21,173 results on '"GRAFT versus host disease"'
Search Results
2. Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant
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- 2024
3. Chronic Graft-versus-Host Disease in the Oral Cavity of Patients Following Allogeneic Hematopoietic Stem Cell Transplant and Including Healthy Controls
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- 2024
4. Ruxolitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation
- Author
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Incyte Corporation
- Published
- 2024
5. A Study of Itolizumab in Combination With Corticosteroids for the First-Line Treatment of Acute Graft Versus Host Disease (EQUATOR)
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Biocon Limited
- Published
- 2024
6. CINC424A2X01B Rollover Protocol
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- 2024
7. Acute GVHD Suppression Using Costimulation Blockade to Expand Non-malignant Transplant (ASCENT)
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Thrasher Research Fund, Sickle Cell Transplant Advocacy & Research Alliance (STAR), Aflac Cancer and Blood Disorders Center, Bristol-Myers Squibb, and John T. Horan, MD, MPH, Associate Professor
- Published
- 2024
8. Relationship Between "FODMAPs" and "GVHD"
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Qi Xiao-Fei, Dean
- Published
- 2024
9. Study Testing Two Conditioning Regimen With a Single Prophylaxis of GVHD by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation (CY-MET-RIC)
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- 2024
10. Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders
- Author
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National Cancer Institute (NCI)
- Published
- 2024
11. A Difficult Case of Calcineurin Inhibitor Neurotoxicity Post-Haploidentical HCT With a Successful Novel Solution: Cytotoxic T-Lymphocyte-Associated Protein 4-Immunoglobulin Blockade for GVHD Prophylaxis.
- Author
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Dykes, Kaitlyn, Tzachanis, Dimitrios, and Koura, Divya
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T cells ,bone marrow ,cancer ,graft versus host disease ,oncology ,Humans ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Calcineurin Inhibitors ,Abatacept ,Male ,Middle Aged ,Immunosuppressive Agents ,Adult ,Female - Abstract
Post-allogeneic hematopoietic cell transplant (HCT) immunosuppression regimens are given as graft-versus-host disease (GVHD) prophylaxis. Most GVHD prophylaxis regimens are based on calcineurin inhibitors (CNIs). Unfortunately, CNIs are associated with significant associated morbidity, frequently cannot be tolerated, and often need to be discontinued. There is no consensus as to which alternative immunosuppression should be used in cases where CNIs have to be permanently discontinued. Cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocking agents are well tolerated and have been used extensively in patients with autoimmune disease and as post-transplant immunosuppression. There are two CTLA4-Ig agents: belatacept and abatacept. Belatacept is routinely used in adult kidney transplantation to prevent rejection and abatacept has been approved by the Food and Drug Administration (FDA) for GVHD prophylaxis in patients undergoing a matched or one allele-mismatched unrelated allogenic HCT. Herein, we describe a case in which abatacept was given off-label to replace tacrolimus GVHD prophylaxis in a patient with neurotoxicity undergoing haploidentical HCT. This case suggests that CTLA4-Ig blockade may be a good alternative to a CNI in cases where the CNI needs to be discontinued and warrants further investigation.
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- 2024
12. Sequential Administration of WJ-MSCs for the Treatment of GvHD Refractory to Second Line Treatment (GvHD)
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Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud - IDCBIS and Martha Ligia Arango Rodríguez, Scientific technical director of the Center for advanced therapies Fundación Oftalmológica de Santander (FOSCAL)
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- 2024
13. Optimizing PTCy Dose and Timing
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National Institute of Neurological Disorders and Stroke (NINDS)
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- 2024
14. A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan
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National Cancer Institute (NCI)
- Published
- 2024
15. The Skin Microbiome in Graft Versus Host Disease
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Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel
- Published
- 2024
16. Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002)
- Author
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Ohio State University, University of Michigan Rogel Cancer Center, Indiana University School of Medicine, Barbara Ann Karmanos Cancer Institute, and National Cancer Institute (NCI)
- Published
- 2024
17. Correlation of Serum Gasdermin-D and NLRP-3 Inflammasome Levels With GVHD Biomarkers and Endothelial Damage Markers in Graft-Versus-Host Disease
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Ugur Arzu Kulu, Research Assistant
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- 2024
18. High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant
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National Cancer Institute (NCI)
- Published
- 2024
19. PTCY Plus uhCG/EGF for Graft Versus Host Disease Prophylaxis
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Shatha Farhan, Clinical Assistant Professor
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- 2024
20. Identification of predictive models including polymorphisms in cytokines genes and clinical variables associated with post-transplant complications after identical HLA-allogeneic stem cell transplantation.
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Muñiz, Paula, Martínez-García, María, Bailén, Rebeca, Chicano, María, Oarbeascoa, Gillen, Carlos Triviño, Juan, de la Iglesia-San Sebastian, Ismael, Fernández de Córdoba, Sara, Anguita, Javier, Mi Kwon, Luis Díez-Martín, Jose', Olmos, Pablo M., Martínez-Laperche, Carolina, and Buño, Ismael
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STEM cell transplantation ,GENETIC polymorphisms ,HEMATOPOIETIC stem cell transplantation ,GRAFT versus host disease ,PREDICTION models ,OVERALL survival ,HEMATOLOGIC malignancies - Abstract
Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in noncoding regions. All models had a statistical significance of p<0.0001. Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients. [ABSTRACT FROM AUTHOR]
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- 2024
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21. ATG-Thymoglobulin Versus ATG-Fresenius for Conditioning in Thalassemia Patients Who Underwent Allogenic Stem Cell Transplantation from Matched-Sibling Donor: A Tertiary Cancer Care Center Short-Term Experience.
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Singh, Reema, Halder, Rohan, Hemant Gupta, Vinayak, Rainchwar, Sujay, Bhatia, Niharika, Mishra, Varsha, Panda, Tribikram, Patra, Pritish Chandra, Agrawal, Narendra, and Bhurani, Dinesh
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HEMATOPOIETIC stem cell transplantation , *STEM cell transplantation , *ANTIBODY specificity , *GRAFT versus host disease , *GRAFT rejection - Abstract
AbstractGraft rejection and Graft-versus-host disease (GVHD) are some of the significant factors resulting in morbidity and mortality following allogeneic hematopoietic cell transplantation. Prophylaxis for GVHD using T-cell depleting agents is helpful in reducing the transplant-related mortality and graft rejection. Both tATG and fATG exhibit varied amounts of antibody specificities and perform distinct immunomodulatory effects, regardless of their capacity to deplete T-lymphocytes. We conducted this single-center, retrospective study at our center to compare both formulations. Twenty-six patients were included in the study, 13 in each cohort. The median age at diagnosis of β-thalassemia was 5 months (range, 3–12 months) in the tATG group and 6 months (range, 3–9 months) in the f-ATG group, respectively. Acute GVHD was observed in 1 (7.7) and 2(15.4) in the tATG and fATG group, respectively. No cases of chronic GVHD were observed in either group. There was no difference in the mixed chimerism observed at 6 months in both groups, tATG (
n = 5, 38.5%) and fATG (n = 6, 46.15). There was 1 (7.6) rejection at day +72 observed in the tATG group, whereas no rejection was observed in the fATG group. At a mean follow-up duration of 288 days since transplant, there were no deaths in either of the groups. In conclusion, both ATG preparations showed equivalent effectiveness in preventing rejections and GVHD. However, further larger studies are required to establish the long-term efficacy and safety of both formulations in ASCT. [ABSTRACT FROM AUTHOR]- Published
- 2024
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22. Recent updates on allogeneic CAR-T cells in hematological malignancies.
