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  • 1
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 871-871
    Abstract: Background: Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a devastating complication with limited therapeutic options. We aimed to assess the efficacy and safety of mesenchymal stem cells (MSCs) in BOS after allo-HSCT. Methods: Eighty-one allo-HSCT recipients with BOS diagnosed within 6 months were enrolled in this multicenter prospective cohort study. The choice of prednisone and azithromycin combined with or without MSCs was based on patient preferences (MSC n=49, non-MSC n=32). The primary endpoint was response rate at 3 months, defined as the proportion of patients achieving FEV1 improvement or steroid sparing. This trial was registered at ClinicalTrials.gov, NCT02543073. Results: Response rate was 35/49 patients (71%, 95% confidence intervals [CI] 59 to 84%) (FEV1 improvement n=10, steroid sparing n=25) and 14/32 (44%, 95% CI 27 to 61%) (FEV1 improvement n=3, steroid sparing n=11) in the MSC and non-MSC group, respectively (p=0.013). The adjusted odds ratio of response in the MSC group compared with the non-MSC group was 3.32 (95% CI 1.21-9.11; p=0.02). The addition of MSCs was associated with a better difference for change in FEV1 rate of decline, compared to non-MSC group (53 ml/months, 2 to 103; p=0.040). The 3-year overall survival post-diagnosis was 70.6% (95% CI 55.9 to 85.3%) and 58.2% (95% CI 36.1 to 78.5%) in the MSC and non-MSC group, respectively (p=0.21). Clinical improvement was accompanied by a significant increase of interleukin (IL)-10-producing CD5+ B cells. The incidences of infection and leukemia relapse were no significant difference between two groups. Multiple infusions of MSCs were well-tolerated with no serious adverse events. Interpretation: MSCs might be an effective and safe therapy for BOS patients after allo-HSCT. Our study strengthens evidence for clinical practice of MSC therapy in BOS. These data also offer insight into potential biological mechanisms of MSC treatment and support further investigation in larger randomized controlled trials. 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. 138, No. Supplement 1 ( 2021-11-05), p. 1793-1793
    Abstract: Background: Intestinal herpesvirus disease remains one of the major causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is lack of useful methods for etiological diagnosis of intestinal herpesvirus diseases. Here, we evaluated the efficiency of detecting herpesvirus in feces samples via real-time quantitative PCR (RQ-PCR) for diagnosis of intestinal herpesvirus diseases after allo-HSCT. Methods: This was a multicenter, prospective study. Patients with refractory diarrhea after intestinal graft-versus-host diseases (GVHD) were enrolled in this study. Laboratory tests which consisted of morphologic examination, immunohistochemistry, in situ hybridization, and RQ-PCR of tissue homogenate were used to detect viral pathogens including cytomegalovirus (CMV), epstein-Barr virus (EBV), herpes simplex virus (HSV)-I, HSV-II, varicella zoster virus (VZV), adenovirus (ADV) and human herpes virus (HHV)-6, HHV-7. These viruses aforementioned were also detected in feces and blood samples. Results: One hundred and seven patients with refractory diarrhea after intestinal GVHD were enrolled between January 2016 and December 2020. Based on the detection of viruses in biopsy specimens, 75 patients were diagnosed as intestinal infectious diseases including 64 accompanying with intestinal GVHD. CMV was the most frequent pathogen of intestinal infectious diseases (53.8%), followed by EBV (36.5%), bacteria (3.4%) and others (6.3%). For diagnosis of intestinal CMV diseases, the sensitivity and specificity of RQ-PCR in feces samples were better than those of blood (sensitivity: 96.9% v.s. 72.5%, p=0.004; specificity: 93.6% v.s. 75.8%, p=0.035). Similarly, the sensitivity of RQ-PCR in feces and blood samples were 88.2% and 21.9% (p & lt;0.001) and the specificity were 98.5% and 86.3% (p=0.032) for diagnosis of intestinal EBV diseases. Conclusion: Intestinal infectious diseases were one of the main causes of refractory diarrhea after intestinal GVHD. Herpesviruses, especially CMV and EBV, were the most common pathogens. Herpesvirus-DNA detection by RQ-PCR in feces samples was a useful diagnostic method for intestinal herpesviruses diseases. 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: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Preventive Medicine, Elsevier BV, ( 2023-11), p. 107785-
    Type of Medium: Online Resource
    ISSN: 0091-7435
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1471564-8
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  • 4
    In: British Journal of Haematology, Wiley, Vol. 204, No. 2 ( 2024-02), p. 628-637
