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Objective@#To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) .@*Methods@#The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored.@*Results@#①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ2=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ2=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ2=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ2=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) .@*Conclusions@#HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.
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Objective@#To evaluate the outcomes and prognostic factors of myelodysplasia syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#165 cases of MDS who underwent allo-HSCT from Jan. 2010 to Mar. 2018 were analyzed retrospectively, focusing on the overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) and their related risk factors.@*Results@#Of all the 165 cases, 105 were male and 60 were female. The 3-year OS and DFS rate were 72.5% (95%CI 64.9%-80.1%) and 67.4% (95%CI 59.17%-75.63%) , respectively. The 3-year cumulative incidence of relapse and NRM were 12.11% (95%CI 7.03%-18.65%) and 20.44% (95%CI 14.15%-27.56%) , respectively. HCT-comorbidity index (P=0.042, HR=2.094, 95%CI 1.026-4.274) was identified as independent risk factor for OS by the multivariate analysis. Intensive chemotherapy before HSCT or hypomethylation agents treatment had no effects on OS[ (67.0±7.5) %vs (57.7±10.9) %, χ2=0.025, P=0.874].@*Conclusions@#allo-HSCT is a promising means for MDS, and NRM is the major cause of treatment failure. MDS with refractory anemia with excess blasts and secondary acute myeloid leukemia patients may not benefit from intensive chemotherapy or hypomethylation agents treatment before HSCT.
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Objective@#To assess the efficacy and toxicity of decitabine-based conditioning regimen in patients with myelodysplastic syndrome (MDS) , acute myeloid leukemia secondary to MDS (MDS-AML) or chronic myelomonocytic leukemia (CMML) .@*Methods@#From March 1, 2013 to May 25, 2015, 22 patients who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) with decitabine-based conditioning regimen were analyzed retrospectively.@*Results@#①22 patients, 14 males and 8 females with a median age of 42.5 (24-56) years old, were diagnosed as MDS (n=14) , CMML (n=4) , MDS-AML (n=4) . ②15 patients were treated with the conditioning regimen of decitabine combined with busulfan, cyclophosphamide, fludarabine, and cytarabine, the other 7 cases were treated with decitabine, busulfan, fludarabine, and cytarabine. The dose of decitabine was 20 mg·m-2·d-1 for 5 days.Rabbit anti-human anti-thymocyte globulin (2.5 mg·kg-1·d-1 for 4 days) was involved in conditioning regimen in patients with unrelated donor or haploidentical transplantation. ③Except 1 patient died of infection in 2 months after transplantation, the other patients were engrafted successfully. The median time of granulocyte engraftment was 13 (12-18) days, and the median time of platelet engraftment was 16 (13-81) days. ④The incidence of acute graft versus host disease (aGVHD) was (41.3±10.6) %, and severe aGVHD (grade of III-IV) was (18.4±9.7) %. The incidence of chronic graft versus host disease (cGVHD) was (56.4±11.3) %, and extensive cGVHD was (36.4±12.1) %. ⑤8 patients were suffered with cytomegalovirus (CMV) viremia. Among the 18 patients with definitely infection, 6 occurred during myelosuppression and 12 cases occurred after hematopoietic reconstruction. The 2-year and 3-year non-relapse mortality was (13.9±7.4) % and (24.3±9.5) %, respectively. ⑥The 2-year and 3-year overall survival (OS) was (77.3±8.9) % and (67.9±10.0) %, respectively. The 2-year and 3-year relapse-free survival (RFS) was (72.7±9.5) % and (63.6±10.3) %, respectively.@*Conclusions@#allo-HSCT with decitabine-based conditioning regimen is feasible in the treatment of MDS, MDS-AML or CMML.
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Objective@#To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center.@*Methods@#Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed.@*Results@#A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade Ⅲ-Ⅳ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups.@*Conclusions@#The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.
