ALBERT

Description: Introduction: Natural killer (NK) cells are important part of the innate immunity defense system and play an antiviral, anti-tumor and immunomodulatory role in the body's immune response. NK cells are the first lymphocytes recovered after umbilical cord blood transplantation (UCBT). By attacking on the host cell, leukemia cells and antigen-presenting cells, the allogeneic reactive NK cells help realize successful implantation, mediate Graft-versus-leukemia (GVL) to reduce the recurrence, and lower the incidence of graft versus host disease (GVHD) respectively, thereby improving overall survival (OS) ultimately. The effect is based on the interaction of killer-cell immunoglobulin-like receptors (KIR) of donor NK cells with ligands of the major histocompatibility complex found on the surface of the target cells. HLA-C1 subtypes provide the ligand for KIR2DL2 and KIR2DL3, and the HLA-C2 subtypes for KIR2DL1. Therefore, we want to study the impact of the killer cell immunoglobulin like receptor/human leukocyte antigen(KIR/HLA) receptor ligand model in UCBT Method: Between July 2012 and June 2018, 270 patients with malignant hematologic disease receiving single-unit UCBT were divided into two groups based on the absence or the presence of one of the C-ligands for inhibitory KIR. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR present on UCB NK cells, (patients homozygous C1/C1 or C2/C2). Group 2 (n=96) patients had heterozygous C1/C2 in which KIR-mediated GVL effect was not expected (presence of both C ligands for inhibitory KIR in the receptor). Group 1 (mean age 13y, r 1-62; male 90) and group 2 (mean age 14.5y, r 1-59; male 56) had no significant differences in age, gender, weight, underline diseases, state of disease, and HLA match (low-resolution). All patients' conditioning regimen was myeloablative and did not contain anti-thymocyte globulin (ATG). Cyclosporine combined with mycophenolate mofetil was applied as GVHD prophylaxis. Results: The median follow-up time since the transplant for the surviving patients was 25 months (11-84 months). We compared some indicators related to UCBT between the two groups. The median time to neutrophil engraftment for group 1 and 2 was 16 days vs. 17 days (P = 0.705), and median time to platelet engraftment was 35 days vs.38.5 days (P = 0.317). The cumulative incidence of II-IV acute GVHD in 100 days was 42.5% (38.7% for group 1 vs. 50.0% for group 2, P = 0.0751), but multi-variate analysis showed that HLA-C ligand absence was an independent risk factor for II-IV acute GVHD after transplantation (HR=1.5280, P=0.0356). Patients with absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2):17.7% VS 22.7% at 3 years (P=0.288). The 3-year OS was 69.3% for group 1 and 60.5% for group 2 (P=0.0792). Non-relapse mortality for group 1 was 16.8% and for group 2 was 20.8% (P=0.328). There was no statistically significant difference between the two groups in 3-year disease-free survival (64.9% vs 55.4%, P=0.0819). Conclusion: Our results suggest that patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades II-IV acute GVHD after UCBT. The absence of HLA-C ligands in recipients had no statistically significant effect on other transplant survival prognosis, which may be related to the conditioning regimen without removing T cells. A beneficial impact mediated by NK alloreactivity between UCB and recipient may be observed during longer follow-up. Therefore, the absence of a C-ligand could be considered as one of the critical factors for the selection of UCBT. No conflict of interest to declare. Disclosures No relevant conflicts of interest to declare.

