Incidence of Anicteric Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) and Efficacy of Defibrotide (DF) in Patients Post-HSCT in an Expanded-Access Program
Bibliographic record
Abstract
IntroductionHepatic VOD/SOS is a progressive, potentially life-threatening complication of HSCT or nontransplant chemotherapy. VOD/SOS diagnosis by Baltimore criteria requires bilirubin >2 mg/dL; hyperbilirubinemia is not required by modified Seattle criteria, and may be a late finding in the progression of VOD/SOS. DF is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the US and Canada, and to treat severe hepatic VOD/SOS post-HSCT in patients (pts) aged >1 month in the EU. This post hoc analysis examines incidence of VOD/SOS without elevated bilirubin, and survival in DF-treated, post-HSCT pts in the expanded-access T-IND program (2007–2016).MethodsThe T-IND enrolled pts with VOD/SOS diagnosed per Baltimore or modified Seattle criteria. Patients received DF 25 mg/kg/day, recommended for ≥21 days.ResultsOf 991 post-HSCT pts with recorded bilirubin at diagnosis, 190 (19%) had bilirubin <2 mg/dL (Table). Of these, 133 were aged ≤16 years (24% of the 564 post-HSCT pediatric pts), and 57 were aged >16 years (13% of the 427 post-HSCT adults).Across all 1000 post-HSCT pts in the T-IND (including 9 without baseline bilirubin data), Kaplan-Meier estimated Day +100 survival (Figure) was 58.9% (95% CI, 55.7%–61.9%). In the overall population of pts with bilirubin <2 mg/dL, 61.1% and 18.4% of pts had ≥1 treatment emergent AE (TEAE) and ≥1 treatment related AE (TRAE), respectively, and 21.1% had ≥1 hemorrhage event; for pts with bilirubin ≥2 mg/dL: 73.8% had ≥1 TEAE, 21.7% had ≥1 TRAEs, and 31.1% had ≥1 hemorrhage event.ConclusionsIn the T-IND, 19% of post-HSCT pts with VOD/SOS had bilirubin <2 mg/dL at diagnosis (24% of children; 13% of adults). Accordingly, 190 pts would not have been diagnosed if hyperbilirubinemia was a required criterion. Of pts with bilirubin <2 mg/dL, 80% of pediatric pts and 49% of adults were diagnosed with VOD/SOS ≤21 days post-HSCT, showing that anicteric VOD/SOS can develop within 21 days post-HSCT in a considerable number of pediatric and adult pts. These results confirm that pediatric pts may not have hyperbilirubinemia, which is no longer mandatory for EBMT pediatric criteria, and further clearly show that anicteric VOD/SOS is also an adult phenotype. DF was associated with higher survival rate in pts with bilirubin <2 mg/dL compared with those with levels ≥2 mg/dL. These results compare favorably with the overall study findings, suggesting that treatment before the onset of hyperbilirubinemia may lead to better outcomes. The safety profile of the T-IND was similar to that of previous studies of DF for the treatment of VOD/SOS.SupportJazz Pharmaceuticals.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".