anti-virus phase, percentages of CD19^＋CD5^＋ lymphocytes significantly increased comparing with those at onset （P=0.022）, and then significantly decreased at PR （P=0.003） and CR （P=0.002） with corticosteroid treatment. But significant change was not observed in Groups A and C.Conclusion The immune etiology seems to be involved in the development of LOHC and the proportion of CD19^＋CD5^＋lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC
文摘Background Analysis of changes in recipient and donor hematopoietic cell origin is extremely useful to monitor the effect of hematopoietic stem cell transplantation （HSCT） and sequential adoptive immunotherapy by donor lymphocyte infusions. We developed a sensitive, reliable and rapid real-time PCR method based on sequence polymorphism systems to quantitatively assess the hematopoietic chimerism after HSCT. Methods A panel of 29 selected sequence polymorphism （SP） markers was screened by real-time PCR in 101 HSCT patients with leukemia and other hematological diseases. The chimerism kinetics of bone marrow samples of 8 HSCT patients in remission and relapse situations were followed longitudinally. Results Recipient genotype discrimination was possible in 97.0% （98 of 101） with a mean number of 2.5 （1-7） informative markers per recipient/donor pair. Using serial dilutions of plasmids containing specific SP markers, the linear correlation （r） of 0.99, the slope between -3.2 and -3.7 and the sensitivity of 0.1% were proved reproducible. By this method, it was possible to very accurately detect autologous signals in the range from 0.1% to 30%. The accuracy of the method in the very important range of autologous signals below 5% was extraordinarily high （standard deviation 〈1.85%） which might significantly improve detection accuracy of changes in autologous signals early in the post-transplantation course of follow-up. The main advantage of the real-time PCR method over short tandem repeat PCR chimerism assays is the absence of PCR competition and plateau biases, with demonstrated greater sensitivity and linearity. Finally, we prospectively analyzed bone marrow samples of 8 patients who received allografts and presented the chimerism kinetics of remission and relapse situations that illustrated the sensitivity level and the promising clinical application of this method. Conclusion This SP-based real-time PCR assay provides a rapid, sensitive, and accurate quantitative assessment of mixed chim
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%