Description: Background: Umbilical cord blood transplantation (UCBT) is an alternative to matched-unrelated or mismatched-related peripheral blood (PB) or BMT and has emerged as a widely accepted treatment for a wide variety of hematologic malignancies. However, delayed platelet engraftment (DPE) and platelet engraftment failure still remain the common problems following UCBT. So far, no standard therapy has been recommended. A few studies have demonstrated that recombinant human thrombopoietin (rHuTPO) could play an effective role in advancing platelet recovery after allo-HSCT. Nevertheless, it remains unknown whether rHuTPO plays the same role while it is applied in UCBT. We designed this prospective randomized controlled trial with the purpose of determining whether rHuTPO improves platelet engraftment in patients undergoing single UCBT(sUCBT) and further evaluating the function of rHuTPO in sUCBT. Methods: We enrolled 120 patients with haematological malignancies between October 2016 and March 2018 undergoing sUCBT in Department of Hematology, the First Affiliated Hospital of University of Science and Technology of China. This study was supported by National Natural Science Foundation, China (81670165) and International Cooperation Projects of Anhui Province, China(1804b06020352). The trial was approved by the Medical Ethics Committee of the First Affiliated Hospital of University of Science and Technology of China, and registered on www.chictr.org.cn(ChiCTR-IPR-16009357). 60 patients were randomly assigned into the experimental group, in which they received rHuTPO on Day 14 after sUCBT with a dose of 300 U/kg once daily for a period of 14 days; the remaining 60 patients formed the no-treatment control group. Among 120 patients, 19 received total body irradiation (TBI) based conditioning and others received modified myeloablative conditioning without antithymocyte globulin (ATG) as myeloablative conditioning. All patients were given cyclosporin (CsA) and mycophenolate mofetil (MMF) preventing graft-versus-host disease (GVHD). Supportive care and other treatments, including infectious disease prophylaxis and the use of granulocyte colony-stimulating factor, were provided following our center's protocols. Results: With a median follow-up of 336 days (ranging between 96-618) for the surviving patients, the cumulative incidence of PLT engraftment in the rHuTPO group (89.7%, 95% confidence interval [CI], 77-95.5) was significantly higher than that in the control group (78.9%, 95%CI, 65.3-87.6) (p=0.0294); the median time of PLT engraftment was 35 and 40days (ranging between 18-144 and 19-170 respectively, P=0.155). The median time of PLT recovery in the rHuTPO group was 43days(ranging between 25-171days), which was significantly shorter than that in the control group(53days, ranging between 28-195, P=0.034). The rHuTPO group also showed an advantage over the control group in infused PLT units (6 vs 8, p=0.0294). The cumulative incidence of ANC engraftment was 98.3% (95% CI, 75.2-99.9) and 94.9% (95% CI, 83.8-98.5) (p=0.111) respectively in two groups.Multivariate analysis confirmed the significance of differences in platelet engraftment between two groups. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease (GVHD),relapse,non-relapse mortality (NRM) and cytomegalovirus viremia and the probabilities of overall survival(OS) and leukemia free survival (LFS) did not differ between the two groups. No severe adverse effects were observed in all patients. Conclusions: Our results demonstrate that rHuTPO could noticeably improve platelet engraftment and promote platelet recovery in patients with haematological malignancies receiving sUCBT; in the meantime, it could also reduce the requirement for platelet transfusion. This study indicated that rHuTPO could be a good option for promoting platelet engraftment and recovery in haematological malignancies after sUCBT. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Description: Early immune disorders, including preengraftment syndrome (PES)and acute graft-versus-host disease(aGvHD)are problematic in cord blood transplantation (CBT), and optimal prophylaxis has not been established. Here, we prospectively investigated whether intensive GvHD prophylaxis by adding low-dose methotrexate (MTX)at day 3 after CBThas a prognostic impact on CBT. 16 consecutive single-unit CBT recipients treated for high-risk hematologic malignancies (10 cases) and non-malignancies (6 cases) between February 2019 and March 2019. The patients, 6 female and 10 males, had a median age of 9 years (range 4-40) and a median weight of 26 kg (range 14-68). Myeloablative preparative regimen comprised fludarabine, busulfan and cyclophosphamide for malignancies and reduced-intensity-conditioning comprised fludarabine, cyclophosphamide and total-body irradiation (4 Gy) for non-malignancies. Graft-versus-host disease (GvHD) prophylaxis was cyclosporine and mycophenolate mofetil plus MTX 3 mg/m2 on day+3. 14 patients achieved engraftment at a median of day 19 and had more than 95% (complete) donor chimerism on day+14.Two patients without hematopoietic reconstitution were engrafted after a second CBT. PES was characterized by high-grade fever, rash, pulmonary edema, weight gain, liver and renal dysfunction developed on a median of day 8 in 11 of the 16 evaluable patients, including 2 who did not achieve engraftment. The PES patients received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 2 patients were requiredBasiliximab to improve clinical symptoms. Grade I to IV and aGvHD developed in 4 and only 1 patient developed severe aGvHD with Grade Ⅲ. Follow-up so far, one death occurred at day 103 because of pneumonia. 15 patients are alive well at a median follow-up of 135 days (131-163). Adding low-dose MTX at day +3 may be offer one optimal regimen to reduce severe early immune reactions and improve outcomes in CBT. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for malignant and non-malignant hematological diseases. Chronic Graft-versus-Host Disease (cGVHD) is a major contributor to late morbidity and mortality, significantly affects patients' quality of life.The first-line systemic therapy is corticosteroid,but 40%-60% patients need second-line or additional treatments. Available second-line therapies such as cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus and sirolimus are less than ideal. Ruxolitinib is is an orally selective JAK1 and JAK2 inhibitor that has been approved by the FDA for the treatment of myelofibrosis. Prospective phase II and III trials using Ruxolitinib have demonstrated that it's effective and safe in the treatment of cGVHD. In this report, we share the clinical outcomes of using Ruxolitinib as salvage treatment of cGVHD. Method s This is a retrospective study of 39 patients with cGVHD who received Ruxolitinib as salvage treatment after failure of first-line or second-line therapies given at least one week.All patients were informed of the off-label use of Ruxolitinib and provided informed consent. Patients were treated with Ruxolitinib orally as an add-on immunosuppressive therapy(5mg twice daily if body weight ≥ 25kg and 2.5mg twice daily if body weight