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Mansoori, Shafieeh, Noei, Ahmad, Maali, Amirhosein, Seyed-Motahari, Seyedeh Sheila, and Sharifzadeh, Zahra
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HEMATOLOGIC malignancies , *GRAFT versus host disease , *GENOME editing , *T cells , *CELLULAR therapy - Abstract
CAR-T cell therapy is known as an effective therapy in patients with hematological malignancies. Since 2017, several autologous CAR-T cell (auto-CAR-T) drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of some kinds of relapsed/refractory hematological malignancies. However, some patients fail to respond to these drugs due to high manufacturing time, batch-to-batch variation, poor quality and insufficient quantity of primary T cells, and their insufficient expansion and function. CAR-T cells prepared from allogeneic sources (allo-CAR-Ts) can be an alternative option to overcome these obstacles. Recently, several allo-CAR-Ts have entered into the early clinical trials. Despite their promising preclinical and clinical results, there are two main barriers, including graft-versus-host disease (GvHD) and allo-rejection that may decline the safety and efficacy of allo-CAR-Ts in the clinic. The successful development of these products depends on the starter cell source, the gene editing method, and the ability to escape immune rejection and prevent GvHD. Here, we summarize the gene editing technologies and the potential of various cell sources for developing allo-CAR-Ts and highlight their advantages for the treatment of hematological malignancies. We also describe preclinical and clinical data focusing on allo-CAR-T therapy in blood malignancies and discuss challenges and future perspectives of allo-CAR-Ts for therapeutic applications. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Human leukocyte antigen evolutionary divergence as a novel risk factor for donor selection in acute lymphoblastic leukemia patients undergoing haploidentical hematopoietic stem cell transplantation.
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Xing-Yu Cao, Hai-Fei Zhou, Xiang-Jun Liu, and Xiao-Bo Li
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HLA histocompatibility antigens ,PROGRESSION-free survival ,HEMATOPOIETIC stem cell transplantation ,LYMPHOBLASTIC leukemia ,HUMAN stem cells ,GRAFT versus host disease - Abstract
Introduction: The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. Methods: In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptidebinding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. Results: The class I HED for recipient (R_HED
class I) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease. The patients with high class II HED for donor-recipient (D/R_HEDclass II) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HEDclass II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HEDclass II was an independent risk factor for the development of severe a GVHD (P = 0.007), and a high R_HEDclass I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. Discussion: While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD. In haploidentical setting, class II HED for donor-recipient pair (D/R_HEDclass II) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts. [ABSTRACT FROM AUTHOR]- Published
- 2024
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24. Immune recovery and the role of recent thymic emigrated T lymphocytes after pediatric hematopoietic stem cell transplantation.
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Justus, Julie Lillian Pimentel, Beltrame, Miriam P., de Azambuja, Ana Paula, Schluga, Yara C., Martins, Edna A., Rocha, Maria Tadeu Lemes, Rodrigues, Adriana Mello, Loth, Gisele, Lima, Alberto Cardoso Martins, and Bonfim, Carmem
- Subjects
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HEMATOPOIETIC stem cell transplantation , *CHILD patients , *OLDER patients , *GRAFT versus host disease , *OVERALL survival - Abstract
Adequate re-establishment of thymopoiesis is critical for long-term immune reconstitution after hematopoietic cell transplantation (HCT), potentially impacting patient survival rates. This study aimed to evaluate immune reconstitution in pediatric HCT recipients by quantifying recent thymic emigrants (RTEs), specifically CD3+CD31+CD45RA+ cells. We conducted a retrospective analysis of 186 pediatric patients transplanted between 2013 and 2020, undergoing their first allogeneic HCT, who were alive in the first 100 days after transplantation with immune recovery evaluation at three time points: day 100, day 180 and day 360 after HCT. We analyzed the distribution of peripheral blood subsets of T, B and natural killer lymphocytes and assessed the impact of underlying disease, HCT type, stem cell source, recipient age, conditioning regimen, graft-versus-host disease (GVHD) occurrence and cytomegalovirus (CMV) reactivation on immune recovery. At day 100, patients under 10 years exhibited higher RTE CD4+ and CD8+CD31+CD45RA+ counts compared with older patients (5.3 versus 2.2 cells/µL, P = 0.022 and 48 versus 72.8 cells/µL, P = 0.049, respectively). Patients with haploidentical HCT had lower RTE CD4+ counts compared with those with unrelated or related donors (2.4 versus 4.4 versus 7.9 cells/µL, P = 0.024). Administration of rabbit anti-thymocyte globulin negatively impacted RTE CD4+ production (median, 6.5 versus 2.4 cells/µL, P = 0.007). At day 180, the presence of GVHD had a negative influence on RTE production (11.7 versus 56.8 cells/µL, P < 0.001), particularly higher-grade acute GVHD (without, 56.8 cells/µL, grade 1–2, 28.1 cells/µL, grade 3–4, 6.0 cells/µL, P < 0.001). Patients with CMV reactivation had higher CD8+CD31+CD45RA+ compared with those without reactivation (median, 204.6 versus 100.2 cells/µL, P = 0.022). At day 360, no variables significantly affected RTE recovery. Overall survival at 5-year follow-up was 87.7%, with a median of 1170 days (range, 122–3316). Multivariate analysis showed that age >10 years (P = 0.038), negative CMV donor serology (P = 0.0029) and acute GVHD (P = 0.0026) had a negative impact on survival. This study highlights variations in RTE production based on patient age, donor type and immunosuppression regimen employed. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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25. Low-dose anti-thymocyte globulin plus low-dose posttransplant cyclophosphamide-based regimen for prevention of graft-versus-host disease in haploidentical peripheral blood stem cell transplantation for pediatric patients with hematologic malignancies.