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Objective To explore the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myelomonocytic leukemia (CMML) patients .Methods The clinical data were retrospectively analyzed for 19 CMML patients undergoing allo-HSCT .Engraftment ,graft versus host disease (GVHD ) , infection , relapse , splenomegaly and survival were observed . And the clinical outcomes of allo-HSCT for CMML were analyzed .Results Hematopoiesis reconstitution was not attained in 2 recipients due to early death post-transplantation .Neutrophil engraftment was obtained in 17 recipients with a median time of 14(11-18) days .Neutrophil engraftment and platelet engraftment were achieved in 15 recipients with a median time of platelet engraftment at 15 (12～70) days .Seven patients developed acute GVHD (grade 1 ,n=5;grade 2～4 ,n=3) while another 8 patients had chronic GVHD (extensive ,n=5) . Ten patients (52 .6 ％ )had palpable splenomegaly (SPM ) before allo-HSCT ,8 patients were diagnosed ultrasonically after transplantation ,all 4 patients without a significant reduction of spleen died while all 4 patients with a significant reduction of spleen survived . After a median follow-up period of 31 (6-68 ) months ,3-year overall survival (OS) ,disease-free survival (DFS) ,cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were (58 .2 ± 12 .5)％ ,(36 .3 ± 14)％ ,(39 .9 ± 19)％ and (37 ± 12 .6)％ respectively .Conclusions As an effective therapy for CMML ,allo-HSCT may improve the survival of CMML patients .Palpable SPM pre-transplantation and no significant reduction post-transplantation are probably poor prognostic factor .
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Objective To explore the effect of iron overload on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patiems with non-hepatitis related severe aplastic anemia (SAA).Methods The clinical data were retrospectively analyzed for 98 patients with non-hepatitis related SAA undergoing allo-HSCT from July 2012 to late July 2018 at a single center.Serum ferritin (SF) was measured within 2 momhs before HSCT.They were divided into iron overload (SF＞800.0 ng/ml,n =49) and control (SF＜800.0 ng/ml,n =49) groups according to SF level.Overall survival (OS),hematopoietic reconstitution and common complications after allo-HSCT were analyzed.Results The median pre-transplantation SF value was 798.7 (52.0-11060.01) ng/ml.Patients with pre-transplantation iron overload had a higher incidence of cytomegaloviremia (P =0.041),delayed recovery of neutrophil/platelet (P =0.001,P =0.005 respectively) and transfusion-dependence in donor-recipient blood group-matched patients (P =0.043) after allo-HSCT.The 3-year OS was (65.1 ± 7.1) ％ in iron overload group and (93.3 ± 3.7) ％ in control group (P =0.001).Multivariate analysis indicated that 3-year OS was independently correlated with pre-transplantation iron overload (P =0.022),blood group of donor & recipient (P =0.015),early bacteremia (P=0.003) and cytomegaloviremia (P =0.003).Conclusions Iron overload is common in patients with non-hepatitis-related SAA before transplantation.Pre-transplantation iron overload has a significant impact on OS,hematopoietic reconstitution and cytomegaloviremia after allo
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Objective@#To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT).@*Methods@#The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation.@*Results@#The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively].@*Conclusion@#The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.
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Objective@#To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA.@*Methods@#HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed.@*Results@#Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ2=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion.@*Conclusion@#DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.
