Sirolimus as add-on therapy to corticosteroids for moderate-severe chronic graft versus host disease
Bibliographic record
Abstract
Introduction: The first-line treatment of moderate-severe chronic graft versus host disease (cGVHD) involves systemic corticosteroids ± calcineurin inhibitors. Around half of the patients will need second-line agents for corticosteroid-refractory/dependent (SR/SD) cGVHD. Herein, we report our experience using sirolimus as an add-on agent to corticosteroids in moderate-severe cGVHD. Methods: This was a single-center study of allogeneic cell transplant recipients aged ≥ 12 during 2016-2022. The diagnosis and severity of cGVHD were as per the NIH-2014 criteria. At the physician's discretion, sirolimus was added to corticosteroids for moderate to severe cGVHD. The GVHD response was classified based on the EBMT-NIH-CIBMTR criteria. Results: cGVHD occurred in 66 (49%) out of 134 recipients. It was mild in 13 (10%) and moderate-severe in 53 (39%) recipients. Sirolimus was used in 38 out of 53 (71.6%) patients with moderate-severe cGVHD, with equal proportions of matched-related (53%) and haploidentical HCT (47%) recipients. The median time to onset of cGVHD was 140 days (IQR 108-182). The onset was de novo in 14 (37%), quiescent in 15 (39%), and progressive in 9 (24%) patients. The median duration on sirolimus was 283 days (134-640). cGVHD was controlled in 30 (79%) and active in 8 (21%) recipients at 6 months. Dyslipidemia was the most common (73%) adverse event. Failure-free survival at two years was 61% (95% CI 38-78%). Discussion: This study demonstrates the safety and efficacy of sirolimus as an add-on agent to systemic corticosteroids in managing moderate-severe cGVHD. This strategy can reduce the burden of SR/SD cGVHD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".