Dose, Schedule and PK Practices with IV Busulfan-Based Conditioning Regimens in a Non-Inferiority Study: Heterogenous Practices But Low VOD and TRM
Bibliographic record
Abstract
The CIBMTR is conducting a non-inferiority study of myeloablative IV busulfan-based conditioning regimens vs. traditional ablative cyclophosphamide and TBI in patients (pts) with myeloid malignancies undergoing related or unrelated SCT to compare overall survival between regimens. Accrual is complete with 477 pts conditioned with CyTBI and 1273 with IV busulfan-based regimens from 120 centers. We report initial data regarding busulfan (BU) dosing and PK practices. Of 1273 pts receiving IV BU, the regimen was ablative in 1118 and reduced intensity in 155. Donors were related (507 pts) or unrelated (766 pts). Diagnosis was AML (791 pts), MDS (365 pts), CML (117 pts). Graft source was BM (272 pts) or PB (1001 pts). Median age was 47 (1-61) yrs and 52% of pts were male. The majority (66%) had a performance score of 90-100. GVHD prophylaxis for all pts was a calcineurin inhibitor of tacrolimus (1035 pts) or cyclosporine (238 pts) +/- other agents. BU dosing was most commonly Q6H followed by daily. The vast majority of pts received 4 days of BU (95%), including about half of the RIC group. Approximately half of both related and unrelated SCT recipients underwent PK testing. Most PK testing was done with the first dose of conditioning (80.6%), the remainder as a preceding test dose. Dose adjustment was planned for nearly all pts receiving ablative regimens that underwent PK testing (98%) and in a minority of RIC pts (8%). BU was targeted based on AUC in 63.5%; the remainder with CSS. Some centers used both AUC and CSS for PK testing. Most pts' subsequent BU dose (77.6%) was adjusted in response to PK results including 5 RIC pts. The incidence of VOD at 100 days for all pts receiving IV busulfan-based conditioning was 5% (4%-7%) and was similar in pts receiving ablative or RIC. In 889 pts with data available, the cumulative incidence of TRM at 100 days and 6 months was 8% (6%-10%) and 12% (10%-14%). Practices regarding BU dosing and schedules and the use of PK testing with IV busulfan-based conditioning vary within and between centers. In a large prospective observational study, IV busulfan-based conditioning regimens appear safe with a low incidence of VOD and TRM in a group of pts receiving both related and unrelated transplants. Results from the comparative study after 1 year of follow up will address the safety and efficacy of IV busulfan-based conditioning regimens compared to CyTBI.
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 | 0.018 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".