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Objective@#To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of acute myeloid leukemia (AML) patients with FLT3-ITD mutation.@*Methods@#From September 2008 to December 2016, 40 AML patients with FLT3-ITD mutation were enrolled in the study. The therapeutic process, outcomes and prognostic factors were retrospectively analyzed.@*Results@#The median of WBC at initial diagnosis was 35.0 (range 1.7-185.0) ×109/L. The median course number of chemotherapy was 4 (range 2-7). At the time of transplantation, 34 patients were at the first complete remission (CR1) stage, and the other 6 ones were non-remission after chemotherapy. 24 patients received allogeneic transplants from an HLA-matched sibling donor, 7 cases from a HLA-matched unrelated donor, the remaining 9 ones received allograft from a haploidentical donor. The rate of 3-year overall survival (OS) and disease free survival (DFS) in all patients were both 74.3% (95% CI 60.4%-88.2%). The 3-year cumulative incidences of disease relapse and non-relapse mortality were 7.5% (95%CI 1.9%-18.4%) and 18.2% (95% CI 7.9%-32.0%), respectively. More than one course of chemotherapy before achieving CR1 and the occurrence of acute GVHD after transplantation were associated with poor outcome in terms of OS and DFS. The relapse rates were significantly lower in patients receiving transplantation at CR1 stage [0 vs 50.0% (95%CI 77.7%-82.9%) , P<0.001] and achieving CR1 after one course induction therapy [0 vs 16.7% (95%CI 3.9%-37.3%) , P=0.020].@*Conclusions@#Allo-HSCT was an efficient approach for AML patients with FLT3-ITD mutation. Patients obtained better survival, especially for those achieving CR after one course induction therapy and receiving transplantation at CR1 stage.
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Objective@#To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin (ATG) in patients undergoing peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors (MSD) given both the patients and donors were aged over forty years old.@*Methods@#From March 2013 to April 2017, 98 patients with hematologic malignancies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG (Sanofi, 1.5 mg/kg per day for 3 consecutive days) before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed.@*Results@#①Neutrophil engraftment was achieved earlier in ATG group than the control one [13(11-17)d vs 14(12-24)d, P=0.001]. The time to platelet engraftment was similar between the two groups [14(11-43)d vs 15(11-42)d, P=0.071]. ②The cumulative incidence of aGVHD was significantly lower in ATG group [25.6% (95%CI 13.7%-39.3%) vs 49.1% (95%CI 35.2%-61.6%), P=0.018]. The incidences of grade Ⅱ-Ⅳ aGVHD [18.6% (95%CI 8.6%-31.5%) vs 23.6% (95%CI 13.4%-35.6%), P=0.509] and cGVHD [49.6% (95% CI 31.6%-65.3%) vs 56.4% (95% CI 41.4%-69.0%), P=0.221] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [21.1%(95%CI 10.3%-34.5%) vs 31.1% (95%CI 18.8%-44.2%), P=0.429]. ④The cumulative incidences of disease relapse [24.0%(95%CI 11.5%-38.9%) vs 24.0% (95% CI 12.1%-38.2%), P=0.608), non-relapse mortality [10.2% (95% CI 3.1%-22.1%) vs 21.6% (95% CI 9.4%-37.0%), P=0.411] and DFS [65.8% (95%CI 50.3%-81.3%) vs 54.4% (95%CI 37.7%-71.1%), P=0.955] were comparable between the two groups. 2-year overall survival (OS) was significantly better in ATG group than the control one [83.8% (95% CI 71.8%-90.0%) vs 58.0% (95% CI 42.2%-73.9%), P=0.019].@*Conclusion@#The addition of low-dose ATG decreased the incidence of aGVHD and improved OS. The incidences of viral infections and disease relapse remained to be similar between the two groups. These results suggested that elderly patients undergoing MSD-PBSCT may benefit from this low-dose ATG containing GVHD prophylaxis regimen.
