Maintenance therapy following allogeneic hematopoietic stem cell transplantation in myeloid neoplasms / 白血病·淋巴瘤

The acute myeloid leukemia and myelodysplastic syndromes are common myeloid neoplasms for which allogeneic hematopoietic stem cell transplantation is one of the main curative therapies. In high-risk patients, the relapse rate can be more than 40%, and patients with post-transplantation relapses have a very poor prognosis, so preventing relapse after transplantation is crucial. The maintenance therapy is a group of interventions to prevent relapse when morphological, molecular biological and cytogenetic results are constantly negative after transplantation. Currently, the commonly used maintenance therapy is the application of demethylating drugs, targeted drugs, etc., but their necessity, medicine plan, adverse effects, multi-drug combinations, and other aspects need to be studied urgently. This article will systematically describe the progress of post-transplantation maintenance therapy for high-risk myeloid neoplasms based on drug classification.

Clinical application progress of novel targeted drug gilteritinib in treatment of acute myeloid leukemia with FLT3 mutation / 白血病·淋巴瘤

Acute myeloid leukemia (AML) patients with FLT3 mutation have a high risk of recurrence and poor prognosis. The first generation of drugs targeting FLT3 represented by sorafenib show poor selectivity and efficacy in the treatment of AML, whereas the new second-generation FLT3 inhibitors represented by gilteritinib have a stronger inhibitory effect on FLT3, higher specificity and lower off-target toxicity, which greatly improves the outcomes of AML patients with FLT3 mutation. This article reviews the action mechanism and the clinical progress of gilteritinib.

Outcomes of 138 myelodysplastic syndrome patients with HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

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.

Outcomes and prognostic factors of myelodysplastic syndrome patients with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

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.

Decitabine-based conditioning regimen is feasible and effective in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia / 中华血液学杂志

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.

HLA-10/10 matched unrelated donor versus sibling donor hematopoietic stem cell transplantation for adult acute myeloid leukemia / 中华血液学杂志

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.

Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia / 中华器官移植杂志

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 .

Effect of pre-transplantation iron overload on the outcomes of allogeneic hematopoietic stem cell transplantation patients with non-hepatitis-related severe aplastic anemia / 中华器官移植杂志

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

Prognostic significance of early phase donor chimerism after allogeneic peripheral blood stem cell transplantation / 中华血液学杂志

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.

Effects of preexisting donor-specific HLA antibodies for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

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.

Outcome of acute myeloid leukemia with FLT3-ITD mutation treated by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

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.

Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation / 中华血液学杂志

Objective@#To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. @*Method@#The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR2) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR2 rate was analyzed. @*Results@#68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR2. All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR2 compared with non-KIT D816 group (23.1% vs 57.1%, χ2=7.559, P=0.006), and patients with longer CR1 duration achieved significantly higher CR2 than those with CR1 duration less than 12 months (74.1% vs 31.9%, χ2=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR1 duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. @*Conclusion@#KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.

Application of low-dose ATG for GVHD prophylaxis in patients undergoing PBSCT aged over forty years old / 中华血液学杂志

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.

Clinical efficacy and safety of porcine antihuman lymphocyte immunoglobulin in alternative donor allogeneic hematopoietic cell transplantation for severe aplastic anemia / 中华血液学杂志

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.

Outcome of allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute myeloid leukemia in NR status / 中华器官移植杂志

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.

Improved outcome by optimized conditioning regimens with an increased dose of cyclophosphamide in allogeneic peripheral blood stem cell transplantation for severe aplastic anemia / 中华血液学杂志

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.

Analysis of clinical efficacy of recombinant activated factor Ⅶ on bleeding in patients with hematologic disorders / 中华血液学杂志

