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  • 1
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4653-4653
    Abstract: BACKGROUD:Mesenchymal stem cells (MSCs) are known to exhibit immunomodulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (AA). OBJECTIVE: To explore the efficacy and safety of allo-HSCT by co-transplantation with MSCs in AA patients. METHODS: We conducted a multi-center retrospective study to comparing the incidence and severity of acute GvHD, transplant-related complication and overall survival (OS) of allo-HSCT with or without co-injection of MSCs in AA patients. A total of 119 consecutive severe AA patients (64 males/55 females) undergoing allo-HSCT at 4 hospitals from January 2012 to February 2018 were analyzed. The median age of the patients is 23 (range 1-56 years). Patients received conditioning regimens based on cyclophosphamide or busulfan, among whom 50 (42%) were MSD-HSCT, 21(17.6%) MUD-HSCT and 48 (40.4%) haplo-HSCT. All patients received cyclosporine A with short course methotrexate for prevention of GVHD. 89 patients transplanted with donor HSCs only, and 30 patients transplanted with HSCs and MSCs .MSCs infusion dose was 0.5-3.0×106/kg, at -1~+1 days following HSCs infusion. None of these patients had severe infection or organ failure before HSCT. RESULTS: The two groups were well matched demographically. All patients achieved successful engraftment within one month post transplant. There was no difference in time to leukocyte and platelet engraftment in the two groups. The incidence of aGVHD grade II-IV (7.9 % versus 6.7 %, P =1.000) was similar in the HSC versus MSC groups, but there was a trend to a lower incidence of aGVHD grade III-IV in the MSC group (3.4% versus 0%, P=1.0). Moreover, a lower incidence of viremia in the MSC group was observed (CMV: 26.7% vs 62.9%, P 〈 0.001; EBV: 50% vs 80.9%, P = 0.002).With a median follow-up time of 811 days (range:28-2348days),the 2-yr OS was similar in both groups (82.8% versus 71.1%, P =0.498). A combination of bone marrow and peripheral blood as the sources of stem cells co-transplanted with MSCs (n=9) demonstrated an improved survival benefit (2-yr OS=100%). CONCLUSION: Co-transplantation with MSCs could ameliorate the challenges of aGVHD and viremia and facilitate survival in allo-HSCT for AA patients. 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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  • 2
    In: The Journal of Clinical Pharmacology, Wiley, Vol. 62, No. 5 ( 2022-05), p. 609-619
    Abstract: Busulfan is a bifunctional alkylating agent that is widely used before hematopoietic stem cell transplantation (HSCT), in combination with other chemotherapeutic drugs. As of 2020, there is no population pharmacokinetic (popPK) model for busulfan in Chinese pediatric patients. A systemic external evaluation of 11 published popPK models was conducted in Chinese pediatric patients undergoing HSCT. Forty pediatric patients were enrolled in this study, with a total of 183 blood concentrations. The relative prediction error (PE%), median PE%, median absolute PE%, and percentage of PE% within ±20% and ±30% were calculated in prediction‐based diagnostics. Simulation‐based diagnostics were conducted through a prediction‐ and variability‐corrected visual predictive check and the normalized prediction distribution error. The relative individual prediction error was calculated using Bayesian forecasting with 1 to 3 concentration points. The 1‐compartment open linear popPK model, which was built by Su‐jin Rhee et al (model H), incorporating the patient's body surface area, age, dosing day, and aspartate aminotransferase as significant covariates had preferable predictability than other popPK models. In prediction‐based diagnostics, the median PE%, percentage of PE% within ±20%, and percentage of PE% within ±30% of model H were 8.48%, 45.35%, and 59.56%, respectively. The normalized prediction distribution error of model H showed that it followed the normal distribution. Based on Bayesian forecasting, model H showed good predictive performance. Thus, model H was the most appropriate model that can be used clinically for individualized dosage adjustments in Chinese pediatric HSCT patients.