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Objective@#To compare eficacy and safety of porcine antihuman lymphocyte immunoglobulin (pALG) and rabbit antithymocyte immunoglobulin (rATG) as a part of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) for severe aplastic anemia (SAA).@*Methods@#The clinical data of 46 SAA patients received AD allo-HSCT from January 2006 to November 2016 were retrospectively analyzed. The cohort of patients were divided into two groups based on rATG or pALG as a part of conditioning regimen to compare implantation rate, transplantation related complications and outcome.@*Results@#In rATG group 30 patients achieved ANC reconstitution, 27 patients achieved PLT reconstitution. In pALG group all 16 patients achieved ANC and PLT reconstitutions. There were no significant differences between the two groups in terms of acute graft-versus-host disease (aGVHD) (P=0.475), Ⅲ-Ⅳ grade aGVHD (P=0.876), chronic GVHD (cGVHD) (P=0.309), extensive cGVHD (P=0.687), graft rejection (GR) (P=0.928), bloodstream infection (P=0.443), invasive fungal disease (P=0.829), cytomegalovirus viremia (P=0.095) respectively. Prospective 5-year overall survival (OS) in rATG and pALG groups were (75.1±8.2)% and (53.6±13.3)% with median follow-up of 14(2-102) and 23(4-63) months, respectively (P=0.190).@*Conclusion@#As a part of conditioning regimen, pALG could achieve similar efficacy as rATG, without increasing the incidences of transplantation complications such as GVHD, GR and infection, in the setting of AD allo-HSCT for SAA patients.
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Objective To explore the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory acute myeloid leukemia (AML) patients in nonremission (NR) status and its related risk factors.Methods Thirty-nine relapsed/refractory AML patients in NR status who received allo-HSCT between Jan.2006 and Dec.2016 were retrospectively analyzed.Major end points of study included overall survival (OS),disease free survival (DFS),and relapse rate.Results All patients achieved hematopoietic reconstitution.Median time to neutrophil and platelet engraftment was 13 (11 20) and 16 (10-58) days,respectively.Acute graft-versus-host disease (aGVHD) occurred in 25 (64.1％) patients,and 11 (31.4％) patients developed chronic GVHD.During a median follow-up period of 9.1 (1.6-93.8) months,11 (28.9％) cases survived,10(26.3％) survived without leukemia,and 21 (53.8％) relapsed.The estimated 2 year OS and DFS were 30.0％ ± 8.0％ and 26.7％ ± 7.7％,and cumulative incidence of relapse and transplantation related mortality at 2 years was 56.63％ (95％ CI 37.84％-71.71％),19.7％ (95％ CI 8.3％-34.5％),respectively.The multivariate analysis revealed that the number of bone marrow blasts≥25％ or any level of blasts in peripheral blood was significantly associated with worse OS (HR =11.91,P=0.003),DFS (HR =10.75,P =0.002) and higher rate of relapse (70.83％ versus 20.22％,P =0.002).In addition,the development of grade Ⅱ-Ⅳ aGVHD also predicted an inferior OS (HR =3.18,P =0.039).Conclusion Salvage therapy with allo-HSCT can induce long-term survival in part refractory/relapsed AML patients.Decrease in the pre-transplant disease burden is the key to reduce relapse and improve survival.
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Objective@#To evaluate the outcomes and prognostic factors of patients with refractory and relapsed acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#The overall survival (OS) , disease free survival (DFS) , acute and chronic graft-versus-host disease (GVHD) , relapse rate (RR) , transplantation related mortality (TRM) and their related risk factors were analyzed retrospectively.@*Results@#All the patients (median age 35 years, range 6 to 58) received myeloablative conditioning regimens. All patients had successful engraftment, and the median time of neutrophils engraftment was 14 days (range 9 to 25) . Of the patients who survived more than 100 days, the accumulative incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD (cGVHD) were 27.3% (95%CI 18.9%-36.3%) , 33.9% (95%CI 24.6%-43.5%) , respectively. Meanwhile, the accumulative incidence of extensive cGVHD was 9.3% (95%CI 4.5%-16.1%) . The 3-year OS, DFS, RR, and TRM was 45.0% (95%CI 34.6%-55.4%) , 45.0% (95%CI 34.8%-55.2%) , 36.6% (95%CI 26.9%-46.4%) and 19.7% (95%CI 12.4%-28.3%) respectively. Multivariate analysis revealed four independent risk factors: non remission status before transplantation[P=0.009, HR=2.21 (95%CI 1.22-4.04) ], WBC at diagnosis>50×109/L[P=0.024, HR=2.11 (95%CI 1.11-4.02) ], donor age>35 years [P=0.031, HR=1.96 (95%CI 1.06-3.60) ]and without cGVHD[P=0.008, HR=0.38 (95%CI 0.18-0.78) ]. According to the risk factors before transplantation (non remission status, WBC at diagnosis>50×109/L, donor age>35 years) , we then defined three subgroups with striking different OS at 3 years: no adverse factor (75.0%) ; one adverse factor (46.9%) ; two or three adverse factors (15.4%) (χ2=26.873, P<0.001) .@*Conclusion@#Allo-HSCT is a promising and safe choice for patients with refractory and relapsed AML and relapse is the major cause of the transplantation failure. Disease status before transplantation, donor age, WBC at diagnosis and cGVHD are confirmed as prognostic factors for these patients who received allo-HSCT.
