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Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial
Open accessAbstract
Background Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial.Methods We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00779194.Findings Between March 9, 2009, and Dec 8, 2014, 43 patients were enrolled, three of whom did not meet eligibility criteria. 11 of the 40 eligible patients discontinued study treatment because of intolerance (n=2) or non-compliance (n=9). SLEDAI and BILAG disease activity scores were reduced during 12 months of treatment in 16 (55%) of 29 patients who completed treatment. Mean SLEDAI score decreased from 10·2 (SD 5·6) at enrolment to 4·8 (4·5) after 12 months of treatment (p<0·001) and the mean total BILAG index score decreased from 28·4 (12·4) at enrolment to 17·4 (10·7) after 12 months of treatment (p<0·001). The mean daily dose of prednisone required to control disease activity decreased from 23·7 mg (SD 9·6) to 7·2 mg (2·3; p<0·001) after 12 months of treatment. Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. CD8+ memory T cells were selectively expanded in SRI-responders. Patient liver function and lymphocyte counts were unchanged. Although HDL-cholesterol (Z=-2·50, p=0·012), neutrophil counts (Z=-1·92, p=0·054), and haemoglobin (Z=-2·83, p=0·005) were moderately reduced during treatment, all changes occurred within a range that was considered safe. Platelet counts were slightly elevated during treatment (Z=2·06, p=0·0400).Interpretation These data show that a progressive improvement in disease activity is associated with correction of pro-inflammatory T-cell lineage specification in patients with active systemic lupus erythematosus during 12 months of sirolimus treatment. Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus.Funding Pfizer, the National Institutes of Health, and the Central New York Community Foundation.
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“Additionally, mTOR blockade in patients with SLE treated with N-acetylcysteine or rapamycin reduces both pro-inflammatory T cells and disease activity85,260, suggesting that dietary supplementation or drugs that regulate mitochondrial dynamics might constitute novel therapeutic avenues for mitigating autoantibody production in SLE.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [260]
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Cites
The 1982 revised criteria for the classification of systemic lupus erythematosus
Tan, E. M., Cohen, A. S., Fries, J. F., Masi, A. T., Mcshane, D. J., Rothfield, N. F., Schaller, J. G., Talal, N., & Winchester, R. J. (1982) · Arthritis & Rheumatism · doi:10.1002/art.1780251101 · Cited by 14,519
Hochberg, M. C. (1997) · Arthritis & Rheumatism · doi:10.1002/art.1780400928 · Cited by 11,409
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846
Derivation of the sledai. A disease activity index for lupus patients
Bombardier, C., Gladman, D. D., Urowitz, M. B., Caron, D., Chang, C. H., Austin, A., Bell, A., Bloch, D. A., Corey, P. N., Decker, J. L., et al. (1992) · Arthritis & Rheumatism · doi:10.1002/art.1780350606 · Cited by 4,570
Tsokos, G. C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-37754-6.50094-4 · Cited by 3,990
Tsokos, G. C. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100359 · Cited by 2,814
Navarra, S., Guzmán, R., Gallacher, A., Hall, S., Levy, R. A., Jimenez, R., Li, E. K., Thomas, M., Kim, H., Leon, M. G., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61354-2 · Cited by 2,078
Vézina, C., KUDELSKI, A., & Sehgal, S. N. (1975) · The Journal of Antibiotics · doi:10.7164/antibiotics.28.721 · Cited by 1,691
Using MetaboAnalyst 3.0 for Comprehensive Metabolomics Data Analysis
Xia, J., & Wishart, D. S. (2016) · Current Protocols in Bioinformatics · doi:10.1002/cpbi.11 · Cited by 1,560
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509
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Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2020) · Cell Research · doi:10.1038/s41422-020-0291-z · Cited by 590
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Angajala, A., Lim, S., Phillips, J. B., Kim, J. H., Yates, C. C., You, Z., & Tan, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01605 · Cited by 469
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Zhou, M., Xu, W., Wang, J., Yan, J., Shi, Y., Zhang, C., Ge, W., Wu, J. S., Du, P., & Chen, Y. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.08.035 · Cited by 360
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Sharabi, A., Tsokos, M., Ding, Y., Malek, T. R., Klatzmann, D., & Tsokos, G. C. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.148 · Cited by 301
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Sharabi, A., & Tsokos, G. C. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0356-x · Cited by 300
Choi, S.-C., Brown, J., Gong, M., Ge, Y., Zadeh, M., Li, W., Croker, B. P., Michailidis, G., Garrett, T. J., Mohamadzadeh, M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax2220 · Cited by 266
Dai, X., Fan, Y., & Zhao, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02168-0 · Cited by 280
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Shan, J., Jin, H. H., & Xu, Y. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01027 · Cited by 224