Objective@#To investigate the treatment efficacy of recombinant activated factor Ⅶ (rFⅦa) for bleeding among patients with hematologic disorders.@*Methods@#A total of 38 times of bleeding in 31 patients with hematological disease treated with rFⅦa were analyzed retrospectively.@*Results@#The clinical effective rate of rFⅦa for bleeding management in acquired hemophilia A (AHA) patients/hemophilia patients with inhibitor, acute promyelocytic leukemia (APL) patients and patients with non-APL leukemia was 90% (9/10) , 71.4% (5/7) and 60.0% (3/5) , respectively, which was higher than that in patients following HSCT (30.8%) . The clinical effective rate of rFⅦa for patients with bleeding score of 2 (100.0%) was higher than that with 3 (66.7%) and 4 (54.1%) . The effective rate of rFⅦa was 25.0% (2/5) in 5 patients with cerebral hemorrhage, 66.7% (6/9) in 9 patients with hematuria and 41.7% in 12 patients with gastrointestinal hemorrhage. The curative effect for 3 patients with joints and muscle bleeding and 5 patients with skin, nasal, pharyngeal and gum bleeding was excellent. Following HSCT, among patients with bleeding score of 4 points, high dose and repeated use of rFⅦa did not necessarily achieve a good effect. Among AHA/hemophilia patients with inhibitors and patients with acute leukemia who had bleeding score of 4 points, the use of low dose FⅦa could achieve good therapeutic effect, however the efficacy of lowest dose (22.5 μg/kg) rFⅦa was poor.@*Conclusions@#The hemostasis efficacy of rFⅦa is affected by various factors such as diseases, bleeding sites, bleeding score and so on. The use of rFⅦa can achieve good efficacy for bleeding management in AHA patients/hemophilia patients with inhibitor, APL patients and patients with non-APL leukemia. However the efficacy of rFⅦa for bleeding of patients after HSCT is poor. Early use of rFⅦa is important for successful hemostatic treatment. Management of underlying condition is as important as hemostatic treatment.

Allogeneic hematopoietic stem cell transplantation for treatment of refractory and relapsed acute myeloid leukemia: outcomes and prognostic factors / 中华血液学杂志

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.

Vascular endothelial injury induced by anti-endothelial cell antibody in allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To clarify the role of endothelial cells (ECs) injury induced by anti-endothelial cell antibody (AECA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Serum immunoglobulin (IgG) from allo-HSCT recipients were purified and incubated with human umbilical vein vascular endothelium (HUVEC) in vitro, then the functional changes and cell apoptosis were tested.</p><p><b>RESULTS</b>After incubation with AECA positive IgG, soluble adhesion molecules significantly elevated in culture supernatant. When concentration of IgG was 160, 320, and 640 μg/ml, concentrations of soluble intercellular adhesion molecule-1 in supernatant were statistically higher in AECA positive groups [(117.10 ± 12.82) vs (78.17 ± 4.90) pg/ml, (151.30 ± 15.35) vs (89.46 ± 6.02) pg/ml, (239.00 ± 32.53) vs (127.80 ± 13.86) pg/ml, P<0.01)]. When concentration of IgG was 40, 80, 160, 320, and 640 μg/ml, concentrations of soluble vascular cell adhesion molecule-1 in supernatant were also statistically higher in AECA positive groups [(38.51 ± 3.76) vs (24.78 ± 2.59) pg/ml, (61.34 ± 6.99) vs (38.20 ± 3.17) pg/ml, (135.60 ± 24.46) vs (63.73 ± 5.08) pg/ml, (221.30 ± 29.40) vs (112.80 ± 8.91) pg/ml, (420.90 ± 31.70) vs (224.40 ± 20.79) pg/ml, P<0.01]. Clotting activity factors also elevated in culture supernatant after incubation with AECA positive IgG. When concentration of IgG was 80, 160, 320, and 640 μg/ml, concentrations of von Willebrand factor were statistically higher in AECA positive groups [(19.51 ± 0.72) vs (17.17 ± 0.60) ng/ml, P=0.0193; (22.97 ± 1.18) vs (18.27 ± 0.61) ng/ml, (26.40 ± 1.54) vs (19.53 ± 0.70) ng/ml, (34.35 ± 1.60) vs (23.81 ± 0.92) ng/ml, P<0.01]. When concentration of IgG was 320 and 640 μg/ml, concentrations of thrombomodulin were statistically higher in AECA positive groups [(57.50 ± 4.50) vs (40.31 ± 4.39) pg/ml, P=0.0132; (59.18 ± 4.11) vs (38.84 ± 5.16) pg/ml, P<0.01]. However, inflammatory factors (IL-1β, IL-6, IL-8 and ANG2) were not statistically different in AECA positive and negative groups (P>0.05). Moreover, IgG from AECA positive samples did not change the proliferation or cell apoptosis.</p><p><b>CONCLUSION</b>AECA from allo-HSCT recipients dysregulates ECs' function in vitro, but do not induce apoptosis, which is valuable in the pathophysiology of graft-versus-host disease (GVHD) and other complications after allo-HSCT.</p>

Outcomes of adults with Ph-negative B-cell acute lymphoblastic leukemia after autologous hematopoietic stem cell transplantation and the significance of minimal residual disease / 中华血液学杂志

<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>