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  • American Society of Hematology  (25)
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  • 1
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4501-4501
    Abstract: Introduction Pre-engraftment syndrome (PES) is a common immune reaction prior to neutrophil engraftment after unrelated cord blood transplantation (UCBT), with a unique clinical manifestation of non-infectious fever and skin rash. The reported incidence of PES ranges from 20% to 78%. Although many researchers believe that PES is associated with a high incidence of acute graft-versus-host disease (GVHD) but not with transplant-related mortality (TRM) , relapse, or overall survival (OS), they did not stratify the risk factors of PES, and how to carry out different doses of methylprednisolone (MP) stratified intervention therapy still remains unknown. Method s First, 136 hematological malignancy patients treated with UCBT from April 2000 to February 2012 in our transplantation center were retrospectively analysis. Among them, 92 patients occurred PES. High-risk factors for 180-day TRM in PES patients were established by univariate and multivariate analysis. Then, from January 2013 to August 2016, 221 PES patients were scored according to the risk scoring system and stratified treated with different doses of MP. Finally, in order to validate the efficacy of MP stratification treatment, we conducted a prospective, open label and non-randomized clinical trial including 240 PES patients who underwent UCBT from September 2016 to December 2018. This trial is registered at www.chictr.org.cn as ChiCTR-ONC-16009013. Results The cumulative incidence of neutrophil and platelet engraftment was significantly higher in PES group than non-PES group (97.8% vs 70.5%, P 〈 0.001; 75.0% vs 54.5%, P=0.05). In 92 PES patients, multivariate analysis showed that failed MP treatment, multiple clinical symptoms and early onset of PES were independent high risk factors affecting180-day TRM. One high risk factor was scored as 1. The 92 PES patients were divided into PES-0, PES-1,PES-2 and PES-3, and the higher the score, the higher the TRM (17.7% vs 21.9% vs 62.5% vs 100%,respectively; P 〈 0.001), and the lower the OS (68.3% vs 56.2% vs 25.0% vs 0%, respectively; P 〈 0.001). Then, from January 2013 to August 2016, 221 PES patients were scored as PES-0, PES-1 and PES-2 according to the following two high risk factors (multiple clinical symptoms and early onset of PES) and stratified treated with different doses of MP (0.5mg/kg/d for PES-0, 1mg/kg/d for PES-1 and 2mg/kg/d for PES-2). Compared to the previous PES patients with the same risk score, the 180-day TRM of PES-1 and PES-2 patients was significantly reduced and the OS, disease free survival (DFS), and GVHD-free and Relapse-free survival (GRFS) were significantly increased after stratified treatment. The results in the prospective trial were similar to the retrospective study. In addition, although stratified therapy could significantly improve the prognosis of PES-2 patients cohort, the cumulative incidence of acute GVHD and GRFS are still the worst compared with other risk score patients. Therefore, how to improve the outcomes of PES-2 patients remains to be further studied. Conclusion s PES after UCBT is benefit for engraftment, but should be graded according the risk scoring system. Different doses of MP stratified intervention therapy can significantly improve the prognosis of severe PES patients. The risk scoring system of PES after UCBT and MP stratification treatment are worthy of clinical application. But the cumulative incidence of acute GVHD and GRFS in severe PES patients still need to be ameliorated in the further study. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1222-1222