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Noguchi, M., Hirata, N., Tanaka, T., Suizu, F., Nakajima, H., & Chiorini, J. A. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2724-5 · Cited by 223
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Li, H., Boulougoura, A., Endo, Y., & Tsokos, G. C. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102870 · Cited by 211
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Ursini, F., Russo, E., Pellino, G., D’Angelo, S., Chiaravalloti, A., Sarro, G. D., Manfredini, R., & GIORGIO, R. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01236 · Cited by 197
Yap, D. Y. H., & Chan, T. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246231 · Cited by 195
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Wang, L., Liang, Y., Zhao, C., Ma, P., Zeng, S., Ju, D., Zhao, M., Yu, M., & Shi, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02326-4 · Cited by 190
Wang, Z., Zhou, H., Zheng, H., Zhou, X., Shen, G., Teng, X., Liu, X., Zhang, J., Wei, X., Hu, Z., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1725381 · Cited by 168
Wen, Z., Jin, K., Shen, Y., Yang, Z., Li, Y., Wu, B., Tian, L., Shoor, S., Roche, N. E., Goronzy, J. J., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0296-7 · Cited by 162
Huang, N., Chi, H., & Qiao, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01023 · Cited by 174
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Yin, H., Wu, H., Chen, Y., Zhang, J., Zheng, M., Chen, G., Li, L., & Lu, Q. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01512 · Cited by 156
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Choi, S., Titov, A. A., Abboud, G., Seay, H. R., Brusko, T. M., Roopenian, D. C., Salek‐Ardakani, S., & Morel, L. M. (2018) · Nature Communications · doi:10.1038/s41467-018-06686-0 · Cited by 153
The immunobiology of mTOR in autoimmunity
Suto, T., & Karonitsch, T. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102373 · Cited by 149
Fajgenbaum, D. C., Langan, R.-A., Japp, A. S., Partridge, H. L., Pierson, S. K., Singh, A., Arenas, D. J., Ruth, J. R., Nabel, C. S., Stone, K., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126091 · Cited by 147
Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine
Ibrahim, H., Perl, A., Smith, D. E., Lewis, T. C., Kon, Z. N., Goldenberg, R., Yarta, K., Staniloae, C. S., & Williams, M. R. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108544 · Cited by 151
Self-citationInhibition of Glycolysis Reduces Disease Severity in an Autoimmune Model of Rheumatoid Arthritis
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Wei, X., Luo, L., & Chen, J.-Z. (2019) · Cells · doi:10.3390/cells8091075 · Cited by 136
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Condello, M., Pellegrini, E., Caraglia, M., & Meschini, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030725 · Cited by 117
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Raza, I. G. A., & Clarke, A. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681105 · Cited by 105
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Zhou, S., Klionsky, D. J., & Zhang, H. (2019) · Autophagy · doi:10.1080/15548627.2019.1580512 · Cited by 105
Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated
Wu, C., Fu, Q., Guo, Q., Chen, S., Goswami, S., Sun, S., Li, T., Cao, X., Chu, F., Chen, Z., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215039 · Cited by 104
Double-negative T cells in autoimmune diseases
Li, H., & Tsokos, G. C. (2020) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000778 · Cited by 105
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Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells
Li, H., Adamopoulos, I. E., Moulton, V. R., Stillman, I. E., Herbert, Z. T., Moon, J. J., Sharabi, A., Krishfield, S., Tsokos, M., & Tsokos, G. C. (2020) · Nature Communications · doi:10.1038/s41467-020-16636-4 · Cited by 104
Li, W., Deng, C., Yang, H., & Wang, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00159 · Cited by 102
Splicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity
Katsuyama, T., Li, H., Comte, D., Tsokos, G. C., & Moulton, V. R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127949 · Cited by 96
From Systemic Inflammation to Neuroinflammation: The Case of Neurolupus
Bendorius, M., Po, C., Muller, S., & Jeltsch‐David, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113588 · Cited by 97
Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases
Kingsmore, K. M., Grammer, A. C., & Lipsky, P. E. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0337-0 · Cited by 97
Fortner, K. A., Blanco, L. P., Buskiewicz, I. A., Huang, N., Gibson, P. C., Cook, D. L., Pedersen, H. L., Yuen, P. S. T., Murphy, M. P., Perl, A., et al. (2020) · Lupus Science & Medicine · doi:10.1136/lupus-2020-000387 · Cited by 94
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Koga, T., Sato, T., Furukawa, K., Morimoto, S., Endo, Y., Umeda, M., Sumiyoshi, R., Fukui, S., Kawashiri, S., Iwamoto, N., et al. (2018) · Arthritis & Rheumatology · doi:10.1002/art.40785 · Cited by 89
Omarjee, L., Janin, A., Perrot, F., Laviolle, B., Meilhac, O., & Mahé, G. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108464 · Cited by 91