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Objective@#To respectively analyze the impact of conditioning regimens with a dose-decreased cyclophosphamide (Cy) on the outcome in fully matched sibling donor (MSD) peripheral blood stem cell transplantation (PBSCT) for severe aplastic anemia (SAA) .@*Methods@#Two conditioning regimens with different doses of Cy (150 mg/kg or 120 mg/kg) in combination with fludarabine (Flu) and antithymocyte globulin (ATG) for MSD-PBSCT were investigated in 51 patients with acquired SAA.@*Results@#Overall survival and failure-free survival in patients received 150 mg/kg of Cy (Cy150 cohort) or 120 mg/kg (Cy120 cohort) were 93.5% vs 90.0% (χ2=0.170, P=0.680) and 90.3% vs 85.0% (χ2=0.285, P= 0.594) respectively. However, either acute or chronic graft-versus-host disease risks were higher in Cy120 cohort than in Cy150 cohort (HR=3.89, 95% CI 1.21-12.53, P=0.023; HR=4.48, 95% CI 1.40-14.32, P= 0.011, respectively) . No difference was found for opportunistic infections or graft failure between two cohorts.@*Conclusion@#Cy at a dose of 150 mg/kg, in combination with Flu and ATG, was more effective than that of 120 mg/kg Cy to produce improved clinical outcome in the setting of acquired SAA patients after MSD-PBSCT.
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<p><b>OBJECTIVE</b>To compare the outcomes of adult patients with acute lymphoblastic leukemia (ALL) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>From Jan 2007 to Dec 2010, 106 adult ALL patients were retrospectively divided into two groups, 50 in auto-HSCT group and 56 in allo-HSCT group. Auto-HSCT group included 21 patients with high-risk, 46 patients in CR1 and 4 cases in CR2. All the 50 patients had negative minimal residual disease (MRD) prior to HSCT. Allo-HSCT group included 44 patients with high risk, 51 patients in CR1 and 5 cases in CR2, 15 patients with positive MRD before allo-HSCT. response, regulatory T cells (Treg), cytokines levels and treatment-related adverse effects were observed.</p><p><b>RESULTS</b>Of the total 106 patients, 29 patients relapsed at a medium follow-up of 22.9(0.8-63.3) months. The 3-year cumulative relapse rate (RR) was (29.9±8.0) % in auto-HSCT group and (32.7±6.8) % in allo-HSCT group. There were no significant differences in RR and overall survival (OS) between auto-HSCT and allo-HSCT groups, even of stratified risk groups. In standard risk group, 3-year OS was (77.1±13.2) % in auto-HSCT group and (90.9±8.7) % in allo-HSCT group (P=0.739). In high-risk group, 3-year OS was (68.7±10.8) % after auto-HSCT and (45.2±8.5) % after allo-HSCT (P=0.094).</p><p><b>CONCLUSION</b>Due to acceptable RR and OS, adult ALL patients with no MRD before HSCT showed favorable survival. Auto-HSCT may be a considerable choice for adult ALL patients with negative MRD when lacking of donors for allo-HSCT.</p>
Subject(s)
Adult , Humans , Allografts , Hematopoietic Stem Cell Transplantation , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Recurrence , Retrospective Studies , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To better understand predictive factors and role of autologous hematopoietic stem cell transplantation (auto-HSCT)in the post-remission therapy for adult Ph-negative B-cell acute lymphoblastic leukemia (B-ALL)patients.</p><p><b>METHODS</b>Outcomes of 86 adult patients with B-ALL who received auto-HSCT in our center from January 1996 to February 2014 were retrospectively analyzed.