    Abstract: Introduction : Unrelated cord blood transplantation (CBT) is one of the most promising curative treatment modalities for hematological malignancies. But the data was limited in China. This retrospective study evaluated the clinical outcomes of intensified myeloablative unrelated CBT for high-risk or advanced hematological malignancies in our single center. Patients and Methods: From September 2006 to December 2013, Total of 187 high-risk or advanced hematologic malignancies underwent intensified myeloablative unrelated CBT. All CBT patients received a myeloablative conditioning regimen of TBI/Ara-C/CY [total body irradiation (TBI, total 12 Gy, 4 fractions) (d-7, d-6) arabinoside cytarabine (Ara-C) (2.0g/m2 every 12h for 2 days) (d-5, d-4) and cyclophosphamide (CY, 60 mg/kg daily for 2 days) (d-3, d-2)] (age≥14 years or primary induction failure or no remission after relapse), or Fludarabine/BU/CY2 [fludarabine (Flu, 30mg/m2 daily for 4 days) (d-8~ -5), busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)] (For lymphoid malignancies patients with age <14 years or prior radiotherapy which would presuppose a high risk of toxicity), or Ara-C/BU/CY2 [ Ara C (2.0g/m2 every 12h for 2 days) (d-9, d-8), (busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)](for myeloid malignancies patients with age 〈 14 years or prior radiotherapy which would presuppose a high risk of toxicity), and G-CSF was given with 5 ug/kg daily by subcutaneous injection one day prior to Ara-C with 3 days. For GVHD prophylaxis, all patients were given a combination of cyclosporine and short-course mycophenolate mofetil, and no patient received antithymocyte globulin (ATG). Results: Total of 181 patients (97.3%) achieved neutrophil engraftment and platelet engraftment, and the median number of days was 18 days (range 12~37 days) and 37.5days (range 15~112 days), respectively. Total nucleated-cell dose (≥5.2×107 / kg) and total CD34+ cell dose (≥3.8×105 / kg) were the favorable factors predicting for a higher probability of neutrophil engraftment (p =0.012, 0.025). The cumulative incidence of pre-engraftment syndrome (PES) and day-100 grade Ⅱ-Ⅳ acute GVHD was 75.4% (95% CI, 65.2-84.2%) and 28.34% (95% CI, 28.13~28.55%), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD 100 days after transplantation was 32.6% (95% CI, 42.3-22.8%)in the PES group and 15.2% (95% CI, 8.3-22.6%) in the non-PES group (р=0.016). Multivariate analysis showed that BU/CY2 based conditioning and without PES were significant risk factors for graft failure [RR=2.34 (95% CI, 1.32- 6.12), p =0.015; RR=2.89 (95% CI, 1.25- 6.82), p =0.009]. The median follow-up time was 27(7~89)months. Transplant-related mortality at 180 days and relapse at 3 years after CBT was 24.9% (24.7~25.2%) and 14.7% (14.6~14.9%). Probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 61.2% (95% CI, 51.3%- 72.3%) and 58.6% (95% CI, 49.5%- 67.9%), respectively. For pediatric patients, 3-year OS and DFS were 66.2% (95% CI, 56.4%- 75.8%) and 64.8% (95% CI, 54.6%- 74.2%); for adult patients, 3-year OS and DFS were 54.5% (95% CI, 45.8%- 63.7%) and 50.3% (95% CI, 41.5%- 60.1%), respectively. Conclusions: To the best of our knowledge, this is the largest clinical study of unrelated CBT reported in China. This retrospective study indicates that intensified myeloablative CBT procedures are associated with significant favorable outcomes in survival advantage in high-risk or advanced hematological malignancies. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 3
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4818-4818
    Abstract: Relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) has poor long-term survival even after chimeric antigen receptor (CAR)-T cell therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several studies supported that CAR-T therapy followed by allo-HSCT is benefit for improving long-term leukemia free survival (LFS). Since probably a stronger graft versus leukemia (GVL) effect of unrelated cord blood transplantation (UCBT), it is uncertain whether consolidative UCBT is suitable for R/R B-ALL after CAR-T therapy. Here, we conducted a retrospective comparative study for R/R B-ALL patients receiving UCBT in our transplantation center. Totally 43 cases with R/R B-ALL who underwent UCBT were assigned to CAR-T group (patients achieved CR or CRi by CAR-T cell therapy before bridging to UCBT, n = 21) or non-remission (NR) group (n = 22). The median time from CAR-T infusion to UCBT was 62 (range, 42-185) days. All patients achieved neutrophil engraftment by day 42 in CAR-T group. The 180-day cumulative incidence of platelet engraftment was higher in CAR-T group than in NR group (90.5% vs 65.7%, P = 0.16). Incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) were 28.6% and 23.8% in CAR-T group, which were both