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12 pages, 1317 KiB  
Article
Impact of the Recipient’s Pre-Treatment Blood Lymphocyte Count on Intended and Unintended Effects of Anti-T-Lymphocyte Globulin in Allogeneic Hematopoietic Stem Cell Transplantation
by Alexander Nikoloudis, Veronika Buxhofer-Ausch, Christoph Aichinger, Michaela Binder, Petra Hasengruber, Emine Kaynak, Dagmar Wipplinger, Robert Milanov, Irene Strassl, Olga Stiefel, Sigrid Machherndl-Spandl, Andreas Petzer, Ansgar Weltermann and Johannes Clausen
Cells 2023, 12(14), 1831; https://doi.org/10.3390/cells12141831 - 12 Jul 2023
Cited by 2 | Viewed by 1543
Abstract
Background: In allogeneic hematopoietic stem cell transplantation (HSCT), Anti-T-Lymphocyte Globulin (ATLG) may be used for the prevention of severe graft-versus-host disease (GVHD). ATLG targets both the recipient’s lymphocytes and those transferred with the graft. Assuming an inverse relation between the recipient’s absolute lymphocyte [...] Read more.
Background: In allogeneic hematopoietic stem cell transplantation (HSCT), Anti-T-Lymphocyte Globulin (ATLG) may be used for the prevention of severe graft-versus-host disease (GVHD). ATLG targets both the recipient’s lymphocytes and those transferred with the graft. Assuming an inverse relation between the recipient’s absolute lymphocyte count (ALC) and exposure of remaining ATLG to the graft, we aim to evaluate the impact of the recipient’s ALC before the first ATLG administration on the benefits (prevention of GVHD and GVHD-associated mortality) and potential risks (increased relapse incidence) associated with ATLG. Methods: In recipients of HLA-matched, ATLG-based HSCT (n = 311), we assessed the incidence of acute GVHD, GVHD-related mortality and relapse, as well as other transplant-related outcomes, in relation to the respective ALC (divided into tertiles) before ATLG. Results: The top-tertile ALC group had a significantly increased risk of aGVHD (subhazard ratio (sHR) 1.81; [CI 95%; 1.14–2.88]; p = 0.01) and aGVHD-associated mortality (sHR 1.81; [CI 95%; 1.03–3.19]; p = 0.04). At the highest ATLG dose level (≥45 mg/kg), recipients with lowest-tertile ALC had a trend towards increased relapse incidence (sHR 4.19; [CI 95%; 0.99–17.7]; p = 0.05, n = 32). Conclusions: ATLG dosing based on the recipient’s ALC may be required for an optimal balance between GVHD suppression and relapse prevention. Full article
(This article belongs to the Special Issue Advances in Allogeneic Cell Therapy)
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13 pages, 1077 KiB  
Article
Graft-Versus-Host Disease Prophylaxis with Antithymocyte Globulin in Patients Receiving Stem Cell Transplantation from Unrelated Donors: An Observational Retrospective Single-Center Study
by Mariella Lo Schirico, Roberto Passera, Jessica Gill, Chiara Dellacasa, Irene Dogliotti, Luisa Giaccone, Sofia Zompi and Alessandro Busca
Cancers 2023, 15(10), 2761; https://doi.org/10.3390/cancers15102761 - 15 May 2023
Cited by 1 | Viewed by 1885
Abstract
Graft-versus-host disease (GVHD) is one of the most important complications of allogeneic hematopoietic stem cell transplantation. Rabbit antilymphocyte serum (ATG/ATLG) is recommended for GVHD prophylaxis, while its appropriate dosing is debated. We performed a retrospective single-center study to examine the outcome of patients [...] Read more.
