The 39th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT 2013) was held in London,UK from 7 to 10 April,2013.The meeting received more than 1000 submitted papers,covering leukemia,lymphoma,aplastic anemia,cellular and gene therapies and biology of graft-versus-host disease(GVHD).This review focuses on haploidentical hematopoietic stem cell transplantation (HSCT),improvements of conditioning regimen and early diagnosis and the management of GVHD.

Objective To assess the incidence,risk factors and mortality of acute kidney injury(AKI)in patients with chronic myelogeneous leukemia(CML)after myeloablative allogenetic hematopoietic stem cell transplantation(HSCT). Methods Renal function in 93 CML patients undergone myeloablative allo-HSCT was retrospectively analyzed by the RIFLE criteria. Results Thirty-nine patients (41.9%) developed AKI at a median of 40 days after allo-HSCT, including 24 AKI-R patients(25.8%), 10 AKI-I patients(10.8%) and 5 AKI-F patients (5.4%). The morbidity of AKI in patients with ≥Ⅲ acute graft-versus-host disease (aGVHD) and without ＜Ⅲ GVHD was (81.82±11.63)% and (36.59±5.32)% (P=0.0037)rospectively. The morbidity of AKI in patients with increased total bilirubin and without increased total bilirubin was (72.73±13.43)% and (37.04±5.37)%(P=0.0192) respectively. ≥Ⅲ aGVHD was peor-prognostic factor of AKI and RR was 2.773 [95%CI (1.073-7.167), P=0.035]. RR of AKI-I and AKI-F in patients with ≥Ⅲ aGVHD was 6.320195%CI (1.464-27.291), P=0.013]. The mortality within 100 days after allo-HSCT of patients with AKI was significantly different as compared to patients without AKI (P=0.001). Six-mouth survival rates of different class AKI patients after myeloablative allo-HSCT were (86.96±7.02)% (AKI-R), (70.00±14.49)% (AKI-I), 0 (AKI-F) (P=0.000)respectively. Conclusions AKI is one of the main complications in CML patients after myeloablative allo-HSCT. ≥Ⅲ aGVHD and increased total bilimbin are poor-prognostic factors of AKI, and higher morbidity of AKI-I and AKI-F can be found in patients with ≥Ⅲ aGVHD. With the deteriorated AKI, 6-month survival is decreased. RIFLE criteria is sensitive to the early diagnosis of renal function. Moreover RIFLE can monitor the progression of AKI and predict the clinical outcome.

Objective To analyze morbidity and prognosis of acute kidney injury (AKI) in patients with acute leukemia after myeloablative allogenetic hematopoietic stem cell transplantation (HSCT).Methods Renal function and related clinical data in 66 patients receiving myeloablative alloHSCT were retrospectively analyzed.Renal function was evaluated by RIFLE criteria,which defines AKI as three grades of severity-risk (AKI-R),injury (AKI-I) and failure (AKI-F).Results Thirtyseven recipients (56.1%) developed AKI at a median of 29 days after allo-HSCT,including AKI-R(19 recipients,28.8 %),AKI-I (11 recipients,16.7 %),AKI-F (7 recipients,10.6 %).Compared with baseline value,serum creatinine level in the recipients was significantly increased at the 21st day after transplantation (P＜0.05).During 100 days after HSCT,the morbidity of AKI-F in recipients with HVOD and without HVOD were respectively (55.56 ± 22.22)% and (9.01 ± 4.75)% (P＜0.01).The morbidity of AKI in recipients with or without increased total bilirubin was respectively (68.75 ± 24.54)% and (8.38 ± 4.17)% (P＜0.01).The morbidity of AKI in recipients with or without increased CsA concentration was respectively (66.67 ± 10.29) % and (44.44 ± 8.28) % (P＜0.05).100-day survival rate in recipients after myeloablative allo-HSCT without AKI,with AKI-R,AKI-I and AKI-F was respectively (89.66 ± 5.66) %,(83.88 ± 8.54) %,(81.82 ± 11.63) % and (42.86 ± 18.7) % (P＜0.05).Conclusion AKI is one of the main complications in patients with acute leukemia after myeloablative allo-HSCT.The influence of different class AKI on the mortality was different.The earlier diagnosis,prophylaxis and treatment of AKI by the RIFLF criteria might increase the survival rate in recipients with HSCT.

Objective To analyze the outcomes and the prognostic factors of hematopoietic stem cell transplantation (HSCT) in combination with imatinib for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Methods All 32 patients with Ph+ ALL achieved hematologic complete remission (CR) at time of transplantation, including 27 cases in the first CR (CR1) and 5 in CR2. Nineteen patients achieved molecular remission (MR). Among 32 patients, 4 received autologous HSCT (AHSCT), and 28 allogeneic HSCT (allo-HSCT). The conditioning regimens comprised of total body irradiation (TBI), cyclophosphamide, fludarabine and cytarabine. The median number of transfused mononuclear cells was 5. 6 × 108/kg, and that of CD34+ cells was 2. 94 × 106 /kg. Thirty-one patients were administrated imatinib orally before transplantion, at a dose of 400～600 mg/day, and 16 patients after transplantation, including 7 for prevention at a dose of 300～400 mg/day and 9 for salvage treatment at a dose of 400 ～ 600 mg/day. Results Hematopoietic reconstitution was achieved in all 32 patients. Three-year estimate of overall survival (OS) was (62. 1±8. 6)%, leukemia-free survival (LFS) (59. 2 ± 8. 7)%, relapse rate (RR) (17. 7 ± 7. 2)% and transplant-related mortality (26. 2 ± 8. 0) %. All 4 undergoing AHSCT were alive, and 3 out of them were in continuous CR with durations of 14, 18 and 67 months respectively. The univariate analysis for prognosis in allo-HSCT showed that the OS of HLA-matched sibling donors group was 76. 5 %,higher than that of unrelated or haploidentical donors group (27. 3 %, P＜0. 05), and so was LFS (70. 6 % vs 27. 3 %, P＜0. 05). RR in patients achieving MR at time of transplantation was 5. 6 %,lower than that in those not achieving MR (40. 0 %, P＜0. 05). RR in patients in CR1 at time of transplantation was 12. 5 %, lower than that in those in CR2 (50 %, P ＜0. 05). Conclusion Imatinib improved the outcomes of HSCT for Ph+ ALL, especially to patients achieving MR at time of transplantation and transplantation in early stage (CR1).

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.

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.

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.

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.

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.

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.