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Biomedicines
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Novel Prophylactic and Therapeutic Strategies for Acute Graft versus Host...
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Novel Prophylactic and Therapeutic Strategies for Acute Graft versus Host Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 13208

Special Issue Editor

Dr. Zoltan Pos

E-Mail Website
Guest Editor
Department of Genetics, Cell and Immunobiology, Semmelweis University, 4 Nagyvarad ter, VII/709, 1089 Budapest, Hungary
Interests: CD8+ T cell response; acute graft versus host disease; allogeneic hematopoietic stem cell transplantation; T cell homing; gut-homing T cells; adoptive T cell transfer

Special Issue Information

Dear Colleagues,

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for a wide variety of hematopoietic disorders, immunodeficiencies, and malignancies. Acute graft versus host disease (aGVHD) is one of the most common adverse events of allo-HSCT, induced by rapid infiltration of typical target organs, most frequently the gut and the skin, by graft-derived alloreactive donor T cell-recognizing alloantigens of the recipient. As widespread alloreactive T cell activation, subsequent clonal expansion, and T cell mediated cytotoxicity may cause severe organ damage, aGvHD can develop into a serious condition that is often fatal despite treatment.

In recent years, major advances have been made both in GvHD prophylaxis and therapy. In addition to corticosteroids, several novel, targeted therapies have been proposed, evaluated in preclinical studies, or successfully introduced in the treatment of aGvHD.

Among others, these include monoclonals targeting inflammatory cytokines, T cell receptors, T cell homing regulators, the application of selective kinase inhibitors, the use of extracorporeal photopheresis, adoptive transfer of MSC and Treg cells, fecal microbiota transplants, and several other approaches. Nevertheless, despite these improvements, aGvHD is still associated with significant morbidity and mortality. Addressing severe GvHD remains an unmet need, and survival rates of corticosteroid-refractory aGvHD are abysmal.

This Special Issue is dedicated to biologics that can improve prevention or treatment of aGvHD.

Dr. Zoltan Pos
Guest Editor

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Keywords

  • Acute graft versus host disease
  • Monoclonal antibodies
  • Kinase inhibitors
  • Fetal microbiota transplantation
  • Adoptive treg transfer
  • Mesenchymal stem cell therapy

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Published Papers (4 papers)

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Research

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13 pages, 1343 KiB  
Article
Effective Extracorporeal Photopheresis of Patients with Transplantation Induced Acute Intestinal GvHD and Bronchiolitis Obliterans Syndrome
by Robin Reschke, Stephanie Zimmerlich, Christine Döhring, Gerhard Behre and Mirjana Ziemer
Biomedicines 2022, 10(8), 1887; https://doi.org/10.3390/biomedicines10081887 - 4 Aug 2022
Cited by 5 | Viewed by 1969
Abstract
Background: Patients with steroid-refractory intestinal acute graft-versus-host disease (aGvHD) and bronchiolitis obliterans syndrome (BOS) represent a population with a high need for alternative and effective treatment options. Methods: We report real-life data from 18 patients treated with extracorporeal photopheresis (ECP). This [...] Read more.
Background: Patients with steroid-refractory intestinal acute graft-versus-host disease (aGvHD) and bronchiolitis obliterans syndrome (BOS) represent a population with a high need for alternative and effective treatment options. Methods: We report real-life data from 18 patients treated with extracorporeal photopheresis (ECP). This cohort consisted of nine patients with steroid-refractory intestinal aGvHD and nine patients with BOS. Results: We document partial or complete clinical response and reduction of symptoms in half of the patients with intestinal acute GvHD and patients with BOS treated ECP. Responding patients tended to stay on treatment longer. In patients with BOS, stabilization of lung function and forced expiratory volume was observed, whereas, less abdominal pain, less diarrhea, and a reduction of systemic corticosteroids were seen in patients with intestinal acute GvHD. Conclusions: ECP might not only abrogate symptoms but also reduce mortality caused by complications from high-dose steroid treatment. Taken together, ECP offers a serious treatment avenue for patients with steroid-refractory intestinal acute GvHD and BOS. Full article
(This article belongs to the Special Issue Novel Prophylactic and Therapeutic Strategies for Acute Graft versus Host Disease)
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17 pages, 2711 KiB  
Article
Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement
by Nikolett Lupsa, Ákos Szegedi, András Gézsi, Zoltán Vuncs, Tamás Masszi, Gábor Mikala, Péter Reményi, Sara Deola, Arun Prasath Lakshmanan, Annalisa Terranegra, Edit I. Buzás and Zoltán Pós
Biomedicines 2022, 10(3), 519; https://doi.org/10.3390/biomedicines10030519 - 22 Feb 2022
Cited by 1 | Viewed by 2385
Abstract
Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and [...] Read more.
Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two established markers of skin- and gut aGvHD. The discovery cohort (n = 39) revealed that at the time of diagnosis, plasma KRT20 showed a progressive decrease from unaffected individuals to patients with single-, and patients with multi-organ aGvHD. KRT20 was affected by cutaneous (p = 0.0263) and gastrointestinal aGvHD (p = 0.0242) independently and in an additive manner. Sensitivity and specificity of KRT20 for aGvHD involving both target organs (AUC = 0.852) were comparable to that of PI3 for skin-aGvHD (AUC = 0.708) or that of REG3A for gut-aGvHD (AUC = 0.855). Patient follow-up in the validation cohort (n = 67) corroborated these observations (p < 0.001), and linked low KRT20 to grade 2+ disease (p < 0.001), but failed to confirm low KRT20 as an independent risk factor. These data established a link between low plasma KRT20 levels and moderate to severe aGvHD involving multiple target organs. Full article
(This article belongs to the Special Issue Novel Prophylactic and Therapeutic Strategies for Acute Graft versus Host Disease)
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Review