Graft-versus-host disease (GVHD) is one of the most important complications of allogeneic hematopoietic stem cell transplantation. Rabbit antilymphocyte serum (ATG/ATLG) is recommended for GVHD prophylaxis, while its appropriate dosing is debated. We performed a retrospective single-center study to examine the outcome of patients receiving ATG at the dose of 5 mg/kg as GVHD prophylaxis for unrelated donor (URD) HSCT. We collected data from all consecutive adult patients with hematological malignancies who had undergone allogeneic HSCT from URDs at the Stem Cell Transplant Center of the Città della Salute e della Scienza Hospital of Torino between July 2008 and July 2021. The primary aim was to ascertain the cumulative incidence (CI) for acute GVHD (aGVHD) and chronic GVHD (cGVHD); the secondary aim was to ascertain the CI for NRM (Non-Relapse Mortality) and RI (Relapse Incidence), as well the overall survival (OS) and infection incidence within 30 days of transplantation. We included in the analysis 226 patients who collectively underwent 231 HSCTs. The CI of grade II–IV aGVHD was found to be 29.9%, while that of moderate to severe cGVHD was 29.8%. The CI of NRM recorded at 1, 2, and 3 years after transplant was 18.2%, 19.6%, and 20.2%, respectively. The CI of RI at 1, 2, and 3 years from transplant was recorded to be 17.8%, 21.0%, and 21.6%, respectively. The median follow-up was 56 months, while the median OS for the whole cohort was not established; the OS at 1, 3, and 5 years from transplant was 69.6%, 59.3%, and 57.2%, respectively. We registered 88 bacteremias in 82/231 patients (35.5%), while invasive fungal infections occurred in 12/231 patients (5.2%). Our study suggests that the use of ATG at 5 mg/kg is highly effective in limiting the occurrence of both aGVHD and cGVHD, ensuring a low NRM, RI, and infection incidence. Full article
(This article belongs to the Special Issue Autologous and Allogeneic Stem Cell Transplant in Cancer Therapy)
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16 pages, 4766 KiB  
Article
Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation
by Alexander Nikoloudis, Irene Strassl, Michaela Binder, Olga Stiefel, Dagmar Wipplinger, Robert Milanov, Christoph Aichinger, Emine Kaynak, Sigrid Machherndl-Spandl, Veronika Buxhofer-Ausch, Alexandra Böhm, Andreas Petzer, Ansgar Weltermann, Dominik Wolf, David Nachbaur and Johannes Clausen
Transplantology 2023, 4(1), 22-37; https://doi.org/10.3390/transplantology4010005 - 17 Feb 2023
Cited by 3 | Viewed by 2585
Abstract
Background: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a setting where methotrexate (MTX) and a calcineurin [...] Read more.
Background: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a setting where methotrexate (MTX) and a calcineurin inhibitor (CNI) are used as the backbone of GVHD prophylaxis. The efficacy of ATLG in combination with CNI and mycophenolate mofetil (MMF) has not been investigated as much, particularly in terms of a direct comparison with its effects when combined with CNI/MTX. A total of 401 HSCTs from two Austrian transplant centers were retrospectively evaluated. We included peripheral blood transplants from early- or intermediate-stage (excluding advanced/refractory) hematological diseases from matched siblings or 10/10 or 9/10 matched unrelated donors with CNI/MTX or CNI/MMF prophylaxis, either without (n = 219) or with ATLG (n = 182). Overall, ATLG significantly reduced the risk for all-cause mortality by multivariate Cox analysis (HR 0.53; p = 0.002). Stratification by postgrafting prophylaxis type revealed a significant survival advantage for ATLG in the CNI/MMF cohort (HR 0.49; p = 0.001; n = 193), while its effect on survival in the CNI/MTX cohort was not significant (HR 0.87; p = 0.56; n = 208). In unrelated HSCT with CNI/MMF prophylaxis, ATLG exhibited its greatest survival benefit (HR 0.34; p = 0.001; n = 104). In the context of CNI/MMF, ATLG may provide even greater benefits than in the setting of CNI/MTX for post-grafting immunosuppression. Future prospective studies on ATLG should therefore focus on CNI/MMF-based transplants, which are widely performed in elderly or comorbid patients not expected to tolerate a standard course of MTX. Full article
(This article belongs to the Section Artificial Organs, Stem Cells and Xenotransplantation)
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9 pages, 369 KiB  
Article
Association between Homophobia and Sociodemographic Characteristics in Health Workers in Southern Chile
by Oscar Oyarce-Vildósola, Alejandra Rodríguez-Fernández and Eduard Maury-Sintjago
Int. J. Environ. Res. Public Health 2022, 19(21), 13749; https://doi.org/10.3390/ijerph192113749 - 22 Oct 2022
Cited by 10 | Viewed by 2320
Abstract
Homophobic attitude in health workers is a social determinant in the health of the homosexual population because it affects healthcare and its access and equity. The objective was to determine the relationship between the level of homophobia and sociodemographic characteristics of primary health [...] Read more.
