Cytomegalovirus Infections Following Reduced-Intensity Allogeneic Stem Cell Transplantation.
Bibliographic record
Abstract
Abstract Reduced intensity allogeneic stem cell transplantation is increasingly used for patients who are at high risk for mortality following conventional full-intensity regimens. Defining the risk of CMV-related events in this growing modality has a significant implication in future immunologic interventions to improve their transplant outcomes. Therefore, we analyzed 160 patients at risk for CMV (R+ and/or D+) who received a reduced intensity transplant (RIT) between May 2000 and February 2004 from either a matched-related (n=91) or unrelaed donor (n=69) under the City of Hope IRB protocol #02047. The median age of the cohort was 51 (range: 15–71) and recipient/donor CMV serostatus was; R+D+=87, R+D-=44, R-D+=29. Conditioning regimens were reduced but myeloablative (fludarabine + melphalan or busulfan) in 124 or truly non-myeloablative (TBI 200cGy +/− fludarabine) in 36 patients. Fourteen received a bone marrow graft and the remaining 146 received PBSC graft. GVHD prophylaxis consisted of cyclosporine and mycophenolate +/− short course of methotrexate. CMV reactivation was monitored by shell vial blood culture (BC) twice a week from d21 until d100 or longer if clinically indicated. Additional monitoring with quantitative PCR was available in 57 patients. Preemptive therapy with ganciclovir was started at the first positive BC at 5mg/kg twice a day for a week, followed by maintenance therapy for 5 weeks. Of 160 patients, at the time of analysis 94 patients are alive with a median follow up of 12.2 months. The actuarial probabilities of overall survival, disease-free survival, and relapse for the entire cohort at 1 year were 55.9 %, (95%CI: 51.1–60.5), 40.4% (95% CI: 37.1–43.7), and 40.1% (95%CI: 34.8–46.2), respectively. Grade 2–4 acute GVHD occurred in 91 (56%) patients. Eighty-one patients developed CMV reactivation (actuarial probability of 52+/−4%) at the median of 44 days post-transplant (range: d20-d216, 8 after d100). Of these, 42 (52%) had either persistent or recurrent reactivation. Nineteen patients (12%) developed CMV disease (8 with pneumonitis, 11 with GI tract) at the median onset of 56 days (range d28-d591: 5 after d100). Seven of these 19 patients had both BC and PCR data, which were consistent each other in all but one. CMV viremia itself did not predict poorer survival (p=NS), but CMV disease was associated with lower overall survival (37% vs. 65%, p=0.02). The univariate analysis revealed two major findings: 1) CMV seropositive patients were at seven times the ‘hazard’ (HR: 7.2, 95%CI: 2.3–22.9) for CMV reactivation compared to those who were CMV seronegative (p<0.001); and 2) patients who received a true non-myeloablative regimen were at decreased ‘risk’ for CMV reactivation compared to those who received fludarabine + melphalan or busulfan (HR: 0.42, 95%CI: 0.2–0.8) (p<0.01). In multivariate analysis these factors remained significant. In summary, our data demonstrate the significant incidence of CMV reactivation and disease in RIT, but true non-myeloablative transplants may have lower risk. Future immunologic or pharmacologic interventions should include RIT patients.
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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) | 0.001 | 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".