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  • 11
    In: Blood, American Society of Hematology, Vol. 121, No. 20 ( 2013-05-16), p. 4056-4062
    Abstract: Risk stratification treatment of t(8;21) acute myeloid leukemia may decrease relapse and improve long-term survival. Allo-HSCT benefited high-risk patients, but impaired the survival of low-risk patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 12
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 14 ( 2022-07-26), p. 4320-4329
    Abstract: Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 2876449-3
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  • 13
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 162-162
    Abstract: Abstract 162 Background and Aims. The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) in the first chronic phase (CP) in the imatinib era have not previously been evaluated. This prospective cohort study was designed to compare the medical outcomes and quality of life (QOL), with imatinib versus allo-HSCT from an HLA-matched sibling donor for CML in the first CP including the early CP (ECP; a CML duration 〈 12 months) and the late CP (LCP; a CML duration ' 12 months). Patients and methods. From April 2001 to April 2010, patients treated consecutively at the Peking University People's Hospital, Peking University Institute of Hematology were nonrandomly assigned to treatment with imatinib or allo-HSCT according to whether the patient had an HLA-matched sibling donor; those with an HLA-identical sibling donor were assigned to the allo-HSCT group, and the others were assigned to the imatinib group. QOL of surviving patients still in the imatinib and allo-HSCT groups was measured by the Medical Outcomes Survey Short Form 36 (MOS SF-36) at the end of the study evaluation period in April 2011. Results. In total, 463 patients were recruited, 209 patients were assigned to the allo-HSCT group and 254 patients were assigned to the imatinib group, respectively.Based on a ten-year follow-up period, a multivariate analysis revealed that allo-HSCT was an independent adverse prognostic factor for event-free survival (EFS; estimated HR=2.4, P=0.002 and estimated HR=0.31, P 〈 0.001) and overall survival (OS; estimated HR=6.9, P 〈 0.001 and estimated HR=26.2, P=0.001) for the total population (n=463) and the patients in the ECP (n=348), and an independent favorable predictor of progression-free survival (PFS; estimated HR=3.2, P=0.020) for the total population. Imatinib was superior to allo-HSCT, with six-year EFS and OS rates of 83.6% vs. 76.6% (P=0.041) and 96.4% vs. 82.0% (P 〈 0.001), respectively, for the entire cohort and 90.3% vs. 74.3% (P=0.001) and 99.4% vs. 80.2% (P 〈 0.001), respectively, for the patients in the ECP, despite six-year PFS rates of 90.7% vs. 96.6% (P=0.014), respectively, for the entire cohort and 95.9% vs. 97.3% (P=0.303) respectively, for the patients in the ECP. Both treatments resulted in similar EFS and OS rates in those in the LCP (n=115), with a probability of six-year EFS rate of approximately 80% and six-year OS rate of more than 90%. More LCP patients in the imatinib group experienced relapse compared with those in the allo-HSCT group, with six-year PFS rates of 86.0% vs. 100% (P=0.035), respectively. There was no correlation between the EBMT risk score and EFS, OS or PFS in the patients receiving allo-HSCT. Among the 392 surviving patients who were invited to participate in the QOL survey, 295 (75.3%) patients including 180 of 218 (82.6%) in the imatinib group and 115 of 174 (66.1%) in the allo-HSCT group, respectively, completed the questionnaires. A multivariate analysis revealed that there was no correlation between the treatment mode and the physical health for the total, ECP and LCP population, however, allo-HSCT was one of the independent factors associated with good mental health (estimated HR=0.5, P 〈 0.001) in the ECP patients. The Physical Component Summary were comparable between the imatinib group and the allo-HSCT group, however, the Mental Component Summary of the patients experienced allo-HSCT were better than those receiving imatinib for the total (P=0.001), ECP (P=0.015) and LCP (P=0.010) population. Conclusions. We concluded that imatinib confers significant survival advantages and a desirable QOL and is superior to allo-HSCT as the first-line therapy for patients with CML in the ECP. All trials were registered with www.chictr.org as CHiCHTR-TNC-10000955. Disclosure: No relevant conflicts of interest to declare. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
