A Randomized Pilot Trial Comparing Anti-Thymocyte Globulin (ATG) with ATG Plus Post Transplant Cyclophosphamide (PTCy) for Prophylaxis Against Acute and Chronic Graft Versus Host Disease (GVHD) in Matched Donor Hematopoietic Cell Transplants (HCT)
Bibliographic record
Abstract
Background: Anti-thymocyte globulin (ATG, or ATLG) and post-transplant cyclophosphamide (PTCy) are used for the prevention of graft-versus-host disease (GVHD). Two ongoing randomized trials (ISRCTN50290131; NCT05153226) are comparing these agents for efficacy and safety, but the safety and efficacy of the combination is unknown and has not been well studied. We conducted a randomized pilot trial of a combination of these agents to assess safety, with the aim of an expansion phase III trial. Methods: Following CONSORT guidelines, we conducted a randomized pilot trial to compare ATG (standard Arm A, 4.5 mg/kg) with ATG plus PTCy (experimental Arm BE, ATG 4.5 mg/kg, PTCy 50 mg/kg x 2) with short term feasibility endpoints at 100 days but otherwise following a phase III design. Patients consented to two years follow-up in anticipation of an expansion to phase III, as described in the CONSORT extension for pilot trials (Abbade LPF et al (2018) DOI 10.1186/s40409-018-0142-2). Overall survival was calculated using the Kaplan-Meier estimate; the log-rank test was used to compare treatment differences. We randomized a pre-planned convenience sample of 79 eligible and transplanted patients. Median (range) age was 59 (19 to 74), 47 (59.5 %) were male. Patients had either AML (n=55) or MDS (n=24) and were transplanted using either myeloablative (n=49) or reduced intensity (n=30) conditioning. Donors, either sibling (n=28) or unrelated (n=51), were 8/8 HLA-matched. The primary feasibility endpoints included: (1) recruitment of the intended sample size, (2) 100-day survival of the experimental arm B to be at least 90% compared with the standard arm A, (3) complete data on 95% of recipients at 12 months and (4) completion of the trial within budget. A variety of secondary endpoints, both efficacy and safety, were included. Objectives 1, 3, and 4 were fulfilled and this abstract describes the safety and efficacy outcomes related to objective (2). Results at day 100: Forty-one patients were randomized to Arm A and thirty-eight patients to Arm BE. At the time of data lock (May 14, 2024), all patients had been followed for at least 100 days. Thirty-nine (95.1%) patients in Arm A and 36 (94.7%) in Arm B survived to 100 days (primary endpoint). Acute graft versus host disease (AGVHD) was reported in 15 and 6 patients in Arms A and BE respectively, of which 6 and 3 had grades II-IV and 3 and 0 had grades III-IV. At 100 days, 3 patients in Arm A and 3 patients in Arm BE were receiving systemic corticosteroids. Serious Adverse Effects (SAEs) were experienced by 31 patients in Arm A and 25 in Arm BE. Graft failure at 28 days occurred in 2 patients in each arm, with all patients achieving engraftment eventually. Median (range) days to engraftment was 19 (13-45) for Arm A and 22.5 (15-56) for Arm BE. Cytomegalovirus reactivations occurred in 10 and 7 patients in Arm A and Arm BE respectively and Epstein-Barr virus reactivations occurred in 7 and 4 patients in Arm A and Arm BE respectively. Results Follow Up: Median follow up of living patients was 23.6 months (range 3.19- 25.92) for Arm A patients and 22.9 months (range 1.64-25.07). Overall survival between the arms was similar at 12-months; 68.9% (standard error (SE) 7.5%) in the standard arm A and 75.4% (SE 7.6%) in the experimental arm BE (p = 0.52). Relapse or disease progression were seen in 7 patients in Arm A and 7 patients in Arm BE. AGVHD was reported in 18 patients in Arm A and 9 in Arm BE (grades II-IV 11 and 5, grades III-IV 5 and 1), with late (>100 days) AGVHD occurring in 3 and 2 cases in Arms A and BE respectively. CGVHD has been reported to date in 7 patients in Arm A and 4 patients in Arm BE, moderate or severe grade in 2 patients and 2 patients respectively. Conclusion: The addition of PTCy to ATG did not result in excessive adverse events in this pilot trial (to day 100), and long-term results remained consistent. The combination of ATG and PTCy can be used safely in future trials to further prevent graft-versus-host disease. Based on the demonstrated safety and feasibility of this combination, and encouraging signals of efficacy, planning for an expansion to a full phase III trial with a primary endpoint of GVHD, relapse free survival is underway.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.007 | 0.007 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
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".