High Post-Transplant Ferritin Level Associates with Adverse Survival and Higher Mortality Rate following Allogeneic Hematopoietic Stem Cell Transplant, whereas Pre-Transplant Ferritin Level Does Not
Notice bibliographique
Résumé
Abstract Background: Allogeneic hematopoietic stem cell transplantation (HCT) is a curative therapy for many hematologic and non-hematologic diseases; however, it is associated with significant morbidity and mortality. Many studies have shown that elevated pre-transplant ferritin levels are associated with increased risk of morbidity and mortality following HCT. Given ferritin's association with systemic inflammation, it is a plausible potential prognostic marker in the post-HCT period, including in patients with graft-versus-host disease (GVHD). The present study attempts to determine whether post-transplant serum ferritin level is an independent prognostic marker for outcomes post-HCT, especially in the subgroups of patients with acute or chronic GVHD. Methods and patients: A total of 229 patients who had serum ferritin level data available within one-year post HCT were enrolled into this retrospective study. These patients underwent HCT at Princess Margaret Cancer Centre, Toronto, Canada between 2001-2013. Patients' characteristics and transplant procedures were: median age: 51 (range:19-70); refined disease risk index: low (n=70), intermediate (n=108), high (n=51); donor type: HLA-matched related donors (n=94), HLA-matched or partially-matched unrelated donors (n=135); conditioning regimen: myeloablative (n=120), reduced intensity (n=109). Acute and chronic GVHD were respectively classified using the 1994 consensus conference and NIH consensus criteria. Primary outcomes were overall survival (OS), non-relapse mortality (NRM), and relapse. Kaplan-Meier method was used for OS; cumulative incidences were used for NRM and relapse, considering competing risks. Multivariate analysis employed Cox or Fine-Gray proportional hazard regression model. Factors evaluated included recipient age and CMV status, donor-recipient sex, comorbidity score, performance index, GVHD prophylaxis, post-transplant serum ferritin level (ferritinPost-HCT), and serum ferritin level prior to HCT (ferritinPre-HCT). Recursive partitioning was used to stratify patients into low or high risk groups based on ferritinPost-HCT (≤3,169 vs >3,169 ng/mL) and ferritinPre-HCT (≤669 vs >669 ng/mL). Results: Median follow-up duration among survivors was 46 months post-HCT (range:2.8-147.2 months). Median ferritinPost-HCT was 2,178 ng/mL (range: 45-30,647; Figure A), measured at a median of 137 days post-HCT. There was a weak correlation between ferritinPost-HCT and ferritinPre-HCT (Pearson's correlation r=0.242, p=0.002). Compared to the group with low ferritinPost-HCT, the high ferritinPost-HCT group had lower three-year OS (40.0% vs 66.7%, p<0.001; Figure B) and higher NRM (48.6% vs 17.8%, p<0.001 Figure C), but no difference in cumulative incidence of relapse (10.5% vs 19.7%, p=0.079; Figure D). A landmark analysis was performed where the day of ferritinpost-HCT measurement was considered day 0. Results of this landmark analysis showed consistent findings: high ferritinPost-HCT showed lower three-year OS (38.3% vs 65.4%; p<0.001) and higher NRM (50.6% vs 17.7%; p<0.001) compared to low ferritinPost-HCT, but no difference in relapse (10.7% vs 21.3%, p=0.077). In multivariate analysis, ferritinPost-HCT was found to be an independent prognostic factor for OS (p=0.001, HR 2.323) and NRM (p<0.001, HR 3.905). However, pre-transplant ferritin level (ferritinPre-HCT) did not stratify well for OS (57.0% vs 61.8%, p=0.636) or NRM (30.8% vs 22.7%, p=0.247). Out of 229 patients, 171 (74.6%) developed any grade of acute GVHD, and 61 (26.6%) developed chronic GVHD. Median onset of acute and chronic GVHD were, respectively, 33.5 days and 145 days. Level of ferritinPost-HCT was significantly higher in the group that developed acute GVHD than in those without acute GVHD. However, there was no difference in ferritinPost-HCT between patients with or without chronic GVHD. FerritinPost-HCT was found to be an independent prognostic marker in the subgroup with acute GVHD for OS (p=0.001, HR 2.531) and NRM (p<0.001, HR 3.584), and in the subgroup with chronic GVHD for OS (p=0.042, HR 3.226) and NRM (p=0.009, HR 14.130). Conclusions: In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM, independent of other prognostic factors including ferritinPre-HCT or GVHD. Further prospective study including larger number of patients is warranted. Figure. Figure. Disclosures Lipton: ARIAD: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Kim:BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».