Homophobic attitude in health workers is a social determinant in the health of the homosexual population because it affects healthcare and its access and equity. The objective was to determine the relationship between the level of homophobia and sociodemographic characteristics of primary health workers in southern Chile. This was an analytical cross-sectional study. The sample consisted of 491 public servants from health centers in southern Chile. The attitudes toward lesbians and gay men (ATLG) scale was applied, and a binary logistic regression model was performed to evaluate the association. The study participants were predominantly women (76.0%), under 40 years of age (63.5%), heterosexuals (93.5%), and unpartnered (68.2%) but with children (61.7%), and they also had an educational attainment ≥ 12 years (66.6%). About 87.6% of the participants held healthcare positions, and the majority were religious believers (74.3%) and had a centrist political affiliation (51.0%). Results indicated that 34% of the participants exhibited homophobic attitudes; there were statistically significant differences with respect to age, number of children, educational attainment, religion, and political affiliation (p < 0.01). These were higher in individuals ≥40 years of age, with ≥3 children, with educational attainment ≥ 12 years, holding a healthcare position, who were religious believers, and who had right-wing political affiliation. Full article
18 pages, 767 KiB  
Article
How Context Matters: Change and Persistence of Homophobic Attitudes among Cameroonian Migrants in Switzerland
by Frida Lyonga
Sexes 2022, 3(4), 515-532; https://doi.org/10.3390/sexes3040038 - 18 Oct 2022
Cited by 2 | Viewed by 5080
Abstract
Debates on human rights in recent years have brought to the fore stark fault lines between African countries, where societal intolerance towards homosexuality is prevalent, and Western countries, which hold more tolerant views towards homosexuality. As contention rages around African identity and homosexuality, [...] Read more.
Debates on human rights in recent years have brought to the fore stark fault lines between African countries, where societal intolerance towards homosexuality is prevalent, and Western countries, which hold more tolerant views towards homosexuality. As contention rages around African identity and homosexuality, one interesting question calls for attention: how do the attitudes of Africans towards homosexuality evolve—or not—when they migrate from their home context to a more open society where homosexuality is widely accepted? This study draws on Herek’s ‘attitudes toward lesbians and gay men scale’ (ATLG) to investigate homophobia among Cameroonians at home compared to Cameroonian migrants in Switzerland and uses in-depth interviews to understand the reasons for any change in or persistence of attitudes. Survey data shows that Cameroonian migrants in Switzerland portray significantly less homophobia compared to Cameroonians living at home. Qualitative analysis identified four factors that contributed to change in attitudes among Cameroonian migrants: (i) experiencing racial prejudice and xenophobia prompted self-reflection about their own prejudices towards others; (ii) witnessing, first-hand, the huge infrastructure and development gap between their host and home country exposed anti-homosexuality politics back home as a needless distraction from actual development priorities; (iii) greater opportunities to meet and interact with gay people in the host country challenged long-held home-grown stereotypes about homosexuality; and (iv) non-discrimination standards and codes of conduct in the workplace in the host country encouraged conformity and shifts towards greater tolerance. Full article
(This article belongs to the Special Issue Exclusive Papers Collection of the Editorial Board of Sexes)
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11 pages, 432 KiB  
Article
Addition of a Single Low Dose of Anti T-Lymphocyte Globulin to Post-Transplant Cyclophosphamide after Allogeneic Hematopoietic Stem Cell Transplant: A Pilot Study
by Elisabetta Xue, Francesca Lorentino, Maria Teresa Lupo Stanghellini, Fabio Giglio, Simona Piemontese, Daniela Teresa Clerici, Francesca Farina, Sara Mastaglio, Alessandro Bruno, Edoardo Campodonico, Rosamaria Nitti, Magda Marcatti, Andrea Assanelli, Consuelo Corti, Fabio Ciceri, Jacopo Peccatori and Raffaella Greco
J. Clin. Med. 2022, 11(4), 1106; https://doi.org/10.3390/jcm11041106 - 19 Feb 2022
Cited by 13 | Viewed by 2972
Abstract
Correlation between risk of graft-versus-host disease (GvHD) and CD3+ counts within the peripheral blood stem cell graft has recently been reported in the setting of post-transplant cyclophosphamide (PT-Cy). We aimed to investigate the benefit of the addition of a single dose of [...] Read more.
