CMV Reactivation Pre and Post Letermovir Prophylaxis, a Single Centre Review of Clinical Outcomes and Resource Utilization
Bibliographic record
Abstract
Introduction Prospective, randomized trials have demonstrated reduction in the incidence of clinically significant CMV infections (csCMVi) with use of letermovir prophylaxis (LP) in allogeneic hematopoietic stem cell transplant (alloHSCT). Publicly funded LP became available at our cent for routine use in late . We evaluated clinical and health resource utilization outcomes in patients at high risk of csCMVi before and after implementation of LP to assess its impact. Methods We retrospectively analyzed alloHSCT recipients at high risk of CMV (as defined by Marty et al, NEJM 2017) at our center during two time periods. The Pre-LET group underwent HSCT between January 1, 2019, and December 31, 2020 and not receive LP, while the Post-LET group underwent HSCT between and received LP. The patients who were deemed to be at high risk of CMV reactivation were CMV seropositive recipients: 1) with a mismatched or haploidentical donor, or an umbilical cord blood graft, 2) treated with ATG conditioning, 3) required high-dose steroids or ATG for acute graft versus host disease (GVHD), or 4) with documented history of CMV disease prior to HSCT. LP was initiated on day +10 provided baseline (day +7) if CMV DNA was undetectable (< 35 IU/mL) and continued until day +100. Those with detectable CMV DNA (>35 IU/mL) at baseline were excluded from the study as they did not qualify for publicly funded LP at our center. Pre-emptive therapy (PET) for CMV reactivation was initiated when viral titers were >1000 IU/mL, if not on LP, o and >500 IU/mL, if on LP. We collected data pertaining to the baseline characteristics, transplant details and clinical outcomes of the study subjects, using our electronic databases. We examined CMV related outcomes for the first year from the transplant. Results: We identified 155 patients (Pre-LET 98, Post-LET 57). The mean age was 49 year (range 19-72) and 53 years (21-71) in the Pre-LET and Post-LET groups respectively (p=0.068). The most common diagnosis in either group was acute myeloid leukemia (Pre- 46%, Post- 37%). Most patients received myeloablative conditioning (79% in both groups). ATG was often included for GVHD prophylaxis (Pre- 88%, Post- 81%, p=0.22). Grade 2-4 acute GVHD was seen in 46/98 (46.9%) of Pre-LET patients and 20/57 (35.1%) of Post-LET patients. Fifty-five of 98 (56.1%) Pre-LET patients needed ³1mg/kg of corticosteroids for GVHD treatment, compared to 23/57 (40.4%) the Post-LET patients (p=0.058). csCMVi . 4/9 Post-LET patients had csCMVi while taking LP; three had acute GVHD at the time and one was receiving >1mg/kg corticosteroids. The Post-LET group had 83% reduction in odds of needing PET compared to Pre-LET (p<0.001). Time to initiation of PET from transplant was significantly longer in Post-LET group (152d vs 42d, p=0.001). Valgancyclovir was the most common front-line PET (Pre- 78.4%, Post- 66.7%). The duration of cumulative PET use in the first year post-transplant was longer in the Pre-LET group (24.0 days/person-year vs 6.7 days/person-year, p <0.001). There was no significant difference in the rate (Pre- 9.2%, Post-3.5%, p=0.19) or duration of csCMVi-related hospitalization. No death due to csCMVi or CMV disease was observed in either group. 26/98 (26.5%) Pre-LET patients required G-CSF support on PET, in contrast to 2/57 (3.5%). Post-LET patients (p<0.001). There was no difference in risk of relapse or overall survival between the Pre-LET and Post-LET groups (Estimated 1-year RFS 0.78 vs. 0.72; estimated 1-year OS 0.81 vs. 0.88). Conclusions Our data provide unique insight into the change in clinical outcomes of patients at high risk of csCMVi after publicly funded LP became available. LP was associated with lower incidence of csCMVi, PET use and G-CSF requirement. There was no significant difference in hospitalization or survival between the groups. Our real-world data is in concordance with the findings from previously published studies, demonstrating utility of LP in reducing the burden of disease of csCMVi. Further research into blood product utilization and patient related quality of life outcomes would be of interest.
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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 | 0.006 | 0.027 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.007 | 0.011 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".