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  • 14
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1013-1013
    Abstract: Introduction Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with mortality over 80%. Effective management of TA-TMA is hampered by obscure pathogenesis and delayed diagnosis. There are no well-acknowledged therapeutic strategies for TA-TMA. TA-TMA-directed therapy includes therapeutic plasma exchange (TPE), eculizumab, rituximab, and defibrotide. The efficacy and outcome of TPE for the treatment of TA-TMA remain controversial. To our knowledge, this is the largest cohort to date of patients treated with TPE for TA-TMA after allo-HSCT. We aimed to identify predictors of response and mortality in patients with TA-TMA who received TPE, and to recognize patients who will benefit from TPE management. Methods A total of 6241 subjects who underwent allo-HSCT were performed at Peking University People's Hospital from January 2010 to December 2019, of whom 538 patients were diagnosed with TA-TMA, with a cumulative incidence of 8.6%. Among them, 82 consecutive critically ill TA-TMA patients received TPE. TA-TMA was diagnosed using the criteria proposed by Cho et al. TPE was not performed in a protocol-defined manner. Patients were classified as achieving complete response (CR) if they showed disappearance of schistocytes, resolution of any changes in mental status, normalization of lactic dehydrogenase, and were not receiving red blood cells and platelet transfusions. Patients were considered to have achieved no response (NR) when they showed no improvement of laboratory features, remained dependent on red blood cell and/or platelet transfusions, or died with active TA-TMA. Subjects were considered to have a partial response (PR) when they did not meet the criteria for either CR or NR (BMT 2010; Blood 2020). Results TA-TMA was diagnosed at a median time of 64.5 [IQR 38.8-158] days post-HSCT. The 42 men (51.2%) and 40 women (48.8%) had an average age of 35.3 years. Renal involvement (59.8%), central nervous system dysfunction (70.7%), gastrointestinal (GI) bleeding (73.2%), and concomitant acute graft-versus-host disease (aGVHD, 78%) were common in our cohort of TA-TMA patients. All 82 patients in our analysis received TPE, and adjunctive TA-TMA-targeted therapy included the use of rituximab (11 patients), rituximab plus eculizumab (1 patient), and defibrotide (1 patient). However, the additional therapy showed no significant difference between the response and nonresponse groups. The median time from TA-TMA to TPE initiation was 8 days [IQR 2.0-16.5], and the cumulative volume of TPE was 6 L [IQR 3.6-8.5] . Our data revealed that the overall response was 52.4% (43/82), comprising 4 CRs and 39 PRs. Early TPE initiation trended towards a better response, but this difference was not statistically significant. The multivariate analysis showed that patients with GI bleeding (OR, 6.26; 95% CI, 1.30-30.12), grade III-IV aGVHD (OR, 5.00; 95% CI, 1.50-16.68), lower cumulative volume of TPE (OR, 8.51; 95% CI, 1.91-38.05), and severe anemia (OR, 7.48; 95% CI, 2.20-25.49) were less likely to respond to TPE. Regarding treatment outcome, 57% (47/82) of cases survived 100 days post HSCT, and 20% (16/82) survived 100 days after the diagnosis of TA-TMA. With a median follow-up of 467 days [IQR 248-1002], the OS at 1 year after TA-TMA was 15%. The leading causes of death were infection, active TA-TMA, and multiple organ dysfunction syndrome (MODS). The Kaplan-Meier analysis showed that GI bleeding, grade III-IV aGVHD, and no response to TPE were associated with poor survival at 1-year post TA-TMA (Figure 1). By multivariate analysis, TA-TMA patients treated with TPE had dismal survival with GI bleeding, lower loading volume