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Chen, P.-M., Katsuyama, E., Satyam, A., Li, H., Rubio, J., Jung, S., Andrzejewski, S., Becherer, J. D., Tsokos, M., Abdi, R., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo4271 · Cited by 86
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Khunsriraksakul, C., Li, Q., Markus, H., Patrick, M. T., Sauteraud, R., McGuire, D., Wang, X., Wang, C., Wang, L., Chen, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36306-5 · Cited by 79
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Blagosklonny, M. V. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1822-8 · Cited by 74
Sun, F., Wang, H. J., Liu, Z., Geng, S., Wang, H. T., Wang, X., Li, T., Morel, L. M., Wan, W., Lu, L., et al. (2020) · The Lancet Rheumatology · doi:10.1016/s2665-9913(20)30004-7 · Cited by 73
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Tenbrock, K., & Rauen, T. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109031 · Cited by 72
Grzes, K. M., Sanin, D. E., Kabat, A. M., Stanczak, M. A., Edwards-Hicks, J., Matsushita, M., Hackl, A., Hässler, F., Knoke, K., Zahalka, S., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.10.009 · Cited by 70
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Yap, D. Y. H., Tang, C. S.-O., Chan, G. C. W., Kwan, L. P. Y., Ma, M. K. M., Mok, M. M. Y., & Chan, T. M. (2018) · The Journal of Rheumatology · doi:10.3899/jrheum.180507 · Cited by 70
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Boehncke, W., & Brembilla, N. C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01198 · Cited by 68
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Patiño‐Martínez, E., & Kaplan, M. J. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01267-0 · Cited by 72
Murayama, G., Chiba, A., Kuga, T., Makiyama, A., Yamaji, K., Tamura, N., & Miyake, S. (2020) · Rheumatology · doi:10.1093/rheumatology/keaa060 · Cited by 67
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Spihlman, A. P., Gadi, N., Wu, S., & Moulton, V. R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.589474 · Cited by 65
Autophagy and immunological aberrations in systemic lupus erythematosus
Qi, Y., Zhou, S., & Zhang, H. (2019) · European Journal of Immunology · doi:10.1002/eji.201847679 · Cited by 67
Advances in systemic lupus erythematosus pathogenesis via mTOR signaling pathway
He, J., Ma, J., Ren, B., & Liu, A. (2019) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2019.09.022 · Cited by 69
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Qin, Y., Gao, C., & Luo, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.828191 · Cited by 68
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Xu, Y., Chen, Y., Zhang, X., Ma, J., Liu, Y., Cui, L., & Wang, F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.920029 · Cited by 64
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Koga, T., Ichinose, K., Kawakami, A., & Tsokos, G. C. (2019) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2019.1593141 · Cited by 60
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Wang, T., Jiao, Y., & Zhang, X. (2020) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-020-08821-6 · Cited by 61
Koga, T., Ichinose, K., Kawakami, A., & Tsokos, G. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.624971 · Cited by 62
Tsai, C., Shen, C., Liao, H., Li, K., Lee, H.-T., Lu, C.-S., Wu, C.-H., Kuo, Y., Hsieh, S., & Yu, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163878 · Cited by 58
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Li, Q., Marcoux, G., Hu, Y., Rebetz, J., Guo, L., Semple, E., Provan, D., Xu, S., Hou, M., Peng, J., et al. (2024) · Autoimmunity Reviews · doi:10.1016/j.autrev.2024.103677 · Cited by 56
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Ji, L., Xie, W., & Zhang, Z. (2020) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2020.07.006 · Cited by 53
Metadata
- Authors
- Lai, Z.-W., Kelly, R., Winans, T., Marchena, I., Shadakshari, A., Yu, J., Dawood, M., Garcia, R., Tily, H., Francis, L., Faraone, S. V., Phillips, P. E., & Perl, A.
- Affiliations
- SUNY Upstate Medical University (US)
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 391
- Issue
- 10126
- Pages
- 1186-1196
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC5891154
- OpenAlex
- W2791734424
- Cited by
- 412
- References
- 43
- Citations by year
- 2026: 35 · 2025: 43 · 2024: 51 · 2023: 35 · 2022: 67 · 2021: 44 · 2020: 56 · 2019: 49 · 2018: 31
- FWCI
- 38.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- Syracuse University
- National Institute of Allergy and Infectious Diseases (R01AI048079, R01AI122176, R56AI048079, R01AI072648, R34AI141304)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- rapamycin, systemic lupus erythematosus, mTOR inhibition, T cell dysfunction, refractory lupus, disease activity, BILAG index, SLEDAI, drug safety and tolerability, biomarker-driven treatment, mTOR inhibitors, immunosuppressive therapy, dose adjustment, adverse events, lupus nephritis, proteinuria, thrombocytopenia
- MeSH terms
- Adolescent, Adult, Aged, Drug Tolerance, Female, Humans, Immunosuppressive Agents, Lupus Erythematosus, Systemic, Male, Middle Aged, Prospective Studies, Treatment Outcome, Sirolimus, Young Adult
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