Favorable Outcomes with Low Dose Anti Thymocyte Globulin Based Graft Versus Host Disease Prophylaxis after Mismatched Unrelated Donor Allogenic Hematopoietic Cell Transplantation
Bibliographic record
Abstract
Anti-thymocyte globulin (ATG) based Graft versus Host disease (GVHD) prophylaxis is widely used for unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Registry-based and single-center retrospective analyses have suggested superior outcomes with PTCy-based GVHD prophylaxis regimens when compared to ATG-based in mismatched unrelated donor (MMUD) allogeneic HCT. However, these studies used doses of ATG ≥ 5mg/kg. Outcomes following MMUD allogeneic HCT with lower dose ATG-based GVHD prophylaxis regimens have not been extensively studied. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG-based regimens at our centre. All adult patients undergoing standard of care allogeneic HCT at The Ottawa Hospital from January 2015 to December 2022 were included. Data regarding demographics, HLA mismatched allele, conditioning regimen, dose of ATG, time to engraftment, and rates of acute and chronic GVHD were collected. Primary outcomes were overall survival (OS) and secondary outcomes included GVHD-free relapse-free survival (GRFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). Survival outcomes were analyzed using Kaplan-Meier analysis. Predictors of survival were identified using the Cox-proportional hazards regression model. Seventy-seven (n=77) patients (Males 62.3% (n=48); Median (range) age 50 (18-70) years) underwent allogeneic HCT from MMUD. Most frequently mismatched locus was HLA A in 37.7% (n= 29) followed by HLA B in 14.3% (n=11). Myeloablative conditioning regimen was received by 76.6% (n=59) while reduced intensity regimens were used in 23.4% (n=18) patients. Rabbit ATG was used in all patients with the majority (81%; n=63) receiving 2.5mg/kg and the remaining 18.2% (n=14) receiving 4.5mg/kg of ATG. Grade II-IV acute GVHD occurred in 24.7% (n=19) while chronic GVHD occurred in 32.5% (n= 25) patients. After a median follow-up of 21 months, relapse occurred in 28.6% of patients. Two-year OS(Fig 1) and GRFS (Fig 2) were 60.6% and 45.3% respectively. Dose of ATG (2.5 mg/kg vs 4.5 mg/kg) was not a predictor of outcomes in either univariate and multivariate analyses. When compared to published single-center and registry-based studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG seems to provide improved outcomes in patients undergoing MMUD allogeneic HCT (Table 1). Our findings suggest that lower dose ATG-based GVHD prophylaxis regimens may provide outcomes comparable to PTCy-based regimens in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy-based regimens to determine ideal GVHD prophylaxis for these 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 | 0.001 | 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".