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Du, Yanlu, Zhang, Ying, Xu, Xiaowei, Cai, Yu, Wei, Yu, Huang, Chongmei, Yang, Jun, Qiu, Huiying, Niu, Jiahua, Zhou, Kun, Xia, Xinxin, Shen, Chang, Tong, Yin, Dong, Baoxia, Wan, Liping, and Song, Xianmin
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STEM cell transplantation , *CHILD patients , *GRAFT versus host disease , *BLOOD cells , *EPSTEIN-Barr virus - Abstract
The low-dose anti-thymocyte globulin (ATG) plus low-dose post transplantation cyclophosphamide (PTCy) -based (low-dose ATG/PTCy-based) regimen had a promising activity in preventing of graft-versus-host disease (GVHD) in adult patients. However, its efficacy in pediatric patients remain to be defined. Here, we presented the findings from 35 pediatric patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with the new regimen for GVHD prophylaxis. The cumulative incidences (CIs) of grades II-III and III-IV acute GVHD (aGVHD) were 34% (95% CI, 17–48%) and 11% (95% CI, 0–21%) within 180 days post-transplantation, respectively. The CIs of chronic GVHD (cGVHD) and moderate-to-severe cGVHD within 2 years were 26% (95% CI, 7–41%) and 12% (95% CI, 0–25%), respectively. The 2-year probabilities of overall survival, relapse-free survival, and graft-versus-host disease and relapse-free survival were 89% (95% CI, 78–100%), 82% (95% CI, 68–98%) and 59% (95% CI, 43–80%), respectively. The CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation by day 180 were 37% (95% CI, 19–51%) and 20% (95% CI, 6–32%) respectively. These results strongly advocate for the efficacy of the low-dose ATG/PTCy-based regimen as a robust strategy for GVHD prevention in haplo-PBSCT for pediatric patients. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Efficacy and safety of ruxolitinib in the treatment of chronic graft-versus-host disease: a retrospective analysis.
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Denk, Alexander, Mittermaier, Cornelia, Weber, Daniela, Fante, Matthias, Güneş, Sibel, Edinger, Matthias, Herr, Wolfgang, and Wolff, Daniel
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GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *RUXOLITINIB , *PATIENTS' attitudes , *DRUG approval - Abstract
Steroid-refractory chronic graft-versus-host disease (cGvHD) is associated with significant morbidity and mortality, with ruxolitinib being the first drug approved for its treatment. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of cGvHD at our center between 07/2015 and 12/2022 and identified 48 patients receiving ruxolitinib as second (18/48) or advanced (30/48) treatment line. Ruxolitinib was started on median day 340 (range 119–595) after cGvHD onset; median duration of administration was 176 (range, 79–294) days with 16/48 patients continuing treatment at last follow-up. National Institutes of Health organ grading and the intensity of immunosuppression were assessed at the start of ruxolitinib treatment and repeated after 1, 3, 6, and 12 months. Response assessment was terminated at the start of any additional new immunosuppressant treatment. The median time of follow-up was 582 (range, 104–1161) days. At the primary analysis after six months on ruxolitinib treatment, the overall response rate was 33%, and failure-free survival was 58%. Infectious adverse events ≥ CTCAE grade III were observed in 10/48 patients. The response rate was not associated with the severity of cGvHD, number of previous treatment lines, or number of additional agents combined with ruxolitinib applying a univariate regression model. At the time of the 12-month follow-up, four patients experienced recurrence of the underlying malignancy and two patients had experienced non-relapse-related mortality. Overall, ruxolitinib was relatively well-tolerated and showed outcomes comparable to the REACH3 trial in a heavily pretreated patient population. [ABSTRACT FROM AUTHOR]
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- 2024
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27. The application of JAK inhibitors in the peri-transplantation period of hematopoietic stem cell transplantation for myelofibrosis.
- Author
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Wang, Zerong, Jin, Xuelian, Zeng, Jiajia, Xiong, Zilin, and Chen, Xinchuan
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HEMATOPOIETIC stem cell transplantation , *MYELOPROLIFERATIVE neoplasms , *GRAFT versus host disease , *OVERALL survival , *RUXOLITINIB , *MYELOFIBROSIS - Abstract
Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with a poor prognosis, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential. Ruxolitinib, a JAK1/2 inhibitor, has shown promising results in improving patients' symptoms, overall survival, and quality of life, and can be used as a bridging therapy to HSCT that increases the proportion of transplantable patients. However, the effect of this and similar drugs on HSCT outcomes is unknown, and the reports on their efficacy and safety in the peri-transplantation period vary widely in the published literature. This paper reviews clinical data related to the use of JAK inhibitors in the peri-implantation phase of hematopoietic stem cell transplantation for primary myelofibrosis and discusses their efficacy and safety. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Disability Associated with Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: Analysis of a Cross-Sectional US Patient Survey.
- Author
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Hamilton, Betty K., Williams, Paul, Galvin, John, Turnbull, James, and Yu, Jingbo
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HEMATOPOIETIC stem cell transplantation ,GRAFT versus host disease ,DISABILITIES ,SELF-evaluation ,CROSS-sectional method ,STATISTICAL correlation ,COGNITIVE testing ,WORK capacity evaluation ,RESEARCH funding ,TRANSPLANTATION of organs, tissues, etc. ,SEX distribution ,LOGISTIC regression analysis ,INDEPENDENT variables ,HOMOGRAFTS ,SYMPTOM burden ,MULTIVARIATE analysis ,CHI-squared test ,DESCRIPTIVE statistics ,CHRONIC diseases ,RACE ,RESEARCH methodology ,RESEARCH ,STATISTICS ,SOCIAL support ,CELLS ,LABOR supply ,ACTIVITIES of daily living ,NUTRITION ,REGRESSION analysis ,DISEASE complications - Abstract
Introduction: Chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT) is associated with poor health-related quality of life (HRQoL) and functional status. However, few studies have evaluated chronic GVHD–related disability and specific activity limitations from a patient perspective. The objective of this analysis was to assess physical, cognitive, and work disability, and describe factors predictive of disability in patients with chronic GVHD in the potentially employable general workforce. Methods: The cross-sectional, online, Living With Chronic GVHD Patient Survey was administered in 2020 to adult US patients who reported an active chronic GVHD diagnosis (i.e., within the previous 5 years) following HSCT. Data included demographics, diagnosis, work status, chronic GVHD symptoms per the Lee Symptom Scale (LSS), and effects on daily living activities. Descriptive and correlational analyses informed composite disability definitions: (1) severe cognitive disability, (2) severe physical disability, and (3) work disability. Results: Of 137 respondents with GVHD included in this analysis, 47.0% reported severe cognitive disability, and approximately two-thirds each reported severe physical disability (67.4%) and work disability (62.8%). Chronic GVHD severity/duration, symptoms (Lee Symptom Scale), and number of transplant specialists consulted were associated with all types of disability (univariable analyses). Severe cognitive disability was associated with the number of transplant specialists consulted, severe physical disability with female sex, and work disability with nonwhite race. Conclusions: In this analysis, we found that the presence of specific symptoms and the number of transplant specialists consulted were associated with all types of severe disability; female sex was predictive of severe physical disability and nonwhite race of work disability. These findings add to the understanding of chronic GVHD-associated disability, suggest a need for improved social support for patients, and highlight potential indicators for those most in need. Plain Language Summary: Chronic graft-versus-host disease (GVHD) is a possible serious complication that can occur after someone has received a bone marrow or stem cell transplant from another person. Symptoms of chronic GVHD can be severe and can affect quality of life. To better understand exactly how chronic GVHD affects quality of life, we asked adults in the USA with chronic GVHD to fill out a survey. The objective of this research was to find out how chronic GVHD affects daily activities and work. The survey asked about physical activities including personal hygiene, eating, shopping, and ability to use the restroom, and the survey asked about mental tasks including managing personal finances and interactions with other people. The survey also asked questions about work, such as the need to take disability leave or to leave a job due to chronic GVHD. Many people with chronic GVHD who completed the survey said they had severe difficulty with mental and/or physical tasks, and many had work-related disability. People with more severe chronic GVHD who had met with many transplant specialists were more likely to have difficulty with mental and physical tasks and also to have work disability. Women who completed the survey were more likely to report severe physical disability than men, and nonwhite participants were more likely to report work disability. The results of this survey highlight a need for improved social support for patients with chronic GVHD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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29. Characterization of ibrutinib's effects on the morphology, proliferation, phenotype, viability, and anti-inflammatory potential of adipose-derived mesenchymal stromal cells.