Description: Objective: The aim is to explore the potential relationship between the virus load of Cytomegalovirus (CMV)infection and disease relapse in acute myeloid leukemia (AML)patients after Umbilical cord blood transplantation (UCBT), The mechanism of interaction in which lymphocyte subsets may be involved is also analyzed. Design and method: All 126 patients with acute myeloid leukemia receiving a single UCB graft at the institution between Oct 2010 to Dec 2017 were enrolled in this retrospective study and engraft failure and death within 100 days excluded. All patients received common transplant processing: intensive myeloablative conditioning without ATG, Cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD prophylaxis. All patients had negative plasma CMV DNA prior to the transplantation and examined twice a week for at least 100 days after transplantation. CMV were measured by Quantitative real-time PCR using TaqMan (ABI)-based method. Patients were divided into three groups according to the CMV viral load within 100 days: CMV-negative groups (no relevant special treatment), = 1,000 / mL CMV DNA copy group (reduced immunosuppressor, antiviral treatment and close follow up), the first group was merged into the second group due to the 92% incidence of CMV infection after UCBT .To compare the two regimens which aimed to focus on disease relapse ,non-relapse mortality (NRM),overall survivor (OS),disease free survival(DFS) ,GVHD-free /relapse-free survivor (GRFS)and graft versus host disease (GVHD) after transplantation for two years. Also, retrospectively compared the lymphocyte ratio recovery at different time points after transplantation . Results: Patients characteristic had no significant differences between high CMV virus load (〉=10^3/mL) group and low CMV virus load(

Description: :The aim of this study was to evaluate the Impact of iron overload and iron removal therapy on the outcome of allogeneic hematopoietic stem cell transplantation (SCT) in patients with severe aplastic anemia (SAA). Forty-five transplant patients with SAA were retrospectively analyzed. Patients were divided into two groups according to whether there was iron overload or not: iron overload group (n=23) and non-iron overload group (n=22). The iron overload group had higher 1-year transplant-related mortality (TRM) (30.4% vs. 4.5%, P = 0.02), lower 1-year transfusion-free survival (TFS) (40.6% vs. 81.8%, P = 0.007) and lower 1-year overall survival (OS) (54.8% vs. 90.2%, P = 0.003) than the non-iron overload group. However, there was no significant difference in implantation rate, pre-engraftment syndrome (PES) and acute graft-versus-host disease (aGVHD, grade III-IV) between the two groups. Furthermore, the multivariate analysis revealed that iron overload was an independent risk factor affecting OS (HR = 36.88, P = 0.03). The patients in iron overload group were divided into two subgroups according to the time of iron removal using deferasirox 20mg/kg/d. Specifically, group A (n=17) was treated with deferasirox 20mg/kg/d for 3 months or less and group B (n=6) treated for more than 3 months. The results showed that group B had a lower one-year TRM (0% vs. 41.2% , P = 0.07), higher 1-year TFS (66.7% vs. 31.4%, P = 0.18) and higher 1-year OS (100% vs. 31.4% , P = 0.02) than group A. There were no significant difference in implantation rate, PES and aGVHD ( III-IV) between the two groups. In conclusion, the results indicate that iron overload before transplantation was associated with increased TRM and decreased OS, suggesting that iron overload was associated with worse transplantation outcomes. However, standardized iron removal therapy could reverse the adverse effects of iron overload on the outcomes of transplantation to a certain extent and improve the prognosis significantly. Disclosures No relevant conflicts of interest to declare.

Description: Intravenous busulfan (IV-Bu) or total body irradiation (TBI) based regimens are currently the most widely used myeloablative conditioning regimens for patients with hematologic malignancies undergoing allogeneic stem-cell transplantation(allo-SCT). Numerous trials have been undertaken on the clinical outcomes between IV Bu and TBI, but there are no comparative data for cord blood transplantation(CBT). We conducted a prospective registry-based study to analysis the outcomes of IV Bu and TBI in CBT patients with hematologic malignancies. From May 1, 2008 to Mar 31, 2016, a total of 331 consecutive patients with hematologic malignancies recieved singe unrelated CBT were involved in the study. Eligibility criteria for this analysis included:(1)Weigh ≧35 kilograms and age ≦ 60 years; (2)All patients recieved a single unit CBT but not a double units CBT; (3)Consensus criteria preparative regimens were based on full dose IV Bu(total 12.8 mg/kg, 0.8mg/kg every 6 h for 4 days) or TBI(total 12 Gy, 4 fractions) combined with Cy(60mg/kg × 2d); (4)GVHD prophylaxis regimens include cyclosporine(CSA) and mycophenolate mofetil(MMF) without Antithymocyte Globulin(ATG). Patients who has recieved a previous autologous or allogeneic transplantation was excluded in the study. The cumulative incidence of neutrophil engraftment were 91.6% in IV Bu/Cy cohort and 98.0% in Cy/TBI cohort(P 〈 .001), respectively. The median follow-up time in IV Bu/Cy and Cy/TBI cohorts was 28.7(range, 12.2 to 91.3) months and 55.5(range, 13.1 to 117.1) months, respectively(P