    Type of Medium: Online Resource
    ISSN: 0091-2700 , 1552-4604
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2022
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    SSG: 15,3
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  • 3
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 58, No. 10 ( 2017-10-03), p. 2349-2355
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2030637-4
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  • 4
    Online Resource
    Online Resource
    Hindawi Limited ; 2015
    In:  Case Reports in Hematology Vol. 2015 ( 2015), p. 1-5
    In: Case Reports in Hematology, Hindawi Limited, Vol. 2015 ( 2015), p. 1-5
    Abstract: Ultra early posttransplantation lymphoproliferative disorder (PTLD) is a rare and fatal complication after hematopoietic stem cell transplantation (HSCT). Here we report, by lymph node (LN) flowcytometry, that we early recognized ultra early PTLD after an HLA-matched sibling allo-HSCT followed by a successful treatment with anti-CD20 antibody (rituximab) in a patient in progress disease for angioimmunoblastic T-cell lymphoma (AITL). The patient was conditioned with a reduced intensity conditioning (RIC) regimen. One week after transplantation, the patient developed high fever, generalized fatigue, high Epstein-Barr virus (EBV) load, and LN enlargement. An LN lymphocyte suspension and peripheral blood flowcytometry was performed to find majority of LN lymphocytes highly expressed CD20. By highly suspicious PTLD, 4 doses of rituximab (375 mg/m 2  qw) were given immediately followed by reducing and withdrawing immunosuppressant reagent. PTLD was later confirmed by pathology. The patient had good response to rituximab, showing absence of fever, reduction in LN size, and no detectable EBV-DNA. Twenty months after HSCT, the patient remains well without evidence of AITL and PTLD. The current report is one of the earliest cases of PTLD after HSCT. Taken together, by LN flowcytometry as a prompt recognition, rituximab can be an effective preemptive therapy for ultra early developed PTLD.
    Type of Medium: Online Resource
    ISSN: 2090-6560 , 2090-6579
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
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  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 4512-4513
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 4512-4513
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 6
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 38-38
    Abstract: BACKGROUND: There is currently no unified standard protocol for the prevention of hepatitis B virus (HBV) infection in patients with hematopoietic stem cell transplantation. The incidence of HBV infection is high in China, particularly in the Fujian Province of China. Nevertheless, there are also many transplanted patients who are not infected with HBV as indicated by serology markers (negative for HBsAg, anti-HBsAb, HBeAg, anti-HBeAb, anti-HBcAb, HBV-DNA). Therefore, there is a need to develop a protocol to prevent hepatitis virus infection in these non-infected patients. AIMS: This study aims to determine the changes in HBV immune status after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients not infected with HBV for establishing a management protocol to prevent HBV infection in these patients after allo-HSCT. METHODS: The study included 54 patients in non-B hepatitis virus-infected who received allo-HSCT at the Fujian Medical University Union Hospital between March 2013 and April 2020 for acute myeloid leukemia (n=22), acute lymphoblastic leukemia (n=18), chronic myeloid leukemia (n=3), aplastic anemia (n=5), lymphoma (n=2) and myelodysplastic syndrome (n=4). All patients were tested for hepatitis B serum markers by ELISA and HBV-DNA by PCR before and every 2 weeks after transplantation but did not receive hepatitis B immunoglobulin to prevent HBV infection. Four patients received Entecavir prophylactic antiviral therapy because the stem cells came from HBsAg positive donors (2 HBV-DNA negative, 2 HBV-DNA positive). Of the 50 HBsAg negative donors, 15 were anti-HBsAb negative, including 8 anti-HBcAb positive and 7 anti-HBcAb negative, and 35 were anti-HBsAb positive, of which 23 were anti-HBcAb positive and 12 anti-HBcAb negative. RESULTS: All 54 patients had changes in HBV immune status