of TPE, and elevated total bilirubin. Conclusions The results of this large cohort of real-world practice indicate that TPE may be effective for TA-TMA depending on given clinical circumstances. Our data underscore that GI bleeding is independently associated with poor response to TPE and mortality, while grade III-IV aGVHD is again confirmed as predicting a dismal response to TPE. We hypothesize that higher volume of TPE is warranted to achieve resolution and favorable outcome of TA-TMA. Multicenter prospective studies are required to further verify whether these patients could benefit from TPE and seek a paradigm for TPE in the management of TA-TMA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 15
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 312-312
    Abstract: Introduction: Relapse remains the main cause of failure of hematopoietic stem cell transplantation (HSCT) in acute leukemia. NK cells have the property of killing leukemia cells without GVHD aggravation theoretically. Moreover, in some cases, leukemia cells may lost HLA-I and/HLA-II antigens which would result in poor response to the immunotherapy except NK-based adoptive effectors. Objective: In present study, the safety and efficacy of donor-derived ex-vivo activated NK cells in management of relapse after allogeneic HSCT in high-risk acute leukemia were examined. Patients and methods: Between July 2012 and July 2014, 29 patients with acute leukemia who received NK cell infusion after HSCT were analyzed retrospectively. Some cases failed to chemotherapy combined with donor lymphocyte infusion (DLI) before NK cell therapy. The diagnosis were ALL (10 cases), AML (18 cases) and mixed acute leukemia (1 case). All patients were high-risk leukemia. The disease status before transplant was CR1 in 8 cases, CR2 in 7, CR3 in 1 and non-remission in 13. The types of donor included identical sibling (5 cases), haploientical family member (21 cases) and unrelated donor (3 cases). The conditioning and GVHD prophylactic regimens were reported previously (Lu DP et al., Blood 2006; 107:3065). Minimal residual disease (MRD) was detected by either quantitative RT-PCR for fusion genes or flow cytometry or both. The expression of HLA-I and HLA-II antigens in leukemia cells was evaluated by flow cytometry. Donor-derived either peripheral blood stem cells or lymphocytes were cultured for 6 days using original culture system (AIM-V medium with IL-2, IL-12, IL-15 and IL-21) or modified culture system (SCGM medium with IL-2, IL-12, IL-15, IL-18 and IL-21). Escalated dosage of NK cells were infused starting with 1×105 cells/kg (recipient’s body weight) with or without IL-2 injection. Nine patients were in prevention group and 20 cases were in treatment group. The patients with hematologic relapse received NK cells 3 days later after chemotherapy. Results: Compared with our original culture system, the modified culture system enhanced approximately 10% to 20% of the purity and 4 to 8 fold in number of NK cells by day 6. Furthermore, our modified culture system elevated the expression of function phenotype including TRAIL, NKG2D and CD62L on NK cells in approximately 8 to 10 folds at day 6 and simultaneously stimulated higher level of IFN-γ. One to 4 NK cell infusions were given in each case with two week interval. Two of 29 cases developed mild skin GVHD. No transfusion-related side effects were noted. In prevention group, four of 9 cases remain complete remission, and the other 5 patients became MRD positive or relapse. In treatment group, seven of 20 cases have response to NK cell therapy, and two out of 7 cases who response to NK cells had failed to chemotherapy plus DLI before. Among 11 patients who had response to NK cells, eight of them are AML, and the remaining 3 patients are ALL. Higher response rate (10/23 cases) was seen with NK cell therapy by our modified culture system compared with the one (1/6 cases) by our original culture system. Conclusions: Our preliminary results have demonstrated that donor-derived ex-vivo activated NK cells are safe and effective modality in the management of relapse after allogeneic HSCT in high-risk acute leukemia even failed to chemotherapy combined with DLI. Optimal culture system has improved not only NK cell’s purity, number and function phenotype but also clinical efficacy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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    detail.hit.zdb_id: 80069-7
