New perspectives on the use of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation and graft‐versus‐host disease
Open accessAbstract
Inhibition of the mechanistic target of rapamycin (mTOR) has been exploited largely both in solid tumour oncology and solid organ transplantation. More recently mTOR inhibitors such as sirolimus and everolimus have been introduced to the field of allogeneic haematopoietic stem cell transplantation where their unique combination of immunosuppressive purposes offering reduced nephrotoxicity and potential antimalignant effects reflect a unique drug profile that has led to their widespread use in both prophylaxis and therapy of graft‐versus‐host disease (GVHD). On the other hand haematological insufficiency, infectious complications as well as vasculopathies, have been frequently reported as limiting toxicities. Here, we review both the retrospective and prospective experience available to date and stress the need for prospective registration trials to reduce off label use and improve patient safety by optimizing dosing and enhancing pharmacovigilance. Furthermore, we speculate on the future role of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation.
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Rapamycin has been extensively utilized for transplant rejection prophylaxis and graft-versus-host disease, as well as seizure control and reduction of tumors in tuberous sclerosis complex patients.
“Rapamycin has been extensively utilized for transplant rejection prophylaxis and graft-versus-host disease, as well as seizure control and reduction of tumors in tuberous sclerosis complex patients [499–501].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [500]
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Saade, A., Styczyński, J., & Cesaro, S. (2020) · Journal of Infection · doi:10.1016/j.jinf.2020.06.009 · Cited by 27 · see citing works
Ehx, G., Ritacco, C., Hannon, M., Dubois, S., Delens, L., Willems, É., Servais, S., Drion, P. V., Beguin, Y. P., & Baron, F. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16505 · Cited by 24 · see citing works
Tijaro-Ovalle, N. M., Karantanos, T., Wang, H.-T., & Boussiotis, V. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00295 · Cited by 24 · see citing works
Metabolic Pathways in Alloreactive T Cells
Brown, R., & Byersdorfer, C. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01517 · Cited by 17 · see citing works
Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling
Wang, Z., Xu, Z., Zong, M., & Fan, L. (2025) · Metabolism Open · doi:10.1016/j.metop.2025.100369 · Cited by 18 · see citing works
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Medical Aspects of mTOR Inhibition in Kidney Transplantation
Cuadrado-Payán, E., Diekmann, F., & Cucchiari, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147707 · Cited by 14 · see citing works
Exosomes, MDSCs and Tregs: A new frontier for GVHD prevention and treatment
Hess, N. J., Kink, J. A., & Hematti, P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1143381 · Cited by 13 · see citing works
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T-Cell Metabolism in Graft Versus Host Disease
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Age-related modifications of macrophages influenced by “inflammageing” in graft vs. host disease
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Chronic graft-versus-host disease: focusing on the B cells
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Hematopoietic Stem Cell Transplantation in Patients with Inborn Errors of Immunity and Malignancy
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Melnikov, M. E., Дробинцева, А. О., Savelieva, O. E., Lyapunova, L. S., Кондратьев, Г. В., & Kulyova, S. A. (2026) · Advances in molecular oncology · doi:10.17650/2313-805x-2026-13-2-37-48
- Authors
- Lutz, M., & Mielke, S.
- Affiliations
- University of Münster (DE)
- University of Würzburg (DE)
- Corresponding author
- Mielke, Stephan
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2016-06-22
- Volume
- 82
- Issue
- 5
- Pages
- 1171-1179
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC5061796
- OpenAlex
- W2418028176
- Cited by
- 32
- References
- 76
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 2
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- mTOR inhibitors, rapamycin, everolimus, allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, immunosuppression, nephrotoxicity, infectious complications, vasculopathy, pharmacovigilance, off-label drug use, dose optimization
- MeSH terms
- Graft vs Host Disease, Humans, Immunosuppressive Agents, Hematopoietic Stem Cell Transplantation, TOR Serine-Threonine Kinases
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