tendency lower than in NR group (45.5% and 31.8%, P = 0.32 and P = 0.63, respectively). No patient suffered from extensive chronic GVHD in CAR-T group, which was lower than in NR group (9.1%, P = 0.23). Lower 2-year cumulative incidence of transplant-related mortality (TRM), and higher probabilities of 2-year overall survival, leukemia free survival (LFS), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) were found in CAR-T group (4.8% vs 28.2%; 75.0% vs 37.7%; 49.8% vs 23.0%; 42.4% vs 14.8%; P = 0.037, 0.005, 0.028 and 0.017; respectively). However, 2-year cumulative incidence of relapse was comparably high between CAR-T and NR group (26.7% vs 38.3%; P = 0.41). CAR-T therapy followed by UCBT has a superior survival for R/R B-ALL, but remains relatively high post-transplant relapse rate. Prevention of relapse after UCBT is warranted in this patient cohort. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 4
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2683-2683
    Abstract: 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 and close follow up) and 〉 = 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( 〈 10^3/mL) group. There were 63 males and 63 females with a median age of 13 years(range,1-52) and a median weight of 40 Kg (range,11-87) .The median follow-up time among survivors was 736 days (range, 100-2184).Univariate and multivariate analysis showed, high CMV load group has lower two-year cumulative incidence of relapse [(2.9% vs. 17.9%, P=0.017); adjusted HR 0.19, P=0.045], higher cumulative incidence of DFS [(88.3% vs. 63.2%, P=0.003), adjusted HR0.28, P=0.005] ,higher cumulative incidence of OS[(88.0% vs. 72.3%, P=0.037),adjusted HR0.35,P=0.027]. The immune reconstruction data of the two groups showed that the median value of CD8+ T cells in the high CMV load group at 1, 4, 6, 9, 12, 15, 18 and 24-36 months after transplantation was higher than the low CMV load Group (30.3% vs. 13.9%, 46.8% vs. 27.6%, 46.5% vs. 27.9%, 37.0% vs. 31.5%, 37.7% vs. 20.9%, 42.3% vs. 22.8%, 30.4% vs. 23.5%, 29.1% Vs.22.1%; P=0.032, P=0.014, P=0.01, P=0.621, P=0.005, P=0.008, P=0.088, P=0.371). Conclusion: Higher CMV load within 100 days after UCBT presents lower relapse,improved OS and DFS in AML patients. At the same time, the proportion of CD8+ T cells increased significantly in patients with high CMV load after 1, 4, and 6 months after transplantation. The above data indicates that CMV virus infection may stimulates the activation of CD8+ T cells further induces a GVL effect. keywords:Cytomegalovirus,acute myeloid leukemia,cord blood transplantation,virus load, relapse. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 5
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 1-2
    Abstract: BACKGROUND Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the main cause of treatment failure for patients with acute myeloid leukemia (AML). Conventional treatments such as donor lymphocyte infusions (DLI) or secondary allo-HSCT as a monotherapy or in combination with novel agents or immunotherapy showed limited improvements on long-term survival. Our previous studies have shown that a rare subset of CD4- and CD8- double negative T cells (DNTs) expanded from periphery of healthy donors are effective in targeting AML cells in vitro and in xenograft models. Also, allogeneic DNTs can be used as an off-the-shelf adoptive cellular therapy (ACT) for AML. We undertook a first in-human phase I/IIa trial to assess the safety and efficacy of escalating doses of DNTs for the treatment of AML patients relapsed post allo-HSCT. This study protocol was approved by Chinese Ethics Committee of Registering Clinical Trials. Informed consent was obtained in accordance with the Declaration of Helsinki. The trial was registered on the Chinese Clinical Trial Registry (ChiCTR-IPR-1900022795). METHODS From June 2019 to June 2020, 12 patients with relapsed AML after allo-HSCT were enrolled in the trials. Three patients received HLA-matched sibling stem cell transplant, and 9 patients received umbilical cord blood transplantation (UCBT). Hematological relapse was found in 9 cases, and molecular relapsed in 3 cases. None of the patients were able to obtain DLI from previous donors for various reasons. Clinical-grade DNTs from peripheral blood of healthy donors were