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  • 16
    In: Blood, American Society of Hematology, Vol. 125, No. 25 ( 2015-06-18), p. 3956-3962
    Abstract: Haploidentical transplant achieves outcomes similar to those of identical-sibling transplant for AML patients in first remission. Haploidentical transplant is a valid postremission treatment of intermediate- or high-risk AML patients lacking an identical donor.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 17
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3217-3217
    Abstract: Introduction: Cytogenetics is an independent prognostic factor in acute myeloid leukemia (AML). Molecular genetics including leukemia fusion gene, gene mutation and gene over expression are recognized to have significant impact on survival in patients with AML as well. In present study, the impact of cytogenetic and molecular markers on disease-free survival (DFS) of allogeneic hematopoietic stem cell transplantation (HSCT) for AML was investigated. Methods: Between April 2012 and December 2014, consecutive 345 patients with AML who underwent allogeneic HSCT in our center were analyzed retrospectively. All patients were either in poor-risk or in good-risk/intermediate-risk but with persistent minimal residual disease. The median age was 19 (1.8 to 64) years old. Children (≤14 years) were 96 (27.8%) cases and adults ( 〉 14 years) were 249 (72.2%) cases. Male to female was 200:145. The median disease course was 6 (1-64) months. Leukocyte count at diagnosis was 〈 30 x 109/L in 230 (66.7%) patients (low leukocyte) and ≥30 x 109/L in 115 (33.3%) cases (high leukocyte). Transplants at CR1, ≥CR2, and advanced disease were 168 (48.7%), 53 (15.4%) and 124 (35.9%), respectively. Donor sources were identical sibling (IS) in 45 (13.0%) cases, unrelated (UR) in 71 (20.6%) cases and haploidentical (HI) in 229 (66.4%) cases. Myeloablative conditioning regimens were administered with either Busulfan (Bu) plus Cyclophosphamide (Cy)/Fludarabine (Flu)-based in 285 (82.6%) patients or total body irradiation (TBI) plus Cy/Flu-based in 60 (17.4%) patients. Antithymocyte globulin was used in unrelated and haploidentical HSCT. Unmanipulated bone marrow and peripheral blood stem cells (PBSC) for IS and HI HSCT and PBSC for UR transplant were applied as the grafts. Cyclosporine, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Results: Univariate analysis showed that DFS after allogeneic HSCT in AML was not associated with patient age (children vs. adults, 70.3% vs. 69.4%, p=0.6), leukocyte count at diagnosis (low leukocyte vs. high leukocyte, 68.8% vs. 71.3%, p=0.8), donor source (IS vs. UD vs. HI, 77.3% vs. 76.8% vs. 65.8%, p=0.21), and conditioning regimen (Bu-based vs. TBI-based, 70.1% vs. 67.3%, p=0.45). Multivariate analysis indicated that disease status before HSCT was the only impact factor on DFS (CR1 vs. ≥CR2 vs. advanced disease, 81.6% vs. 70.0% vs. 53.1%, p 〈 0.0001). Therefore, total 221 of 345 patients with AML in complete remission pre-conditioning were analyzed for impact of cytogenetic and molecular markers on survival after HSCT. DFS rates were 79.1%, 80.4%, 74.1% in good-risk, intermediate-risk, poor-risk cytogenetics groups (p=0.81), respectively. According to gene mutations, the DFS rates were 100% in CEBPA+, 91.6% in IDH1+/NPM1+, 85.7% in Flt3-ITD+, 81.5% in c-KIT+, 75.0% in no mutation, 70.2% in MLL-PTD+/ASXL1+/TET2+, 54.3% in Flt3-ITD+ with other mutations (p=0.42). According to gene expression, the DFS rates were 100% in DEK-CAN+, 100% in HOX11+/EVI1+, 84.8% in no abnormal gene expression, 83.3% in CBFb-MYH11+, 78.5% in WT1+, 76.5% in MLL+, 74.9% in AML1-ETO+, 0% in TLS-ERG+ (p=0.004). Conclusions: Under our HSCT protocol, disease status before transplant for the patients with AML has significant impact on DFS but not patient age, leukocyte count at diagnosis, donor source and conditioning regimen. Allogeneic HSCT has attenuated the influence of cytogenetics on DFS in patients with AML. Our preliminary data have shown that patients with CEBPA+, IDH1+/NPM1+, DEK-CAN+, HOX11+/NPM1+ have favorable survival, but patients with both Flt3-ITD+ and other gene mutations or with TLS-ERG+ have poor survival after allogeneic HSCT in AML. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 18
