Treosulfan- Versus Busulfan-based Conditioning in Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Single-center Retrospective Propensity Score-matched Cohort Study
Bibliographic record
Abstract
Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia (CMML) at Princess Margaret Hospital, Toronto 2015-2022. Using propensity score matching, we compared transplant outcomes between two well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n=46) or fludarabine-busulfan with total body irradiation (FBT200) (n=92). A scoring system based on patient age, Karnofsky performance score and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m2) or high-dose (42 g/m2) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the two groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P=0.61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-vs-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) and anti-thymocyte globulin (ATG) . Patients who received FT had a superior 2-y overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1-81.2) vs. 44.5% (95% CI: 34-54.4), hazards ratio (HR): 0.43, 95% CI: 0.22-0.84 (P=0.013). In multivariate analysis (MVA), only the use of fresh grafts (P=0.02) and FT (P=0.01) were associated with improved OS. FT was associated with superior 2-y relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6-77.9) vs. 39.1% (95% CI: 29.1-49.1), HR: 0.44 (95% CI: 0.24-0.81), P=0.008. In MVA, the use of fresh grafts (P=0.03) and FT (P=0.009) were associated with improved RFS. Recipients of FT demonstrated superior 2-y graft versus host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8-72.8) vs. 35.1% (95% CI: 25.5-45). In MVA, only FT was associated with superior GRFS (P=0.02). FT recipients exhibited markedly superior 1-y event-free survival (EFS) compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9-54.2) vs. 9.2% (95% CI: 4.4-16.3), HR: 0.47 (95%CI: 0.30-0.72), P<0.001) and MVA (P=0.004). FT was associated with lower 1-y non-relapse mortality (NRM) compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0-21.8) vs. 29.7% (95% CI: 20.6-39.3), HR: 0.41 (95% CI: 0.17-0.96), P=0.04) and MVA (P=0.04). Our study utilized propensity score matching to demonstrate superiority of treosulfan- over busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfan-based conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m2.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".