Evidence of Effect Modification of Graft-Versus-Leukemia Effect of Cytomegalovirus By Alemtuzumab in Myeloid Malignancies Undergoing Unrelated Donor Transplantation
Bibliographic record
Abstract
Abstract Several studies have suggested a beneficial effect of CMV seropositivity and or reactivation on relapse risk after allogeneic hematopoietic cell transplantation (HCT) in myeloid malignancies. Inability to replicate this finding in T cell depleted HCT is suggestive of a potential effect modification between TCD and CMV in this setting, but this has not been addressed in previously published studies. We have retrospectively analyzed transplant outcomes in 192 patients with myeloid malignancies who have undergone unrelated donor HCT at our center during January 2006 –November 2013. Among this 111 patients received in vivo TCD with low dose (30 mg) alemtuzumab and 81 patients received non-TCD transplants. Recipients were CMV seropositive in 57% of TCD transplants and 59% of non-TCD transplants. Analysis showed a significant effect modification (p=0.03 for interaction) between alemtuzumab and CMV serostatus on relapse risk, and stratified analysis based on recipient CMV status showed inferior outcomes with alemtuzumab in CMV seropositive recipients but not in CMV seronegative recipients. In CMV seropositive recipients alemtuzumab was an independent predictor of higher relapse (Hazard Ratio=13.95, p=0.008), inferior relapse free survival (HR=2.30, p=0.002), and inferior overall survival (HR= 2.04, p=0.008). There was no difference in NRM between CMV seropositive and CMV seronegative groups, or between TCD and non-TCD transplants. These findings suggest the presence of an effect modification by TCD on CMV's effect on relapse, resulting in inferior transplant outcomes with low dose Alemtuzumab in CMV seropositive recipients, but not in seronegative recipients. Figure 1. CIR, NRM, RFS, and OS showing differential effects of T cell depletion between CMV seropositive and seronegative recipients (A-B) Cumulative incidence of relapse, (C-D) Non-relapse mortality, (E-F) Relapse free survival, and (G-H) Over all survival. Figure 1. CIR, NRM, RFS, and OS showing differential effects of T cell depletion between CMV seropositive and seronegative recipients. / (A-B) Cumulative incidence of relapse, (C-D) Non-relapse mortality, (E-F) Relapse free survival, and (G-H) Over all survival. Disclosures Off Label Use: Alemtuzumab for GVHD 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 | 0.004 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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".