Superior Survival of Myeloablative over Reduced-Intensity Conditioning in MDS Patients below 65 Years Using a Combination of Antithymocyte Globulin and Post-Transplantation Cyclophosphamide As Gvhd Prophylaxis
Bibliographic record
Abstract
Background: Allogeneic hematopoietic cell transplantation (Allo-HCT) is a potentially curative treatment for patients with myelodysplastic syndrome (MDS), particularly those classified as high-risk. The choice of conditioning regimen remains contentious, with previous studies indicating that overall survival (OS) is similar between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC), although RIC is associated with lower transplant-related mortality (TRM) and higher relapse rates. This study aims to evaluate the outcomes of MAC versus RIC in patients undergoing Allo-HCT for MDS, with a unified graft-versus-host disease (GVHD) prophylaxis regimen comprising a combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). Methods: We performed a retrospective analysis of 80 MDS patients who underwent Allo-HCT at Princess Margaret Cancer Centre between October 2015 and October 2023. Patients were under the age of 65 years and received the same GVHD prophylaxis with a combination of ATG, PTCy, and cyclosporine. Outcomes assessed included overall survival (OS), relapse-free survival (RFS), GVHD-free/RFS (GRFS), acute and chronic GVHD, and graft failure. Results: Among our cohort, 59 patients received RIC (Fludarabine 35 mg/m²/day for 4 days + Busulfan 3.2 mg/kg/day for 2 days + TBI 200, Fludarabine 35 mg/m²/day for 4 days + Treosulfan 10 or 14 g/m² for 3 days) and 21 patients received MAC (Fludarabine 35 mg/m²/day for 4 days + Busulfan 3.2 mg/kg/day for 4 days). The median age was significantly lower in the MAC group than in the RIC group (52 years vs. 60 years) (p<0.001). Matched unrelated donors (MUD) constituted the majority of the donor pool (52.5%), with no significant difference between the RIC and MAC groups (p=0.25). The RIC group had a higher proportion of patients with a hematopoietic cell transplant comorbidity index (HCT-CI) ≥3 (44.1% vs. 14.3%, p=0.02). The 1-year OS was significantly higher in the MAC group than in the RIC group (85.7% vs. 52.0%, p=0.03). The 1-year non-relapse mortality (NRM) did not significantly differ between the RIC and MAC groups (20.4% vs. 14.3%, p=0.47). The 1-year relapse rate was higher in the RIC group than in the MAC group (28.9% vs. 9.5%, p=0.05). The incidence of acute GVHD grade I-IV at day 100 was higher in the MAC group but did not reach statistical significance (52.4% vs. 39.0%, p=0.19). There were no significant differences observed between MAC and RIC in the incidence of acute GVHD grade II-IV (23.8% vs. 27.1%, p=0.85) or grade III-IV (9.5% vs. 6.8%, p=0.61), respectively. However, the incidence of chronic GVHD at 1 year was significantly higher in the MAC group compared to the RIC group (36.8% vs. 5.7%, p<0.001). Our analysis also indicated a trend of superiority in the 1-year GRFS in the MAC group compared to the RIC group (61.9% vs. 43.9%, p=0.17). Regarding the risk of graft failure, there was no significant difference in the incidence of graft failure between the comparative groups (p=0.22). Looking at infectious complications post-HCT, there was no significant difference in the incidence of bloodstream infection (BSI) between the MAC group and the RIC group (61.9% vs. 50.8%, p=0.52). Additionally, the risk of CMV reactivation did not statistically differ between the groups (p=0.12). Conclusion: Our findings suggest that MAC may offer better overall survival and relapse-free survival in patients under 65 years undergoing stem cell transplantation with ATG-PTCy-CSA, despite a higher incidence of chronic GVHD. The lack of significant differences in non-relapse mortality between conditioning regimens highlights the need for individualized patient assessment when selecting the appropriate conditioning regimen.
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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".