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3224-3224
    Abstract: Introduction: With GIAC regimen, haploidentical blood and marrow transplantation (haplo-BMT) has achieved comparable outcomes with identical sibling transplant (Dao-Pei Lu et al., Blood 2006; 107:3065). Our previous study has shown that the third party cell co-infusion in haplo-BMT (GIAC-3 regimen) could significantly reduce aGVHD and transplant-related mortality (TRM). We have also demonstrated that individualized chemotherapy to decrease leukemia burden followed by conditioning could improve disease-free survival (DFS) in refractory/relapsed AML. Objective: To learn the outcomes of our haplo-BMT with these integrated approaches, all patients who received haplo-BMT for hematologic malignancies in our center were analyzed retrospectively. Methods: Between April 2012 and December 2014, consecutive 514 patients with hematologic malignancies who underwent haplo-BMT were included. The median age was 20 (1.8 to 64) years old. The diagnosis included AML 232 (45.1%), ALL 207 (40.3%), MDS 27(5.3%), CML 14 (2.7%), lymphoma 13 (2.5%) and others 21 (4.1%). Transplants at CR1, ≥CR2 or advanced disease were 216 (42.0%), 114 (22.2%), 184 (35.8%), respectively. All patients received unmanipulated bone marrow (BM) and peripheral blood stem cells as graft after myeloablative conditioning plus ATG. Majority of the patients with AML received BuCy-based conditioning, while most ALL patients received TBICy-based regimen. Fludarabine was substituted for cyclophosphamide in some patients due to impaired organ function or high tumor burden. For refractory/relapsed diseases, individualized chemotherapy followed by conditioning was administered. Cyclosporine/tacrolimus, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Either 1ml/kg (recipient's body weight) haploidentical BM from the second haploidentical donor or one unit of unrelated cord blood was infused right after haplo-BMT as the third party cells. Minimal residual disease (MRD) was monitored routinely by quantitative PCR or flow cytometry. The patients with persistent MRD were interfered by immunosuppressant withdrew, adoptive immunotherapy with cytokine induced killer or NK cells or donor lymphocyte infusion. Results: All patients but 5 achieved durable engraftment. The cumulative incidences of grade II to IV aGVHD and grade III to IV aGVHD were 32.2%, 19.8%, respectively. The cumulative incidences of cGVHD and extensive cGVHD were 48.3%, 18.4%, respectively. 100-day TRM and 2-year TRM were 4.1%, 14.9%, respectively. Two-year relapse rate was 22.8%. With the median follow up 17 (6 to 38) months, overall 2-year DFS rates in CR1, ≥CR2 and advanced disease were 75.6%, 70.9%, 49.2%, respectively. For AML, two-year DFS rates in CR1, ≥CR2 and advanced disease were 74.1%, 76.9%, 48.2% (CR1 vs. ≥CR2, p=0.84; CR vs. advanced disease, p=0.000). For ALL, two-year DFS rates in CR1, ≥CR2 and advanced disease were 78.9%, 56.6%, 38%, respectively (CR1 vs. ≥CR2, p=0.018; CR1 vs. NR, p=0.000; ≥CR2 vs. NR P=0.02 ). Conclusions: With our strategies, overall outcomes of haplo-BMT have been improved remarkably and very encouraging. Therefore, haplo-BMT should be an important way to save life for the patients with hematologic malignancies who need urgent BMT but without matched either sibling or unrelated donor. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
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  • 19
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3077-3077