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Silva-Carvalho, Amandda Évelin, Bispo, Elizabete Cristina Iseke, da Silva, Ingrid Gracielle Martins, Correa, José Raimundo, Carvalho, Juliana Lott, Gelfuso, Guilherme Martins, and Saldanha-Araujo, Felipe
- Subjects
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STROMAL cells , *GRAFT versus host disease , *PHENOTYPES , *MORPHOLOGY , *CELL survival , *THROMBOPOIETIN receptors - Abstract
Ibrutinib (IB) is a tyrosine kinase inhibitor (TKI) that has immunomodulatory action and can be used as second-line therapy for steroid-refractory or steroid-resistant chronic Graft versus Host Disease (cGVHD). Mesenchymal stromal cells (MSCs) are distributed throughout the body and their infusion has also been explored as a second-line therapeutic alternative for the treatment of cGVHD. Considering the currently unknown effects of IB on endogenous MSCs, as well as the possible combined use of IB and MSCs for cGVHD, we investigated whether adipose tissue-derived MSCs present IB-targets, as well as the consequences of treating MSCs with this drug, regarding cell viability, proliferation, phenotype, and anti-inflammatory potential. Interestingly, we show for the first time that MSCs express several IB target genes. Also of note, the treatment of such cells with this TKI elevated the levels of CD90 and CD105 surface proteins, as well as VCAM-1. Furthermore, IB-treated MSCs presented increased mRNA expression of the anti-inflammatory genes PD-L1, TSG-6, and IL-10. However, continued exposure to IB, even at low doses, compromised the viability of MSCs. These data indicate that the use of IB can stimulate an anti-inflammatory profile in MSCs, but also that a continued exposure to IB can compromise MSC viability over time. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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30. Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.
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Lining Zhang, Jianping Li, Weiru Liang, Xiaoyu Zhang, Shulian Chen, Yuanyuan Shi, Mengze Hao, Xiaoli Zhao, Ming Gong, Jialin Wei, Yi He, Erlie Jiang, Mingzhe Han, Fengkui Zhang, and Sizhou Feng
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HEMATOPOIETIC stem cell transplantation ,APLASTIC anemia ,GRAFT versus host disease ,IMMUNOSUPPRESSIVE agents ,OVERALL survival - Abstract
The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Human umbilical cord-derived mesenchymal stromal cells for the treatment of steroid refractory grades III-IV acute graft-versus-host disease with long-term follow-up.
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Jing-wen Niu, Yuhang Li, Chen Xu, Hongxia Sheng, Chong Tian, Hongmei Ning, Jiangwei Hu, Jianlin Chen, Botao Li, Jun Wang, Xiao Lou, Na Liu, Yongfeng Su, Yao Sun, Zhuoqing Qiao, Lei Wang, Yu Zhang, Sanchun Lan, Jing Xie, and Jing Ren
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HEMATOPOIETIC stem cell transplantation ,GRAFT versus host disease ,STROMAL cells ,GASTROINTESTINAL system ,INTRAVENOUS therapy - Abstract
Introduction: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs. Methods: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 x 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16). Results: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2%vs. 58.8%; p=0.049). No patient experienced serious adverse events. Discussion: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging condition. (NCT01754454). [ABSTRACT FROM AUTHOR]
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- 2024
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32. Long‐term outcome after allogeneic stem cell transplantation for GATA2 deficiency: An analysis of 67 adults and children from France and Belgium.
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Sicre de Fontbrune, Flore, Chevillon, Florian, Fahd, Mony, Desseaux, Kristell, Poiré, Xavier, Forcade, Edouard, Sterin, Arthur, Neven, Bénédicte, Gandemer, Virginie, Thepot, Sylvain, Garnier, Alice, Lioure, Bruno, Marcais, Ambroise, Nguyen‐Quoc, Stephanie, Tavitian, Suzanne, Vincent, Laure, Donadieu, Jean, Resche Riggon, Matthieu, Chevret, Sylvie, and Pasquet, Marlene
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GRAFT versus host disease , *STEM cell transplantation , *HEMATOPOIETIC stem cells , *ACUTE myeloid leukemia , *HEMATOPOIETIC stem cell transplantation - Abstract
Summary Modalities and timing of haematopoietic stem cell transplant (HSCT) in patients with GATA2 deficiency are still subject to debate. On June 2022, 67 patients (median age 20.6 years) underwent a first allogeneic HSCT among 21 centres. Indications for HSCT were myelodysplastic syndrome (MDS) ≤5% blasts ± immunodeficiency (66%), MDS >5% blasts (15%), acute myeloid leukaemia (19%). Conditioning regimen was myeloablative in 85% and anti‐thymocyte globulins were used in 67%. The cumulative incidence (CInc) of acute graft versus host disease (GvHD) grade II–IV and III–IV at day 100 were 42% and 13%, and CInc of chronic and extensive chronic GvHD at 2 years were 42% and 23%. CInc of relapses was 3% and 11% at 1 and 5 years. Overall survival (OS) at 1 and 5 years was 83% and 72% (median follow‐up 5.6 years). The factors associated with worse OS in multivariable analysis were the year of HSCT, a history of excess blasts before transplant and peripheral blood stem cell (PBSC) grafts. Age at HSCT, non‐myeloablative conditioning and PBSC grafts were associated with increased non‐relapse mortality. In conclusion, bone marrow monitoring to identify clonal evolution and perform HSCT before the appearance of excess blast is mandatory. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Traversing the bench to bedside journey for iNKT cell therapies.