</p><p><b>RESULTS</b>Overall survival (OS)and disease free survival (DFS)at 5 years for the cohort were (63.8 ± 5.6)% and (60.9 ± 5.6)%, respectively. The cumulative non-relapse mortality (NRM)and relapse at 5 years were (4.70 ± 0.05)% and (34.40 ± 0.31)%. For DFS, age ≥ 35 years, high lactate dehydrogenase at diagnosis, high initial WBC count, blast cell proportion ≥ 5% on 15th day of the first induction therapy, complete remession (CR)1 to HSCT interval >6 months and CD34⁺ cells in graft ≥ 3.8 × 10⁶/kg were the poor prognostic factors. CR1 to HSCT interval >6 months was the independently undesirable factors in COX regression model. For 34 patients who had results of minimal residual disease (MRD), positive pretransplantation MRD (MRD≥0.01%), positive post-induction MRD or MRD positive again during the chemotherapy indicated poor prognosis, and the last one was the independent adverse prognostic factor.</p><p><b>CONCLUSION</b>Auto-HSCT combined with post-transplantation maintenance chemotherapy could be an optional approach for adult B-ALL patients. MRD plays a significant role in the treatment choice for adult Ph-negative B-ALL patients.</p>
Subject(s)
Adult , Humans , Acute Disease , Disease-Free Survival , Hematopoietic Stem Cell Transplantation , Maintenance Chemotherapy , Neoplasm, Residual , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Therapeutics , Recurrence , Retrospective Studies , Survival RateABSTRACT
<p><b>OBJECTIVE</b>To evaluate melphalan instead of cyclophosphamide in modified busulfancyclophosphamide regimen as a new myeloablative conditioning regimen for the treatment of myeloid malignancies patients receiving allogeneic hematopoietic stem cell transplantation （HSCT）.</p><p><b>METHODS</b>The clinic data of 94 myeloid malignancies patients undergoing allogeneic HSCT were analyzed, of which 48 patients received Bu+Cy+Flu+Ara-C, 46 cases Bu+Mel+Flu+Ara-C regimens. Rregimen-related toxicity, engraftment, graft- versus-host disease（GVHD）, infection condition, non- relapse mortality, and overall survival were compared between the two groups.</p><p><b>RESULTS</b>All patients achieved neutrophil engraftment. The incidence of grade Ⅲ-Ⅳ oral mucositis and diarrhea in BMFA group was higher than in BCFA group（P<0.05）. The incidence of acute GVHD in BMFA group was also higher than in BCFA group but without statistically significant difference（36.5% over 56.5%, P=0.100）. With a median follow up of 42 months, the incidence of no relapse mortality in BCFA group was 12.5% and 19.6% in BMFA group（P=0.400）. The relapse rate in BMFA group（4.3%）was significantly lower than in BCFA group （25.0%, P=0.009）. The overall survival rates were（71.8±6.7）% and（76.1±6.3）%（P=0.852）, and diseasefree survival rates were（67.8±8.9）% and（76.1±6.3）%（P=0.567）were comparable between BCFA group and BMFA group.</p><p><b>CONCLUSION</b>Melphalan instead of cyclophosphamide as a new myeloablative conditioning regimen had lower relapse and satisfied disease-free survival rates, but the risk of regimenrelated toxicity and GVHD should be taken into consideration.</p>
