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.

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

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.

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.

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.

Comparison of outcomes of adult acute lymphoblastic leukemia patients underwent autologous and allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<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>

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>

Clinical significance of determining anti-endothelial cell antibodies and thrombopoietin in the differential diagnosis of ITP and SLE / 中国病理生理杂志

AIM: To study the clinical significance of determining serum anti-endothelial cell antibodies (AECA) and thrombopoietin (TPO) in the differential diagnosis of idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE). METHODS: Serum AECA and TPO in 76 patients with ITP, 41 patients with SLE and 50 normal individuals were detected by ELISA method. RESULTS: Serum AECA level in SLE and ITP was much higher than that in normal group (P0.05), but serum TPO level in SLE was much higher than that in ITP and normal groups (P