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O'Neal, Julie, Mavers, Melissa, Jayasinghe, Reyka G., and DiPersio, John F.
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GRAFT versus host disease ,KILLER cells ,CYTOTOXIC T cells ,CHIMERIC antigen receptors ,HEMATOPOIETIC stem cells - Abstract
Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT cell tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti- cancer efficacy. Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Better clinical outcomes and lower triggering of inflammatory cytokines for allogeneic hematopoietic cell transplant recipients treated in home care versus hospital isolation -- the Karolinska experience.
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Ringdén, Olle, Svahn, Britt-Marie, Moll, Guido, and Sadeghi, Behnam
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HEMATOPOIETIC stem cell transplantation ,ISOLATION (Hospital care) ,ECOLOGICAL houses ,GRAFT versus host disease ,PARENTERAL feeding - Abstract
After allogeneic hematopoietic cell transplantation (Allo-HCT) and conditioning, patients are typically placed in isolated hospital rooms to prevent neutropenic infections. Since 1998, we've offered an alternative: home care for patients living within a one to two-hour drive of the hospital. In Sweden this approach includes daily visits by an experienced nurse and daily phone consultations with a unit physician. When necessary, patients receive transfusions, intravenous antibiotics, and total parenteral nutrition at home. Our initial study report compared 36 home care patients with 54 hospital-treated controls. Multivariate analysis found that home care patients were discharged earlier to outpatient clinics, required fewer days of total parenteral nutrition, had less acute graft-versus-host disease (GVHD) grade II-IV, and lower transplantation-related mortality (TRM) and lower costs. Long-term follow-up showed similar chronic GVHD and relapse rates in both groups, with improved survival rates in the home care group. A subsequent comparison of 146 home care patients with hospital-treated controls indicated that home care and longer home stays were associated with lower grades of acute GVHD. Home care was found to be safe and beneficial for children and adolescents. Over two decades, 252 patients received home care post-Allo-HCT without any fatalities at-home. Ten-year outcomes showed a 14% TRM and a 59% survival rate. In 2020, an independent center confirmed the reduced risk of acute GVHD grades II-IV for patients treated in home care. Here, we report for the first time that home care patients also demonstrate a less inflammatory systemic cytokine profile. We found higher levels of IFN-γ, IL-2, IL-5, IL-13, GM-CSF, and G-CSF, but lower VEGF in hospital-treated patients, which may contribute to acute GVHD grades II-IV. In conclusion, home-based treatment following Allo-HCT yields multiple promising clinical outcomes and improved systemic inflammatory markers, which may contribute to less development of life-threatening GVHD. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Early intervention with oral mucosal barrier Protective agents in chronic oral graft-versus-host disease: a retrospective cohort study.
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Cao, Jianqiong, Ye, Lijuan, Li, Xiao, Song, Qiujin, and Chai, Yanyan
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GRAFT versus host disease ,SOMATOFORM disorders ,HEMATOPOIETIC stem cell transplantation ,EARLY medical intervention ,RESEARCH funding ,INDEPENDENT living ,REHABILITATION ,ORAL mucosa ,TREATMENT effectiveness ,RETROSPECTIVE studies ,DESCRIPTIVE statistics ,SEVERITY of illness index ,EMOTIONS ,LONGITUDINAL method ,QUALITY of life ,MEDICAL records ,ACQUISITION of data ,DISEASE progression ,ORAL health - Abstract
Background: Preventing the progression of chronic oral graft-versus-host disease (cGVHD) is essential for maintaining oral health, improving quality of life, minimizing functional impairment, reducing systemic complications, and addressing treatment challenges. Purpose: To evaluate the effectiveness of early intervention with oral mucosal barrier protective agents in preventing the progression of cGVHD and its impact on oral health, quality of life, and treatment response. Methods: This retrospective cohort study included 75 participants, with 34 in the non-oral mucosal barrier protective agent group and 41 in the oral mucosal barrier protective agent group. Baseline characteristics, oral mucosal health parameters, quality of life assessments, and curative effect data were collected and compared between the two study groups. Results: The group receiving oral mucosal barrier protectants (n = 41) exhibited significantly lower severity of oral mucositis compared to the group without such protectants (n = 34) (2.12 ± 0.48 vs. 2.56 ± 0.63, P = 0.001) and the incidence of complications was significantly lower in the group receiving oral mucosal barrier protectants (P < 0.05). Additionally, the quality of life assessment showed marked improvements in somatization, emotional management, and social reintegration in the oral mucosal barrier protectant group compared to the group without these protectants (P < 0.05). Furthermore, the assessment of treatment efficacy revealed significantly higher rates of both complete and partial responses in the oral mucosal barrier protectant group, along with a notable reduction in disease progression compared to the group without these protectants (P < 0.001). Conclusion: Early intervention with oral mucosal barrier protective agents was associated with improved oral health parameters, enhanced quality of life, and a more favorable treatment response in the context of cGVHD. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease.
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Koca, David Sinan and Dietrich-Ntoukas, Tina
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EYE drops , *GRAFT versus host disease , *IMMUNOSUPPRESSIVE agents , *ANTI-inflammatory agents , *STEROID drugs - Abstract
Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German–Austrian–Swiss Consensus (GAS) Grading were analyzed. Systemic GVHD manifestations as well as the prevalence of topical and systemic (immunomodulatory) therapies were assessed. Results: A total of 74 of 95 patients (77.8%) had manifestations of systemic chronic graft-versus-host disease other than ocular GVHD. 68.42% (65/95) of patients were under systemic immunosuppressive therapy with at least one immunosuppressive medication. All patients (95/95) received lid-margin hygiene and phosphate- and preservative-free lubricating eye drops. Twenty-five percent of the cohort (24/95) were treated with autologous serum eye drops (ASEDs). In total, 80% (76/95) of patients required topical steroid therapy to treat acute exacerbation of inflammation at least once; continuous topical steroid therapy was only necessary for a minor part (12%) with refractory chronic inflammation. A total of 92.63% (88/95) were primarily treated with ciclosporin A 0.1% as Ikervis®, of whom at least one third did not continue the therapy because of intolerable side effects during follow-up and received alternative topical formulations. Conclusions: Our data show that patients with ocular cGVHD mostly need topical therapy including anti-inflammatory agents despite systemic immunosuppressive therapy. In our cohort, 80% of patients received topical steroids, and more than 90% received topical ciclosporin A eye drops, which were tolerated by only two thirds of patients due to side effects. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Preliminary Data on SNP of Transplantation-Related Genes after Haploidentical Stem Cell Transplantation.