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26 pages, 1481 KiB  
Review
Effect of Vitamin D on Graft-versus-Host Disease
by Alfonso Rodríguez-Gil, Estrella Carrillo-Cruz, Cristina Marrero-Cepeda, Guillermo Rodríguez and José A. Pérez-Simón
Biomedicines 2022, 10(5), 987; https://doi.org/10.3390/biomedicines10050987 - 24 Apr 2022
Cited by 7 | Viewed by 3492
Abstract
The different cell subsets of the immune system express the vitamin D receptor (VDR). Through the VDR, vitamin D exerts different functions that influence immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies explored the impacts of [...] Read more.
The different cell subsets of the immune system express the vitamin D receptor (VDR). Through the VDR, vitamin D exerts different functions that influence immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies explored the impacts of vitamin D levels on the outcomes of patients undergoing allogeneic hematopoietic stem-cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results were confirmed in a prospective cohort trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies was also explored. Considering this dual effect on both the immune systems and tumor cells of patients with hematologic malignancies, vitamin D might be useful in this setting to decrease both graft-versus-host disease and relapse rates. Full article
(This article belongs to the Special Issue Novel Prophylactic and Therapeutic Strategies for Acute Graft versus Host Disease)
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16 pages, 640 KiB  
Review
The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease
by Jarosław Biliński, Marcin Jasiński and Grzegorz W. Basak
Biomedicines 2022, 10(4), 837; https://doi.org/10.3390/biomedicines10040837 - 1 Apr 2022
Cited by 18 | Viewed by 4661
Abstract
The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but [...] Read more.
The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40–60% of patients will respond to the therapy and some others will be steroid-dependent. There is still no consensus regarding the best second-line option, but fecal microbiota transplantation (FMT) has shown encouraging preliminary and first clinically relevant results in recent years and seems to offer great hope for patients. The reason for treatment of steroid-resistant acute GvHD using this method derives from studies showing the significant immunomodulatory role played by the intestinal microbiota in the pathogenesis of GvHD. Depletion of commensal microbes is accountable for aggravation of the disease and is associated with decreased overall survival. In this review, we present the pathogenesis of GvHD, with special focus on the special role of the gut microbiota and its crosstalk with immune cells. Moreover, we show the results of studies and case reports to date regarding the use of FMT in the treatment of steroid-resistant acute GvHD. Full article
(This article belongs to the Special Issue Novel Prophylactic and Therapeutic Strategies for Acute Graft versus Host Disease)
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