    Abstract: Abstract 3077 Background: Since prolonged thrombocytopenia (PT) is an independent risk factor for poor clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the underlying mechanisms need to be understood in order to develop selective treatments. Previous studies1–4 have suggested that abnormalities in B cells may play a role in the pathogenesis of PT. However, abnormalities in B cells alone do not fully explain the complete pathogenic mechanisms of PT. Our previous studies5 showed that the frequency of megakaryocytes with a ploidy value ≤ 8N was significantly increased in patients who developed PT after allo-HSCT compared to the control group. Mechanisms concerning the megakaryocyte hypoplasia in PT after allo-HSCT are not well understood. Design and Methods: PT was defined as a platelet count ≤80 × 109/L for more than 3 months after HSCT, recovery of all other cell counts, and no apparent cause for thrombocytopenia, such as aGVHD, disease recurrence, CMV infection, or antiviral drug treatment at three months post-HSCT when all other blood cell counts had return to normal.5 We analyzed T cell subsets in bone marrow (BM) and peripheral blood (PB) from allo-HSCT recipients with and without PT (n = 23 and 17, respectively) and investigated the expression characteristics of homing receptors CX3CR1, CXCR4 and VLA-4 by flow cytometry. Futhermore, Mononuclear cells (MNCs) from PT patients and controls were cultured with and without autologous CD8+ T cells in vitro, and clarify the effect of activated CD8+ T cells on the ploidy and apoptosis of megakaryocytes in the bone marrow. Results: The results demonstrated that the percentage of CD3+ T cells in the BM was significantly higher in PT patients than the experimental controls (76.00 ± 13.04% and 57.49 ± 9.11%, respectively, P 〈 0.001), whereas this difference was not significant for the PB (71.01 ± 11.49% and 70.49 ± 12.89%, respectively, P = 0.911). While, some T cell subsets in the BM and PB from allo-HSCT recipients with PT were not significantly different from that of the experimental control group, such as CD8+ T cells, CD4+ T cells, CD4+ CD25bright T cells (regulatory T cells), CD44hi CD62Llo CD8+ T cells and naive T cells (CD11a+ CD45RA+). Furthermore, the surface expression of homing receptor CX3CR1 on BM T cells (64.16 ± 14.07% and 37.45 ± 19.66%, respectively, P 〈 0.001) and CD8+ T cells (56.25 ± 14.54% and 35.16 ± 20.81%, respectively, P = 0.036), but not in blood, were significantly increased in PT patients compared to controls. For these two groups of patients, the surface expression of CXCR4 and VLA-4 on T cells and CD8+ T cells from both BM and PB did not show significant differences. Through the study in vitro, we found that the activated CD8+ T cells in bone marrow of patients with PT might suppress apoptosis (MNC group and Co-culture group: 18.02 ± 3.60% and 13.39 ± 4.22%, P 〈 0.05, respectively) and Fas expression (MNC group and Co-culture group: 21.10 ± 3.93 and 15.10 ± 2.33, P 〈 0.05, respectively) of megakaryocyte. In addition, megakaryocyte with a ploidy value ≤ 8N (MNC group: 40.03 ± 6.42% and 24.54 ± 4.31%, respectively, P 〈 0.05) was significantly increased in patients with PT compared to the control group. Conclusions: In conclusion, an increased surface expression of CX3CR1 on T cells may mediate the recruitment of CD8+ T cells into the bone marrow in patients with PT who received an allo-HSCT. Moreover, CD8+CX3CR1+ T cells, which can have significantly increased numbers in bone marrow of patients with PT, likely caused a reduction in the megakaryocyte ploidy, and suppressed megakaryocyte apoptosis via CD8+ T cell-mediated cytotoxic effect, possibly leading to impaired platelet production. Therefore, treatment targeting CX3CR1 should be considered as a reasonable therapeutic strategy for PT following allo-HSCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 20
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2880-2880