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Tseng, Ching-Ping, Lin, Tung-Liang, Tsai, Shu-Hui, Lin, Wei-Tzu, Hsu, Fang-Ping, Wang, Wei-Ting, and Chen, Ding-Ping
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HEMATOPOIETIC stem cell transplantation , *STEM cell transplantation , *HLA histocompatibility antigens , *SINGLE nucleotide polymorphisms , *GRAFT versus host disease - Abstract
Background: Hematopoietic stem cell transplantation (HSCT) is one of the mainstream treatments for patients with hematologic malignancies. The matching status of human leukocyte antigen (HLA) between the donor and recipient is highly related to the outcomes of HSCT. Haploidentical HSCT (haplo-HSCT) has emerged as a type of HSCT for patients who cannot find a fully HLA-matched donor. In this study, we investigated whether the single nucleotide polymorphisms (SNPs) of the HLA-related genes and the genes encoding co-stimulatory molecules located on the non-HLA region are related to the outcomes of haplo-HSCT. Methods: The genomic DNAs of 24 patients and their respective donors were isolated from the peripheral blood obtained before performing haplo-HSCT. A total of 75 SNPs of the HLA-related genes (HCP5, NOTCH4, HLA-DOA, LTA, HSPA1L, BAG6, RING1, TRIM27, and HLA-DOB) and the genes located in the non-HLA genes involved in co-stimulatory signaling (CTLA4, TNFSF4, CD28, and PDCD1) were selected to explore their relationship with the outcomes after haplo-HSCT, including graft-versus-host disease, survival status, and relapse. Results: Our data revealed that specific donor or patient SNPs, including rs79327197 of the HLA-DOA gene, rs107822 and rs213210 of the RING1 gene, rs2523676 of the HCP5 gene, rs5742909 of the CTLA4 gene, rs5839828 and rs36084323 of the PDCD1 gene, and rs1234314 of the TNFSF4 gene, were significantly related to the development of adverse outcomes post-haplo-HSCT. Conclusions: These SNPs may play important roles in post-transplant immune response that can be considered during the selection of suitable donors. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Treosulfan-Versus Melphalan-Based Reduced Intensity Conditioning in HLA-Haploidentical Transplantation for Patients ≥ 50 Years with Advanced MDS/AML.
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Fraccaroli, Alessia, Stauffer, Elena, Haebe, Sarah, Prevalsek, Dusan, Weiss, Lena, Dorman, Klara, Drolle, Heidrun, von Bergwelt-Baildon, Michael, Stemmler, Hans-Joachim, Herold, Tobias, and Tischer, Johanna
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THERAPEUTIC use of antineoplastic agents , *MYELODYSPLASTIC syndromes , *HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *STATISTICAL significance , *SCIENTIFIC observation , *KRUSKAL-Wallis Test , *FISHER exact test , *AGE distribution , *TREATMENT effectiveness , *RETROSPECTIVE studies , *CHI-squared test , *DESCRIPTIVE statistics , *MELPHALAN , *KAPLAN-Meier estimator , *MEDICAL records , *ACQUISITION of data , *CANCER patient psychology , *CONFIDENCE intervals , *DATA analysis software , *OVERALL survival - Abstract
Simple Summary: Relapse and treatment-related side effects pose significant challenges for older patients with high-risk blood cancers (myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)) undergoing hematopoietic stem cell transplants from HLA-haploidentical donors. We compared two preparative treatment regimens to identify the most tolerable and effective approach: one using fludarabine, cyclophosphamide, and melphalan, and the other using fludarabine, cyclophosphamide, and treosulfan. Our goal was to determine which treatment offers better survival rates and fewer side effects. We found that both regimens resulted in similar survival outcomes. However, the melphalan regimen was associated with fewer relapses but more treatment-related deaths, while the treosulfan regimen had fewer side effects but exhibited poorer disease control. These findings suggest that treosulfan may be safer, though higher doses might improve disease control, providing valuable insights for future treatments. Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable engraftment and low non-relapse mortality (NRM) in patients undergoing HLA-matched allo-HSCT. However, data on treosulfan-based conditioning in the HLA-haploidentical transplantation (HaploT) setting are limited. We retrospectively compared conditioning with fludarabine–cyclophosphamide (FC)–melphalan (110 mg/m2) and FC-treosulfan (30 g/m2) prior to HaploT using post-transplantation cyclophosphamide (PTCy) in patients with high-risk MDS/AML patients ≥ 50 years, transplanted from 2009–2021 at our institution (n = 80). After balancing patient characteristics by a matched-pair analysis, we identified twenty-one matched pairs. Two-year OS and LFS were similar among the groups (OS 66% and LFS 66%, p = 0.8 and p = 0.57). However, FC-melphalan was associated with a significantly lower probability of relapse compared to FC-treosulfan (0% vs. 24%, p = 0.006), counterbalanced by a higher NRM (33% vs. 10%, p = 0.05). Time to engraftment and incidences of acute and chronic graft-versus-host disease (GvHD) did not differ significantly. In conclusion, HaploT using FC-treosulfan in combination with PTCy in patients aged ≥50 years with MDS/AML appears safe and effective, particularly in advanced disease stages. We confirm the favorable extramedullary toxicity profile, allowing for potential dose intensification to enhance antileukemic activity. [ABSTRACT FROM AUTHOR]
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- 2024
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39. The Impact of Histologic Portal T-Cell Density on the Clinical Outcomes in Hepatic Graft-versus-Host Disease and Autoimmune Liver Diseases.
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Lee, Soon Kyu, Park, Sung-Soo, Park, Silvia, Lee, Sung-Eun, Cho, Byung-Sik, Eom, Ki-Seong, Kim, Yoo-Jin, Kim, Hee-Je, Min, Chang-Ki, Cho, Seok-Goo, Lee, Jong Wook, Lee, Seok, Kim, Younghoon, Han, Ji Won, Yang, Hyun, Bae, Si Hyun, Jang, Jeong Won, Choi, Jong Young, Yoon, Seung Kew, and Lee, Dong Yeup
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AUTOIMMUNE hepatitis , *GRAFT versus host disease , *HEMATOPOIETIC stem cells , *STEM cell transplantation , *AUTOIMMUNE diseases , *HEPATIC veno-occlusive disease - Abstract
Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease. We analyzed 78 patients with biopsy-confirmed hepatic GVHD (n = 38) or autoimmune liver disease (n = 40) between 2016 and 2021. The cholestatic variant was defined by an R-value < 2.0, based on the ratio of alanine aminotransferase to alkaline phosphatase. The primary outcome was the biochemical response at 4 (early) and 8–12 (late) weeks after corticosteroid treatment. In hepatic GVHD patients, the hepatitic variant (n = 19) showed greater CD3+ T-cell infiltration than the cholestatic variant (n = 19; p < 0.001). No significant differences were observed in the infiltration of CD20+, CD38+, or CD68+ cells. The hepatitic variant had significantly better early and late responses and higher liver-related event-free survival than the cholestatic variants (p < 0.05). Concerning autoimmune liver diseases, the autoimmune hepatitis (AIH) group had significantly more portal T-cell infiltration and better treatment responses than the primary biliary cholangitis (PBC) group. In conclusion, higher portal T-cell infiltration may be associated with better clinical outcomes in patients with hepatic GVHD. Additionally, this study highlights similarities in portal T-cell infiltration and treatment response patterns between AIH and the hepatitic variant, as well as PBC and the cholestatic variant. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.