expanded. After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, each patient received three infusions of HLA-mismatched DNTs expanded from healthy volunteers at escalating doses of 5×107, 1×108, or 2-4×108 per kilogram of body weight at one week interval. Numbers of total DNTs and donor-derived DNTs, inflammatory cytokines levels in vivo were measured according to the study protocol. Post-remission therapy was permitted 14 days after the last DNTs infusion according to treating physician's discretion. RESULTS All surviving patients were followed until August 1st, 2020. At a median follow-up of 4.3 months (range 1.7 to 12.2 months), 1 patient withdrew from the trial after the second DNT infusion for a personal reason. 6/11 patients (54.5%) achieved complete response (CR) with 5 of these patients negative for (45.4%) minimal/measurable residual disease (MRD). 4/11 patients (36.3%) achieved partial remission. Up to the last follow-up, 4/11 patients remain CR. Increase in the levels of serum inflammatory cytokines, including interleukin (IL)-6, TNF-alpha, MCP-1, and MIP-1-beta over baseline were observed without signs of cytokine release syndrome, neurotoxicity, or graft-versus-host disease. The most common adverse events related to DNTs treatment were fever and headache. None of the patients showed & gt;grade 2 adverse event (AE). The maximum tolerated dose was not reached. Donor DNT cell expansion was detected as early as 6 hours after infusion and reached the peak at 24 hours after the 1st infusion in most patients, slightly increased after the 2nd and 3rd infusions, and lasted for 2 weeks after 3rd infusion. However, total DNTs increased and reached the peak at 2 weeks after 3rd infusion. CONCLUSIONS Our results show that allogeneic DNTs therapy is safe, well tolerated, and potentially effective in treating AML patients who relapsed after allo-HSCT. The total number of DNTs increased after infusion. Compared to other agents, DNTs more effectively induced complete responses in this patient population. Our on-going study is to elucidate the mechanism of DNTs-mediated leukemia clearance, and explore the use of DNTs as carrier for Chimeric Antigen Receptor or transgenic TCR to further enhance the efficacy targeting resistant AML cells. Disclosures Zhang: AbbVie: Current equity holder in publicly-traded company; University Health Network: Consultancy, Current equity holder in private company, Other: Principal Investigator, Patents & Royalties.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 6
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2055-2055
    Abstract: Objective In contrast to solid organ transplantation, ABO blood group incompatibility was acceptable in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, reports of the effect of donor-recipient ABO incompatibility on long-time survival, graft-versus-host disease (GVHD), and relapse after allo-HSCT were controversial. Relatively few reports existed on the effects of ABO incompatibility after umbilical cord blood transplantation (UCBT). The aim of this study was to investigate the role of major ABO incompatibility on RBC transfusion burden, hematologic recovery, GVHD, transplant-related mortality (TRM), relapse, and overall survival (OS) in UCBT for malignant disease. Methods This retrospective study included 587 malignant hematonosis patients who received myeloablative single-unit unrelated donor UCBT at our center between May 2008 and June 2018. Median follow-up time of the patients alive was 40.7 months (range: 12.0-134.6 months). A total of 230 (39.2%) patients received an ABO-identical transplant, and 357 (60.8%) received ABO-mismatched transplants, including 161 (27.4%) minor, 141 (24.0%) major, and 55 (9.4%) bidirectional ABO-incompatible UCBTs. All patients received myeloablative conditioning regimens and cyclosporine A (CsA) combined with mycophenolate mofetil (MMF) as a GVHD prophylaxis. Results A comparison of ABO compatibility and incompatibility demonstrated no significant differences (P 〉 0.05) in the cumulative incidence of neutrophil, platelet, and red blood cell engraftment . There was no significant difference in the cumulative incidence of grades Ⅱ to Ⅳ aGVHD (P= .527) and Ⅲ to Ⅳ aGVHD (P= .949) among the 4 groups (Figure A , B). In univariate analysis, ABO blood group incompatibility