after allo-HSCT, including 48 cases positive for anti-HBsAb/anti-HBcAb (87.03%) and 7 cases positive for anti-HBsAb and negative for anti-HBcAb (12.96%). It means that all of these patients obtained protective antibodies against HBV. The median time (range) for HBV immune status changes was 5 (1-84) days after transplantation. The titer of HBsAb changed with immune reconstruction after transplantation. The median titers (mIU/ml) of HBsAb at Day 30, 60, 90, 120, 180 and 240 after transplantation were 258.49, 133.4, 33.17, 15.95, 26.89, and 27.99, respectively. On Day 30, 60, 90, 120, 180 and 240 post-transplantation, 18.91% (7/37), 41.17% (14/34), 50% (14/28), 72.2%, (13/18) of the anti-HBsAb and anti-HBcAb positive patients became negative. It means that these patients lost HbsAb but no new hepatitis B virus infection occurred during the median (range) follow-up of 299 (22-2572) days. CONCLUSIONS: After allo-HSCT, HBV-negative patients acquired HB surface antibodies, and the HBsAb titer gradually decreased to eventually disappear at the end of follow-up. Therefore, we do not recommend prophylactic anti-hepatitis B virus therapy in the early stage of hematopoietic stem cell transplantation in non-HBV infected patients. 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: 2020
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  • 7
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4542-4542
    Abstract: Objective: Several microRNAs have been revealed to be involved in the pathophysiological process of GVHD. This study aimed to characterize the functional relevance of epidermal growth factor (EGF)-stimulated microRNA-21 (miR-21) in the bone marrow-derived mesenchymal stem cells (BMSCs) in a mouse model of aGVHD. Methods: BMSCs and regulatory T cells (Tregs) were isolated and cultured. The effects of miR-21 knockdown or overexpression and EGF on cell activities of BMSCs as well as the expression of PTEN, Foxp3, AKT phosphorylation and extent of c-jun phosphorylation were examined by gain- and loss-of-function approaches. The efficacy and safety of EGF were further assessed in the mouse model of aGVHD. Results: Overexpression of miR-21 promoted the proliferation, invasion and migration of BMSCs. Besides, miR-21 in BMSCs-derived exosomes inhibited the expression of PTEN, enhanced AKT as well as GSK-3β phosphorylation and Foxp3 expression in Tregs. In addition, EGF enhanced c-jun phosphorylation to elevate the miR-21 expression. Furthermore, EGF significantly increased the effect of BMSCs in the mouse model of aGVHD, corresponding to reduced IFN-γ expression and organ damage. Moreover, the Foxp3 expression of Tregs in BMSCs-treated aGVHD mice was promoted by the treatment of EGF. Conclusion: Taken together, EGF induced the BMSCs-derived exosomal miR-21 expression to enhance the expression of Foxp3 in Tregs, thereby improving the therapeutic effect of BMSCs on aGVHD. 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
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3703-3703
    Abstract: High procalcitonin (PCT) levels are strongly associated with systemic bacterial infections. PCT is produced in response to bacterial endotoxin and inflammatory cytokines. Few studies are available in the literature on PCT ability to distinguish different strains of bloodstream infections in patients with hematologic diseases. The aim of the present study was to explore the value of determining serum PCT values early, i.e., as soon as blood cultures are positive, in a large population of patients with hematologic diseases. Patients with hematologic diseases admitted to the hematology department of our hospitalfrom January 2013 to March 2016 who had bloodstream infections were retrospectively analyzed. Patients whose blood samples were collected for simultaneous blood culture and PCT test were enrolled in the study, and they were divided into agranulocytosis and non-agranulocytosis groups. Automatic microbial analyzer was used to identify all strains, and PCT levels were analyzed with an automatic electrochemiluminescence system. The relationship between PCT levels and the strains in bloodstream infections was analyzed and compared, and the diagnostic efficacy of PCT was evaluated using the receiver operating characteristic (ROC) curve. A total of 494 bloodstream infection cases that fulfilled