    Abstract: The aim of this study is to investigate the prevalence and risk factors of anti-human leukocyte antigen (HLA) antibodies in haploidentical candidates. This study was completed at Peking University People's Hospital, Beijing China. We performed a prospective analysis of patients with hematological diseases concerning the prevalence and risk factors of anti-HLA antibodies. Patients were enrolled between July 2015 - December 2019. Serum was collected for PRAs test within 1 month before haploidentical transplantation. The risk factors, such as age, sex, total transfusion, red blood cell (RBC) transfusion, platelet (PLT) transfusion, pregnancy, disease duration and diagnosis were collected. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors of anti-HLA antibodies. Six hundred and eighty (17.9%) patients were positive for panel reactive antibodies (PRA)-class I, 360 (9.5%) for class II, 768 (20.2%) class I or II, and 272 (7.1%) positive for class I and II both. Multivariate analysis indicated that female was related to higher risk of having PRAs for class I (P = 0.011), class I or II (P = 0.009), anti-HLA-A (P = 0.015), anti-HLA-DP (P = 0.048) and also for having higher mean fluorescence intensity (MFI) (2000 or more) of PRAs in class I (P = 0.020) and class I or II (P = 0.005). Compared to patients with myelodysplastic syndrome (MDS), patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), aplastic anemia (AA) had a lower incidence for PRAs in class I, class II, class I or II, class I and II, anti-HLA-A. anti-HLA-B, anti-HLA-C, anti-HLA-DQ, anti-HLA-DR, anti-HLA-DP (Table 1). Prior pregnancy was a risk factor for PRAs (P & lt; 0.001), and no previous pregnancy group having lower MFI of PRAs in class I (P = 0.001) and class I or II (P = 0.004). PLT transfusion (more than 4 times) rleted with a higher prevalence of PRAs (P & lt; 0.001), and also had a higher MFI of PRAs in class II (P & lt; 0.001), class I and II (P & lt; 0.001). Patients with RBC transfusion (more than 3 times) had a higher prevalence of PRAs in class I (P = 0.001), class II (P = 0.029), class I or II (P & lt; 0.001), anti-HLA-A (P = 0.001), anti-HLA-B (P & lt; 0.001), anti-HLA-C (P = 0.007), anti-HLA-DQ (P & lt; 0.001) and anti-HLA-DR (P = 0.011). In addition, diseases duration (8 months or more) was also associated with higher MFI of PRAs in class I (P = 0.023) and class I or II (P = 0.004). Subgroup analysis showed that 11.7% of pediatric patients were positive for PRAs in class I; 19.2% of adults, 17.9% of elder patients; 12.4% of males; 26.1% of females; 21.0% of patients with AML; 10.5% of patients with acute lymphoblastic leukemia (ALL); 18.9% of patients with AA; 30.3% of patients with MDS; 16.6% of patients with other hematological diseases. The positive rate of class II PRAs in children was 4.3%; 11.1% for adults; 9.5% for elder patients; 5.5% for males; 15.4% for females; 11.4% for patients with AML; 5.2% for patients with ALL; 10.3% for patients with AA; 17.2% for patients with MDS; 6.6% of patients with other hematological diseases. Multivariate analysis showed that, in children, PLT transfusion and diagnosis were the two main risk factors of PRAs in class I and class II (P & lt; 0.001, P = 0.017). In adults, diagnosis (P = 0.003), transfusion (P & lt; 0.001) and pregnancy (P & lt; 0.001) were the three main factors associated with PRAs in class I and transfusion (P & lt; 0.001) and pregnancy (P & lt; 0.001) were the two main factors associated with PRAs in class II. In males, PLT transfusion (P & lt; 0.001) and diagnosis (P & lt; 0.001) were the two main factors associated with PRAs in class I and class II. In ALL subgroup, gender (P = 0.026, P = 0.048), pregnancy (P & lt; 0.001) and transfusion (P & lt; 0.001) were the three main factors associated with PRAs in class I and II. In AA subgroup, gender (P = 0.004) and PLT transfusion (P & lt; 0.001) were risk factors for class I PRAs, pregnancy (P = 0.008) and PLT transfusion (P = 0.003) were risk factors for class II PRAs. In elder patients, females, AML, MDS and other diseases subgroup, transfusion and pregnancy were the two main factors associated with PRAs in class I and class II. Our results indicated that female sex, diagnosis, pregnancy, transfusion, disease duration were independent risk factors of anti-HLA antibodies in haploidentical allograft candidates, which provided evidence for best haploidentical donor selection. The risk factors of anti-HLA antibodies were different among total patients and those of cases in different subgroups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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