was not associated with cumulative incidence of 180d TRM (Figure C, P= .602). The overall 3-year survival had no statistically significant differences among the 4 groups (Figure D; P= .384). Further, 11 patients were excluded from the analysis of post-UCBT RBC transfusion burden because of missing data and non-red blood cell engraftment. Of the remaining 576 patients, the median number of RBC transfusions during transplant days 0 to 60 was 4 (range, 0 to 106). There was no significant difference in the transfusion burden among all ABO blood type mismatch groups (Table 1, P = .069). Furthermore, none of the patients developed pure red aplastic anemia (PRCA) after UCBT. Conclusion The results showed that ABO blood group incompatibility had no significant impact on hematologic engraftment, the occurrence of GVHD, and the survival of malignant hemoblastosis. Patients with myeloablative single-unit UCBT may not develop PRCA; Donor-recipient ABO incompatibility may not be the major consideration in the selection of umbilical cord blood. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 7
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3284-3284
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 8
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5709-5709
    Abstract: 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 〈 .001). Of them, 200 patients received Cy/TBI, and 131 patients received IV Bu/Cy. The median dose of infused total nucleated cells were 4.51(range, 2.19 to 12.06 )× 107/kg and 3.77(range, 2.14 to 9.05)(P 〈 .001), respectively. And the median number of CD34+ cells was 2.61(range, 0.91 to 9.64) ×105/kg and 2.01(range, 1.12 to 8.71)(P 〈 .001), respectively. The median times to neutrophil engraftment were 16 days and 19 days(P 〈 .001). The estimated DFS at 3 years were not statistically different between the conditioning regimens in univariate analysis. 63.9%±4.21% in patients undergoing conditioning with IV Bu/Cy and 54.4%±3.57% in patients undergoing conditioning with Cy/TBI(P = .21).These results were similar in multivariable analysis (HR, 1.03; 95% CI, 0.68 to 1.54; P = .905). Univariate analysis and multivariable analysis demonstrated that estimated OS and GRFS at 3 years were also not different between those two conditioning regimens. Our resluts demonstrates that, compared with TBI, IV Bu regimen was associated with a higher incidence of graft rejection in CBT. But there was no difference in survival with no increased risk for NRM or relapse between two regimens. For those centers lack of radiation facilities, IV Bu may be a valid and efficient alternative to TBI. With the restriction of a retrospective registry analysis and limited patient munbers, rigorously designed prospective randomized controlled trials are needed to further investigated the availability of IV Bu and TBI for CBT. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 9
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2275-2275
    Abstract: Aim The European Group for Blood and Marrow Transplantation (EBMT) risk score has been implemented as an important tool to predict patient outcomes following allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, to our knowledge, this score has never been applied in cases of single umbilical cord blood transplantation (sUCBT). The aim of this study was to assess the capacity of the EBMT risk score in predicting the outcomes of patients with leukaemia receiving sUCBT. Methods We retrospectively analysed 218 consecutive patients with leukaemia who received sUCBT at our centre between February 2011 and December 2015. Sixty-eight of the 218 patients had AML, 137 had ALL, 10 had CML, 2 had mixed phenotype AL, and only one patient had plasma cell leukaemia. The median age was 12 years (range, 1-46 years), and the median weight was 40 kg (range, 10-100 kg). All of the patients received an intensified myeloablative conditioning regimen with cyclosporine A (CsA) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis. All of the patients were followed until 31 March 2016, with a median follow-up of 10.7 months (range, 0.5-58.9 months). Results The overall survival (OS) and leukaemia-free survival (LFS) of the entire cohort were 66.8% and 55.4%, respectively, whereas the cumulative incidences of relapse rate and non-relapse