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Ghanbari Sevari, Faezeh, Mehdizadeh, Amir, Abbasi, Khadijeh, Hejazian, Seyyed Sina, and Raisii, Mortaza
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CYTOTOXIC T cells , *GRAFT versus host disease , *KILLER cells , *HEMATOLOGIC malignancies , *CYTOTOXINS , *T cells , *ALEMTUZUMAB - Abstract
Background: Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC‐unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment‐related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies. Main body: CIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3−/CD56+ NK cells, and CD3+/CD56− cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKs-based therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content of T cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings. Conclusion: CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Cautious Optimism Warranted for Stem Cell-Derived Islet Transplantation in Type 2 Diabetes.
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Scholz, Hanne, Sordi, Valeria, and Piemonti, Lorenzo
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MEDICAL sciences , *INDUCED pluripotent stem cells , *GRAFT versus host disease , *PANCREATIC beta cells , *TYPE 2 diabetes , *HYPERGLYCEMIA , *BK virus - Abstract
A recent study published in Transplant International explores the use of stem cell-derived islet transplantation as a potential treatment for type 2 diabetes. The study details the successful transplantation of islet tissue derived from induced pluripotent stem cells into a patient with type 2 diabetes, which resulted in improved islet function. However, the study also acknowledges the need for more information on quality control and the limitations of diagnosing the patient's diabetes. The authors suggest that further research is necessary to fully understand the safety and effectiveness of this treatment. The document provides a summary of the study, including information on its focus, findings, and the authors' contributions and funding. [Extracted from the article]
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- 2024
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42. Specific antigen-based stratification of membranous nephropathy in patients after haematopoietic stem cell allotransplantation - a case series and literature review.
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Bosnić Kovačić, Ines, Matošević, Matija, Laganović, Mario, Dika, Živka, Fištrek Prlić, Margareta, Ivandić, Ema, Ćorić, Marijana, Bulimbašić, Stela, Duraković, Nadira, Perić, Zinaida, Desnica, Lana, Vrhovac, Radovan, Jelaković, Bojan, Sethi, Sanjeev, and Vuković Brinar, Ivana
- Subjects
HEMATOPOIETIC stem cell transplantation ,GRAFT versus host disease ,HEMATOPOIETIC stem cells ,STEM cell transplantation ,ACUTE myeloid leukemia - Abstract
Background: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. Case presentations: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. Conclusions: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen.
- Author
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Horwitz, David A., Ju Hua Wang, Dongin Kim, Chang Kang, Brion, Katja, Bickerton, Sean, and La Cava, Antonio
- Subjects
REGULATORY T cells ,T cells ,IMMUNOSUPPRESSION ,GRAFT versus host disease ,GRAFT rejection - Abstract
We have previously reported that nanoparticles (NPs) loaded with IL-2 and TGF-β and targeted to T cells induced polyclonal T regulatory cells (Tregs) that protected mice from graft-versus-host disease (GvHD). Here, we evaluated whether administration of these NPs during alloantigen immunization could prevent allograft rejection by converting immunogenic responses to tolerogenic ones. Using C57BL/6 mice and BALB/c mice as either donors or recipients of allogeneic splenocytes, we found that treatment with the tolerogenic NPs in both strains of mice resulted in a marked inhibition of mixed lymphocyte reaction (MLR) to donor cell alloantigen but not to third-party control mouse cells after transfer of the allogeneic cells. The decreased alloreactivity associated with a four- to fivefold increase in the number of CD4
+ and CD8+ T regulatory cells (Tregs) and the acquisition of a tolerogenic phenotype by recipient dendritic cells (DCs) in NP-treated mice. As allogeneic cells persisted in NP-treated mice, these findings suggest that tolerogenic NPs can induce alloantigen-specific Tregs and tolerogenic DCs promoting tolerogenic responses to alloantigen. By inhibiting reactivity to allotransplant, this approach could help reduce the need for immune suppression for the maintenance of allografts. [ABSTRACT FROM AUTHOR]- Published
- 2024
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44. CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice.
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Kang-Hyun Kim, Sang-wook Lee, In-Jeoung Baek, Hye-Young Song, Seon-Ju Jo, Je-Won Ryu, Seung-Hee Ryu, Jin-Hee Seo, Jong-Choon Kim, and Seung-Ho Heo
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HEMATOPOIETIC stem cells ,HLA histocompatibility antigens ,KNOCKOUT mice ,GRAFT versus host disease ,BIOLOGICAL systems - Abstract
Introduction: Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47
null Rag2null IL-2rγnull (RTKO) mice, and applied it to generate humanized mice. Methods: Four-week-old female NOD-Rag2null IL-2rγnull (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection. Results: For a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines. Discussion: Humanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields. [ABSTRACT FROM AUTHOR]- Published
- 2024
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45. Risk factors of bloodstream infection after allogeneic hematopoietic cell transplantation in children/adolescent and young adults.
