Mycophenolate Compared to Methotrexate As Part of Cyclosporine Based-GVHD Prophylaxis Does Not Affect Transplant Outcomes, Reduces Organ Specific Acute And Chronic GVHD, but Increases The Risk of CMV Viremia In Matched Related Donor Peripheral Blood Stem Cell Transplantation
Bibliographic record
Abstract
Abstract Introduction Graft versus host disease (GVHD) remains the most frequent and serious complication following allogeneic hematopoietic stem cell transplantation (HSCT). There is marked variability in GVHD prophylaxis regimens but the most commonly used is methotrexate (MTX) in combination with cyclosporine (CSA). However MTX toxicity can mandate dose reductions resulting in an increased risk of acute GVHD (aGVHD). There is limited and conflicting data on the efficacy of mycophenolate (MMF) in comparison to MTX. Methods and patients We retrospectively reviewed 242 consecutive patients who received related donor myeloablative peripheral blood stem cell transplantation between 2002 and 2012 at the Princess Margaret Cancer Centre, Toronto Canada. We compared patients who received MMF/CSA (n=71) (institutional standard of care since 2009), to a historical control who received MTX/CSA (n=171). MTX was given IV as 15 mg/m2 on day +1, and 10 mg/m2 on days +3, +6, and +11 post HSCT with adjustments made for mucositis, renal and liver dysfunction and effusions. MMF was given as 45mg/kg/day in 3 divided doses orally from day 0 to +30 post HSCT. In both GVHD prophylaxis regimens the CSA strategy was the same (5 mg/kg/day IV q12h starting day -1 aiming for therapeutic trough levels between 200-400 mcg/L). Routine surveillance of CMV viremia was performed using pp65 antigenemia (>1 positive cell) until 2011 and thereafter this was performed using PCR (>200 copies). There were no differences in patient characteristics except for age and conditioning regimens due to period effect and institutional changes in practice. Results There was no difference between the MTX/CSA and MMF/CSA groups in 3-year overall survival (66.1% vs 56.9%, p=0.09), 3-year non-relapse mortality (19.0% vs 27.4%, p=0.13) and relapse (15.5% vs 16.0%, p=0.56). Patients in the MMF/CSA group had significantly faster neutrophil and platelet engraftments: medians of 13 vs 18 days and 10 vs 14 days respectively (p<0.001). The cumulative incidence of aGVHD (grades 2-4) was significantly higher in the MTX/CSA group 74.4% vs 45.1% (p<0.001). There was no difference in the incidence of gut aGVHD but there was a higher incidence of skin (71.5% vs 51.5% p<0.001) and liver (53.0% vs 11.3% p<0.001) aGVHD in the MTX/CSA vs MMF/CSA groups. There was no difference between the two groups in the 5-year cumulative incidence of chronic GVHD (cGVHD) or gastrointestinal, liver or skin cGVHD. There was however, a significantly lower incidence of lung, eye and mouth cGVHD in the MTX/CSA group: 29% vs 46.8% (p=0.04) for lung cGVHD, 37.7% vs 71.5% (p<0.001) for eye cGVHD and 59.6% vs 72.8% (p=0.001) for mouth cGVHD. The incidence of CMV reactivation was significantly lower in the MTX/CSA group, 40.9% vs 58.1% (p<0.001) in the MMF/CSA group. In multivariate analysis MMF/CSA was identified as an independent favorable factor for aGVHD (p=0.001, HR 0.62) but as a significant risk factor for CMV reactivation (p=0.005, HR 1.94). Conclusion The use of MMF/CSA in MRD PBSC transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA. MMF/CSA is associated with faster engraftment but a higher risk of CMV reactivation. Disclosures: Off Label Use: Mycophenoplate compared to methotrexate as part of cyclosporine based graft versus host disease prophylaxis.
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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 | 0.001 |
| 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) | 0.002 | 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".