mortality (NRM) were 22.4% and 18.0%, respectively. In the univariate analysis, a higher EBMT risk score was associated with worse OS, worse LFS, lower NRM and higher relapse rate, ranging from 80.2%, 74.5%,7.5% and 18.0%, respectively, for patients with a score of 1 to 21.8%, 17.0%, 27.3% and 55.7%, respectively, for patients with a score of 5/6. Hazard ratios of the four indexes all steadily increased for each additional score point. Importantly, the prognostic value of the EBMT risk score on OS, LFS, NRM and relapse was maintained in the multivariate analysis. Moreover, considering the importance of allele-level HLA matching, we developed a modified sUCBT-EBMT risk score using HLA matching situations instead of donor type and found that the modified score could also be used as a predictor for patient outcomes following sUCBT. Conclusions The EBMT risk score is a good predictor of outcomes of patients with leukaemia following sUCBT. The modified sUCBT-EBMT risk score can also be used as a pretransplant risk assessment, but this metric still requires further evaluation with a larger cohort. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4525-4525
    Abstract: Abstract 4525 To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) using total body irradiation (TBI)-based myeloablative conditioning regimen without antithymocyte globulin (TBI/Ara-c/CY w/o ATG) in adolescent and adult patients with high-risk hematological malignancies. Outcomes of forty-five consecutive adolescent and adult patients with high-risk hematological malignancies treated with TBI-based myeloablative UCBT without ATG in a single center between September 2006 and February 2012 were retrospectively analyzed. The conditioning regimen included TBI/Ara-c/CY:TBI 12GY (four fractionated) + Ara-C 8g/m2 (two days fractionated) + CY 120mg/kg (two days fractionated), and rhG-CSF was administered for myeloid leukemia by continuous infusion at a dose of 5μg·kg−1·d−1. Infusion of G-CSF was started 24 hours before the first dose of Ara-C and stopped at the completion of the last dose. The patients included 31 males and 14 females, with a median age of 21 years (range: 14–40) and a median weight of 58 kg (range: 42–76). Of those, 17 patients (37.8%) had advanced disease. Double UCB grafts were used for 16 patients, while single UCB graft was used for 29 patients. The median number of nucleated cells infused was 3.57 (1.94∼6.76)×107/kg and the median CD34+cells infused was 2.11 (0.71∼4.95)×105/kg. All patients received a combination of cyclosporine (CSA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. All patients successfully engrafted. The median times to neutrophil (ANC≥0.5×109/L) and platelet (PLT PLT≥20×109/L) recovery were 19 days (range: 13–35 days) and 36 days (range: 24–90 days) respectively after transplantation in 40 evaluable patients. Acute GVHD occurred in 21 patients and the cumulative incidences of gradeII-‡W and grade III-‡W acute GVHD were 24.4% and 11.1%, respectively. Chronic GVHD occurred in five of 40 evaluable patients (12.5%). Of the 45 patients, 9 (20%) had relapse. After a median follow-up of 25.1 months (range: 6–65.1) among survivors, treatment-related mortality (TRM) within 100 days and within one year was 8.9% and 24.4%, respectively. The main causes of death were pneumonia and severe acute GVHD. The probability of three-year disease-free survival and overall survival (OS) was 53.3% and 57.8%, respectively. The TBI/Ara-c/CY myeloablative conditioning regimen has been well tolerated by patients at our institution and seems to be able to establish sustained donor cell engraftment and decrease the risk of transplant-related death. For high risk patients and patients with advanced disease, this conditioning regimen could reduce relapse and chronic GVHD, indicating the feasibility of TBI/Ara-c/CY as a conditioning regimen for CBT in adolescent and adult patients with hematologic malignancies. Disclosures: Sun: Key Scientific and Technological Project of Anhui province “Twelfth Five-Year Plan” (11010402164): Research Funding; the Fund of the Key Medical Project of Anhui Provincial Healthy Department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program (2009): Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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