    Abstract: This PASS‐ALL study was designed to explore the effect of paediatric‐inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high‐risk Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukaemia (HR PH‐ve B‐cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo‐HSCT). The PASS‐ALL study is a multicentre, observational cohort study, and 143 patients with HR B‐cell PH‐ve ALL were enrolled from five centres—77 patients allocated in the paediatric‐inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo‐HSCT. Three‐year leukaemia‐free survival (LFS) in the paediatric‐inspired cohort was 72.2% (95% CI 60.8%–83.6%) compared with 44.6% (95% CI 31.9%–57.3%; p = 0.001). Furthermore, time‐to‐positive minimal residual disease (TTP‐MRD) post‐HSCT was marked different, 3‐year cumulative incidence of relapse was 25.9% (95% CI 15.8%–37.2%) in paediatric cohort and 45.4% (95% CI 40.0%–57.9%) in adult cohort ( p = 0.026). Finally, the 3‐year OS rate was 75.3% (95% CI 64.9%–85.7%) for the paediatric‐inspired cohort and 64.1% (95% CI 51.8%–76.4%) for the adult cohort ( p = 0.074). On a multivariate analysis, paediatric‐inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327–4.862, p = 0.005). Collectively, our data suggest that paediatric‐inspired chemotherapy pre‐HSCT results in deeper and durable MRD response reduces relapse post‐HSCT and improves survival in HR B‐cell PH‐ve ALL patients with allo‐HSCT.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2024
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  • 5
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 260-260
    Abstract: INTRODUCTION Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR aGVHD. To assess efficacy and safety of MSCs combined with anti-CD25 antibody and calcineurin inhibitors as second-line therapy for SR aGVHD. METHORDS A randomized phase 3 trial involved 203 SR aGVHD patients at 10 centers in China (September 2014-March 2019). Final follow-up was on June 30, 2020. Participants were randomized in a 1:1 ratio to receive second-line therapy (anti-CD25 antibody combined with calcineurin inhibitors) with MSCs (n=101) or without MSCs (n=102). The primary endpoint was overall response (OR) at day 28 with a predefined threshold of -20%. Secondary and safety endpoints included durable OR at day 56, failure-free survival, overall survival (OS), chronic GVHD (cGVHD), infection, haematological toxicity and relapse. RESULTS Of 203 patients, 198 (97.5%; mean age, 30.1years; 40.4% women) completed the study. OR at day 28 was higher in the MSCs group than in the control group (82.8% [82 patients] vs 70.7% [70] ; odds ratio, 2.00; 95% confidence interval [CI], 1.01-3.94; P=.043). Durable OR at day 56 was also higher in the MSCs group (78.8% [78 patients] vs. 64.6% [64]; odds ratio, 2.02; 95% CI, 1.08-3.83; P=.027). The median failure-free survival was longer in the MSCs group compared with control group (11.3 months vs. 6.0 month; hazard ratio (HR) 0.68; 95% CI, 0.48-0.95, P=.024). The 2-year cumulative incidence of cGVHD was 39.5% (95% CI, 29.3%-49.4%) and 62.7% (51.4%-72.1%) in the MSCs and control groups (HR 0·55, 95% CI, 0·36-0·84; P=0·005). Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections (65 [65.7%] in the MSCs group vs 78 [78.8%] in the control group), haematological toxicity (37 [37.4%] vs 53 [53.5%]). CONCLLUSIONS MSCs plus second-line treatments may increase the efficacy of SR aGVHD, decrease drug toxicity of second-line therapy and cGVHD development, and are well tolerated. 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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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 2 ( 2023-01-10), p. 343-353
    Abstract: It remains controversial whether busulfan-based versus total body irradiation (TBI)–based regimens have comparable outcomes in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We investigated the efficacy and toxicity of busulfan plus cyclophosphamide (BuCy) and TBI plus cyclophosphamide (TBI-Cy) conditioning in allo-HSCT for adult standard-risk B-cell-ALL in first complete remission (CR1). PATIENTS AND METHODS We performed an open-label, randomized phase III trial at 13 hospitals in China. Eligible patients (age 14-65 years) had standard-risk ALL in CR1. Patients were randomly assigned (1:1) to BuCy (0.8 mg/kg four times per day on days –7 to –4 and cyclophosphamide 60 mg/kg once daily on days –3 to –2) or TBI-Cy (4.5 Gy TBI on days –5 to –4 and cyclophosphamide 60 mg/kg once daily on days –3 to –2). The primary end point was 2-year overall survival. Analysis was per protocol. This trial is registered with ClinicalTrials.gov (identifier: NCT02670252 ) and is complete. RESULTS Between January 2016 and February 2020, 275 patients were assigned to receive BuCy (273 assessed) and 275 to TBI-Cy (272 assessed). The 2-year overall survival was 76.6% (95% CI, 71.7 to 81.8) and 79.4% (74.7 to 84.4; P = .457; difference 2.9%; 95% CI, –4.1 to 9.8; P = .022), indicating noninferiority of BuCy. The 2-year relapse was 20.2% (95% CI, 15.6 to 25.1) and 18.4% (14.0 to 23.2; P = .616), and the nonrelapse mortality was 11.0% (95% CI, 7.6 to 15.0) and 11.0% (7.7 to 15.1; P = .988) in the BuCy and TBI-Cy groups, respectively. There were no differences in regimen-related toxicity, graft-versus-host disease, or late effects between the two groups. CONCLUSION The BuCy regimen has noninferior efficiency and safety as TBI-Cy (4.5 Gy × 2) for patients with adult standard-risk B cell-ALL in CR1 undergoing HLA-matched allo-HSCT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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