the inclusion criteria were included in the study, involving 312 cases of bloodstream infection with single Gram-negative, 146 cases with single Gram-positive, 12 cases with single fungi, 19 cases with polymicrobes, and 5 cases identified as contaminated specimens. Unpaired t-test was used for data analysis. PCT levels for single Gram-negative infection (15.17±2.11 ng/ml) were significantly higher than those for Gram-positive infection (3.30 ± 0.93 ng/ml) (P 〈 0.0001), or those for single fungi infection (0.22 ± 0.04 ng/ml) (P 〈 0.0001). PCT levels for single Gram-positive infection were also significantly higher than those in single fungi infection (P 〈 0.01). In the agranulocytosis group, which included 403 cases, the PCT levels in the single Gram-negative infection (14.14 ± 2.13 ng/ml) were significantly higher than those in single Gram-positive (2.49 ± 0.73 ng/ml) (P 〈 0.0001), or in single fungi infection (0.24 ± 0.04 ng/ml) (P 〈 0.0001). The PCT levels in the single Gram-positive bacterial infection were also significantly higher than those in single fungi infection (P 〈 0.01). In the single Gram-negative bacteria bloodstream infection, we further found that the PCT levels in Enterobacteriaceae infection (17.00 ± 3.04 ng/ml) were significantly higher than those in nonfermentative Gram-negatives infection (6.49 ± 1.50 ng/ml) (P 〈 0.01). ROC analysis was performed on monomicrobial blood cultures. ROC of single Gram-negative and Gram-positive infections revealed that the area under the curve (AUC) was 0.687, the best cut-off value was 0.58 ng/ml, the sensitivity was 60.81% and specificity was 71%. ROC of single Gram-negative and fungi infections revealed that the AUC was 0.795, the best cut-off value was 0.42 ng/ml, the sensitivity was 67% and specificity was 100%. ROC of single Gram-positive and fungi infections revealed that the AUC was 0.6, the best cut-off value was 0.44 ng/ml, the sensitivity was 37% and specificity was 100%. In the non-agranulocytosis group, we only found that the PCT levels in the single Gram-negative infection were significantly higher than those in single Gram-positive infection (P 〈 0.05). In summary, early serum PCT quantitative determination can be used as a routine test to help to distinguish Gram-negative bacteria, Gram-positive bacteria, or fungi bloodstream infections in patients with hematologic diseases. These findings will be of great clinical value to select appropriate antibiotics for patients with hematologic diseases and bloodstream infections. Figure Figure. 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
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  • 9
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5753-5753
    Abstract: OBJECTIVE: Relapse after autologous hematopoietic stem cell transplantation (ASCT) is still challenging for high-risk aggressive lymphoma. This study was to investigate the efficacy and safety of maintenance therapy post-ASCT. METHODS: From June 2009 to March 2018, patients with high-risk aggressive lymphoma in our hospital were treated with maintenance therapy post-ASCT according to the patient's wishes, and then assigned to maintenance group or observation group. The end point of follow-up was disease progression or death. The 3-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups. RESULTS: A total of 79 patients were enrolled, with a median age of 38 years (8-64 years), 50 males and 29 females. IPI score ≥2 points in 28 cases, stage III-IV in 58 cases, B symptoms in 21 cases, Extranodal lesions ≥ 2 in 17 cases, bone marrow infiltration in 15 cases, and 24 cases with partial remission (PR) prior to ASCT. In addition to 2 cases of early death, the remaining 77 patients with lymphoma were underwent successfully transplantation and achieved CR post-ASCT. 54 patients were assigned to the observation group, and 23 patients to the maintenance group, including 17 with rituximab and 6 with DPP/DCEP-G alternation regimen. There were no s ignificant differences in gender, age, pre-transplant disease status, and hematopoietic reconstitution between the two groups. The main causes of death were disease recurrence. No serious adverse reactions occurred during the maintenance treatment period. After a median follow-up of 616 days (12-2854 days), the relapse rates of the observation group and the maintenance group were 49.1% vs 12.9%, and the DFS of the 1st, 2nd, and 3rd years were 62.8% VS 93.8%, 48.1% VS 87.1%, and 45.3% VS 87.1% (P = 0.007), respectively. The OS of the 1st, 2nd, and 3rd years were 89.3% VS 100%, 83.2% VS 92.9%, and 76.2% VS 92.9% (P=0.212), respectively. Conclusion: Maintenance therapy post-ASCT could reduce the risk of relapse and promote disease-free survival, which deserves further investigation. 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