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Sajiki, Daichi, Muramatsu, Hideki, Wakamatsu, Manabu, Yamashita, Daiki, Maemura, Ryo, Tsumura, Yusuke, Imaya, Masayuki, Yamamori, Ayako, Narita, Kotaro, Kataoka, Shinsuke, Taniguchi, Rieko, Narita, Atsushi, Nishio, Nobuhiro, and Takahashi, Yoshiyuki
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PERIPHERALLY inserted central catheters , *HEMATOPOIETIC stem cell transplantation , *YOUNG adults , *GRAM-positive bacteria , *GRAFT versus host disease - Abstract
Allogeneic hematopoietic cell transplantation (HCT) is a crucial treatment for various diseases, including hematological malignancies, solid tumors, and genetic disorders. Despite its curative potential, HCT is associated with severe complications, notably infections, graft-versus-host disease, and organ damage. Infections, particularly bloodstream infections (BSIs), pose a significant threat in the initial weeks post-HCT, necessitating effective management strategies. This retrospective study aimed to clarify the incidence, pathogens, and risk factors associated with BSI within the first 30 days after allogeneic HCT in children/adolescents and young adults (AYAs). The study included 115 patients aged <31 years who underwent 121 allogeneic HCTs at the Department of Pediatrics, Nagoya University Hospital between January 1, 2018, and March 31, 2022. Data encompassed demographic characteristics, HCT details, and BSI information. Overall, 27 of 121 patients developed BSI with the cumulative incidence of 23.5% (95% confidence intervals [CI]: 17.0%–30.6%) at 30 days after HCT. The median onset time of BSI was 7 (range, 4–26 days) after HCT. Gram-positive bacteria accounted for 89% of pathogens isolated from blood cultures, with Streptococcus mitis/oralis being the most common. In multivariable analysis, tandem HCT (subdistribution hazard ratio [SHR]: 5.67, 95% CI: 2.74–11.7, p < 0.001) and peripherally inserted central catheters (SHR: 2.96, 95% CI: 1.34–6.55, p = 0.007) were identified as independent risk factors for BSI. In patients receiving tandem HCT, the pathogens isolated from blood cultures were all gram-positive bacteria, with Streptococcus mitis/oralis accounting for up to 67% of the isolated pathogens. Tandem HCT and PICCs were identified as independent risk factors for BSI after allogeneic HCT in children/AYAs. The pathogens were commonly gram-positive, and Streptococcus mitis/oralis is important in patients who received tandem HCT. These data can provide valuable information for future studies to consider effective interventions to reduce the risk of BSI in high-risk patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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46. Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.
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Han, Lijie, Sun, Xianlei, Kong, Jingjing, Li, Jin, Feng, Kai, Bai, Yanliang, Wang, Xianjing, Zhu, Zhenhua, Yang, Fengyuan, Chen, Qingzhou, Zhang, Mengmeng, Yue, Baohong, Wang, Xiaoqian, Fu, Liyan, Chen, Yaoyao, Yang, Qiankun, Wang, Shuya, Xin, Qingxuan, Sun, Nannan, and Zhang, Danfeng
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HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *BILE acids , *GUT microbiome , *T cells - Abstract
Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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47. EBV Reactivation and Disease in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients and Its Impact on HSCT Outcomes.
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Law, Nancy, Logan, Cathy, and Taplitz, Randy
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STEM cell transplantation , *HEMATOPOIETIC stem cells , *GRAFT versus host disease , *EPSTEIN-Barr virus diseases , *LYMPHOPROLIFERATIVE disorders - Abstract
The acquisition or reactivation of Epstein–Barr virus (EBV) after allogeneic Hematopoietic Stem Cell Transplant (HSCT) can be associated with complications including the development of post-transplant lymphoproliferative disorder (PTLD), which is associated with significant morbidity and mortality. A number of risk factors for PTLD have been defined, including T-cell depletion, and approaches to monitoring EBV, especially in high-risk patients, with the use of preemptive therapy upon viral activation have been described. Newer therapies for the preemption or treatment of PTLD, such as EBV-specific cytotoxic T-cells, hold promise. Further studies to help define risks, diagnosis, and treatment of EBV-related complications are needed in this at-risk population. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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48. Recent infection with SARS‐CoV‐2 in donors was associated with a higher incidence of acute graft‐versus‐host disease in recipients undergoing allogeneic haematopoietic stem cell transplantation.
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Lin, Fan, Xu, Lanping, Han, Tingting, Xu, Zhengli, Liu, Jing, He, Yun, Chen, Yao, Chen, Huan, Han, Wei, Chen, Yuhong, Fu, Haixia, Zhang, Yuanyuan, Mo, Xiaodong, Wang, Fengrong, Wang, Jingzhi, Cheng, Yifei, Yan, Chenhua, Sun, Hui, Wang, Yu, and Zhang, Xiaohui
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HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *STEM cell donors , *ACUTE diseases , *TREATMENT effectiveness - Abstract
Summary: The global pandemic has resulted in the common occurrence of SARS‐CoV‐2 infection in the population. In the post‐pandemic era, it is imperative to understand the influence of donor SARS‐CoV‐2 infection on outcomes after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). We retrospectively analysed allo‐HSCTs from donors with mild SARS‐CoV‐2 infection or early recovery stage (ERS) (group 1, n = 65) and late recovery stage (group 2, n = 120). Additionally, we included allo‐HSCT from donors without prior SARS‐CoV‐2 infection as group 0 (n = 194). Transplants from donors with different SARS‐CoV‐2 infection status had comparable primary engraftment and survival rates. However, group 1 had higher incidences of acute graft‐versus‐host disease (aGvHD), grade II–IV (41.5% vs. 28.1% in group 0 [p = 0.014] and 30.6% in group 2 [p = 0.067]) and grade III–IV (22.2% vs. 9.6% [p = 0.004] in group 0 and 12.2% in group 2 [p = 0.049]). Conversely, the risk of aGvHD in group 2 was similar to that in group 0 (p > 0.5). Multivariable analysis identified group 1 associated with grade II–IV (hazard ratio [HR] 2.307, p = 0.010) and grade III–IV (HR 2.962, p = 0.001) aGvHD, which yielded no significant risk factors for survival. In conclusion, we preliminarily demonstrated donors in the active infection state or ERS of mild SARS‐CoV‐2 infection were associated with higher incidences of aGvHD in transplants from related donors. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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49. Comparing the Differences in Adverse Events among Chimeric Antigen Receptor T-Cell Therapies: A Real-World Pharmacovigilance Study.
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Guo, Zihan, Ding, Yunlan, Wang, Mengmeng, Zhai, Qing, Liu, Jiyong, and Du, Qiong
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GRAFT versus host disease , *CEREBRAL hemorrhage , *CARDIO-renal syndrome , *CHIMERIC antigen receptors , *INTRACRANIAL hemorrhage - Abstract
In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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50. Post‐transplant‐cyclophosphamide and short‐term Everolimus as graft‐versus‐host‐prophylaxis in patients with relapsed/refractory lymphoma and myeloma—Final results of the phase II OCTET‐EVER trial.
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Richardson, Tim, Scheid, Christof, Herling, Marco, Frenzel, Lukas P., Herling, Carmen, Aguilar, Marta Rebecca Cruz, Theurich, Sebastian, Hallek, Michael, and Holtick, Udo
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STEM cell transplantation , *GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *EVEROLIMUS , *MULTIPLE myeloma - Abstract
Background: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft‐versus‐tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti‐cancer immune response. Methods: We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI‐free approach consisting of post‐transplant cyclophosphamide (PTCy) and short‐term Everolimus after reduced‐intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD. Results: Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow‐up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD‐relapse‐free‐survival was 47% after 3 years. Conclusions: Using PTCy and short‐term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non‐relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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