Correlation between risk of graft-versus-host disease (GvHD) and CD3+ counts within the peripheral blood stem cell graft has recently been reported in the setting of post-transplant cyclophosphamide (PT-Cy). We aimed to investigate the benefit of the addition of a single dose of anti-T lymphocyte globulin (ATLG 5 mg/kg) to PT-Cy in this setting. Starting in 2019, all patients receiving PBSC transplant containing CD3+ counts above 300 × 106/kg (study group) received a post-transplant dose of ATLG in addition to standard PT-Cy. The study was designed as a real-life analysis and included all consecutive Hematopoietic Stem Cell Transplantation (HSCT) recipients according to the above-mentioned inclusion criterion (n = 21), excluding cord blood and bone marrow donors. Using a 1:2 matched-pair analysis, we compared the outcomes with a historical population who received PT-Cy only (control group). We found a delayed platelet engraftment (29% vs. 45% at 30 days, p = 0.03) and a non-significant trend toward higher risk of poor graft function (29% vs. 19%, p = 0.52). The addition of ATLG impacted long-term immune reconstitution on the CD4+ subsets, but this did not translate into higher rate of relapse or viral infection. Acute GvHD was not significantly impacted, but 1-year cumulative incidence of chronic GvHD was significantly lower in the study group (15% vs. 41%, p = 0.04). Survival outcomes were comparable. In conclusion PT-Cy and ATLG was overall safe and translated into a low rate of chronic GvHD incidence. Full article
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12 pages, 3657 KiB  
Article
Perioperative Perfusion of Allografts with Anti-Human T-lymphocyte Globulin Does Not Improve Outcome Post Liver Transplantation—A Randomized Placebo-Controlled Trial
by Paul Viktor Ritschl, Julia Günther, Lena Hofhansel, Stefanie Ernst, Susanne Ebner, Arne Sattler, Sascha Weiß, Annemarie Weissenbacher, Rupert Oberhuber, Benno Cardini, Robert Öllinger, Matthias Biebl, Christian Denecke, Christian Margreiter, Thomas Resch, Stefan Schneeberger, Manuel Maglione, Katja Kotsch and Johann Pratschke
J. Clin. Med. 2021, 10(13), 2816; https://doi.org/10.3390/jcm10132816 - 25 Jun 2021
Viewed by 2165
Abstract
Due to the lack of suitable organs transplant surgeons have to accept unfavorable extended criteria donor (ECD) organs. Recently, we demonstrated that the perfusion of kidney organs with anti-human T-lymphocyte globulin (ATLG) prior to transplantation ameliorates ischemia-reperfusion injury (IRI). Here, we report on [...] Read more.
Due to the lack of suitable organs transplant surgeons have to accept unfavorable extended criteria donor (ECD) organs. Recently, we demonstrated that the perfusion of kidney organs with anti-human T-lymphocyte globulin (ATLG) prior to transplantation ameliorates ischemia-reperfusion injury (IRI). Here, we report on the results of perioperative ATLG perfusion in a randomized, single-blinded, placebo-controlled, feasibility trial (RCT) involving 30 liver recipients (LTx). Organs were randomly assigned for perfusion with ATLG/Grafalon® (AP) (n = 16) or saline only (control perfusion = CP) (n = 14) prior to implantation. The primary endpoint was defined as graft function reflected by aspartate transaminase (AST) values at day 7 post-transplantation (post-tx). With respect to the primary endpoint, no significant differences in AST levels were shown in the intervention group at day 7 (AP: 53.0 ± 21.3 mg/dL, CP: 59.7 ± 59.2 mg/dL, p = 0.686). Similarly, exploratory analysis of secondary clinical outcomes (e.g., patient survival) and treatment-specific adverse events revealed no differences between the study groups. Among liver transplant recipients, pre-operative organ perfusion with ATLG did not improve short-term outcomes, compared to those who received placebo perfusion. However, ATLG perfusion of liver grafts was proven to be a safe procedure without the occurrence of relevant adverse events. Full article
(This article belongs to the Special Issue Liver Transplantation: Improving Results under Worsening Conditions)
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