Low-Dose Antithymocyte Globulin for Graft-versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation
Bibliographic record
Abstract
Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated donor (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHCT recipients have historically had low-dose Thymoglobulin (total dose, 2.5 mg/kg; Genzyme-Sanofi, Cambridge, MA) added to our standard MRD GVHD prophylaxis regimen. In this retrospective cohort study we assessed post-HCT the effectiveness of our uniquely low-dose ATG strategy by comparing ATG exposed (MUD) and unexposed (MRD) alloHCT recipients for GVHD and other clinical HCT outcomes. This retrospective single-center study included all HCT patients transplanted for any malignant indication at The Ottawa Hospital from 2009 to 2014. MUD patients received rabbit ATG (Thymoglobulin) at a total dose of 2.5 mg/kg given over 2 days (.5 mg/kg on day –2; 2.0 mg/kg on day –1 before stem cell infusion) in addition to standard GVHD prophylaxis. Primary outcomes assessed were incidence of acute and chronic GVHD, defined as new-onset GVHD requiring systemic immunosuppressive therapy at less or more than 100 days, respectively. Secondary outcomes included disease relapse and survival. There were 110 and 77 patients in the ATG exposed (MUD) and unexposed (MRD) cohorts, respectively. At baseline there were no significant differences in median age at transplant, sex, disease indication or risk index, graft source, conditioning regimen, or intensity between cohorts. A higher proportion of 7/8 mismatched donor transplants (13% versus 3%, P = .02) and a higher median CD34 + dose (7.9 versus 4.9 × 10 8 cells; P < .01) was observed in the ATG exposed cohort. No differences were noted in platelet engraftment. ATG exposed patients had significantly shorter time to neutrophil engraftment than the unexposed cohort (16 versus 19 days, respectively; P < .01). ATG exposed patients had significantly lower rates of GVHD than ATG unexposed patients (57% versus 79%; P = .01), with differences predominantly in rates of chronic GVHD (18% versus 44%, P < .01). At median follow-up of 28 (range, 3 to 69) and 25 (range, 2 to 73) months for survivors in ATG exposed and unexposed cohorts, respectively, no significant differences in overall survival (median overall survival not met for either cohort), relapse incidence (26% versus 29%, P = .73), or relapse-free survival (RFS) (not met in ATG exposed and 26 months in ATG unexposed, P = .22) were observed between groups. The ATG exposed cohort had significantly higher GVHD-free RFS (GRFS) with a 2-year GRFS of 23% versus 3% ( P = .003). There were no significant differences between cohorts in proportion of patientswith post-HCT infectious episodes or intensive care unit admissions. Here we report significantly lower rates of chronic GVHD and significant improvement in GRFS in an ATG exposed MUD alloHCT cohort compared with an ATG unexposed MRD cohort. These findings were observed without differences in relapse, survival, infectious complications, or intensive care unit admissions. Our findings highlight the association of unconventionally low-dose ATG with improved GVHD outcomes and suggest a need for prospective study of ATG use in lower doses.
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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) | 0.005 | 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".