    detail.hit.zdb_id: 1468538-3
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  • 10
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2904-2904
    Abstract: Objectives: Natural killer (NK) cells are the first donor-derived lymphocytes to be reconstituted after transplantation and play a critical role in improving transplantation outcomes. Their surface receptor, killer cell immunoglobulin like receptor (KIR), can trigger the alloreactivity of NK cells and have been shown to be protective for acute and chronic graft-versus-host disease (aGVHD, cGVHD) while retaining graft-versus-leukemia (GVL) effect. However, different results have been reported about KIR matching models and KIR alleles based on patient, donor and transplant characteristics, resulting in significant controversy about the best donor selection strategy. Here, we investigated the potential influence of KIR matching and KIR alleles on GVHD prophylaxis, overall survival (OS) and relapse rate (RR) of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in acute myeloid leukemia (AML) patients. Methods:Data from 79 patients with AML treated with haplo-HSCT between May 2015 and May 2021 in the transplantation unit of the Fujian Medical University Union Hospital were retrospectively analyzed. The cohort included 49 male patients (62.0%) and 30 female (38.0%), with a median age of 25 years (1-68 years). KIR genotyping was performed by the PCR-SSO method. The amplicons were quantified on the Luminex 200 flow analyzer and analyzed using the Quick-Type for Lifecodes software for generating KIR data. HLA-A and -B alleles were typed by polymerase chain reaction using sequence-specific primers (PCR-SSP) (TBG, Taipei, Taiwan). HLA-C genotyping was determined by reverse hybridization with sequence specific oligonucleotides probes (rSSO) Line probe assay. Cox proportional hazards model and Kaplan-Meier survival curves were used for analysis. Results:At the time of transplantation, 49 cases (62.0%) were at CR1, while 30 (38.0%) were not. aGVHD occurred in 16 patients (20.3%) and recurrence arose in 10 patients (12.7%), 4 (5.1%) cases cGVHD was observed. After adjusting for age, disease-risk, disease-status, HLA-match, donor gender, conditioning regimen intensity and type of post-grafting GVHD prophylaxis, Cox regression analysis revealed that both KIR ligand-ligand mismatching (KLM) and KIR receptor-ligand matching (RLM) was associated with an decreased risk of aGVHD and relapse compared to KIR ligand-ligand matching and receptor-ligand matching group, respectively (aGVHD: KLM: p=0.047, RLM: p<0.001; RR: KLM: p=0.049, RLM: p=0.017). Furthermore, RLM shows more accurate in prediction of relapse and aGVHD compared with KLM in both aGVHD and relapse. (aGHVD: p=0.009; RR: p=0.039). After taking activating KIR (aKIR) into consideration to compensate the defect of only inhibitory KIR (iKIR) dominant model, we found that patients with more donor activating KIRs can reach the lower incidence of aGVHD and relapse, and the benefit can gradually increase parallel with the increase in donor activating KIRs. (aGVHD:p=0.019;RR:p=0.037). Patients with both receptor-ligand mismatch and the most donor aKIRs can reach the lowest relapse, lowest incidence of aGVHD and best overall survival (OS). Conclusions: KIR-mismatch, both KLM and RLM significantly reduced the risk of aGVHD and relapse after halpo-HSCT in AML patients and RLM show more superiority in the prediction of HSCT outcome. The synergistic effects of receptor-ligand mismatch and more donor aKIRs can provide a better clinically applicable donor selection strategy to improve haplo-HSCT outcome in AML patients. Disclosures Hu: Astellas Pharma, Inc.: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    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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