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Therapeutic Uses , Disease-Free Survival , Graft vs Host Disease , Hematologic Neoplasms , Therapeutics , Hematopoietic Stem Cell Transplantation , Melphalan , Therapeutic Uses , Myeloproliferative Disorders , Therapeutics , Neoplasm Recurrence, Local , Remission Induction , Survival Rate , Transplantation Conditioning , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) in the treatment of severe aplastic anemia (SAA).</p><p><b>METHODS</b>Retrospective analysis of the clinical data of 19 SAA patients received AD allo-HSCT from May 2003 to December 2012. Of them, 12 received haploidentical HSCT (haplo-HSCT), 7 received unrelated donor transplantation. The conditioning regimen was CY+ATG+Flu±Ara-C±Bu/Mel, the GVHD preventing regimen was MMF+MTX+CSA/FK506; the median reinfusion quantity of CD34+ was 3.10(2.11-4.38)×10⁶/kg in allo-BMT and 4.90(2.08-6.88)×10⁶/kg in allo-PBSCT.</p><p><b>RESULTS</b>Hematopoiesis reconstitution was achieved in all 19 patients. Twelve patients developed acute graft-versus-host disease (aGVHD), and 7 developed chronic GVHD (cGVHD). Graft rejection (GR) was occurred in one patient. The median follow-up time was 13(3-115) months. Thirteen patients survived, and the prospective 5-year overall survival rate is (67.5±11.0)%.</p><p><b>CONCLUSION</b>AD allo-HSCT can be used as an alternative therapy for SAA patients without HLA matched sibling donor.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Young Adult , Anemia, Aplastic , Therapeutics , Hematopoietic Stem Cell Transplantation , Retrospective Studies , Tissue Donors , Transplantation, Homologous , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To explore the impact of interleukin-18 (IL-18) single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Single- nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and infections, transplant related mortality (TRM), and disease free survival (DFS) were analyzed.</p><p><b>RESULTS</b>In comparison with -137 G/C+C/C donor genotype, patients with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11-23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype also had higher incidence (33.3%) of extensive chronic GVHD than those with C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM, and DFS between different genotypes.</p><p><b>CONCLUSION</b>IL-18 -137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo-HSCT.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Disease-Free Survival , Genotype , Graft vs Host Disease , Epidemiology , Hematologic Neoplasms , Genetics , Therapeutics , Hematopoietic Stem Cell Transplantation , Methods , Incidence , Interleukin-18 , Genetics , Polymorphism, Single Nucleotide , Siblings , Tissue Donors , Transplantation, HomologousABSTRACT
Objective To explore the impact of IL-10 gene polymorphisms on the outcome in HLA matched sibling hematopoietic stem cell transplantation (HSCT).Methods PCR-sequencespecific primer (PCR-SSP) assay was used to analyze the SNP of IL-10 in 77 recipient and donor pairs:-1082 A/G,-819 T/C,-592 C/A.Results IL-10 ATA/ATA (1082,-819,-592) genotype in recipients significantly decreased the incidence of grade Ⅱ-Ⅳ acute graft vursus-host disease (aGVHD) (6.1％ vs.25.0 ％,P＜0.05),reduced 5-year transplant-related mortality (TRM) (10.7 ％± 5.9％ vs.29.7％ ± 5.2％,P＜0.05) and increased disease free survival (DFS) (81.8％ ± 6.7％ vs.56.8％ ± 7.5％,P＜0.05).With regard to the donor genotype,the incidence of grade Ⅱ-Ⅳ aGVHD,extensive chronic GVHD,5-year TRM and DFS had no signicant difference between IL-10 ATA/ATA and non ATA/ATA subgroup.Multivariable analysis also revealed that IL-10 non-ATA/ATA genotype in recipients and high-risk status of disease were two independent risk factors for DFS (HR =2.911,P =0.029; HR =2.686,P =0.027).Conclusion In HLA-matched sibling HSCT,the presence of recipient IL-10 ATA/ATA significantly decreased the incidence of grade Ⅱ-Ⅳ aGVHD and TRM,and increased DFS.