Improved Survival in Red Blood Cell Transfusion Dependent Patients with Primary Myelofibrosis (PMF) Receiving Iron Chelation Therapy.
Notice bibliographique
Résumé
Abstract Patients (pts) with PMF and iron overload (IOL) may receive iron chelation therapy (ICT), although there are no data demonstrating that this improves clinical outcome. Red blood cell (RBC) transfusion dependent (TD) pts with thalassemia receiving ICT have improved survival and decreased end-organ toxicities and RBC-TD pts with myelodysplastic syndrome (MDS) receiving ICT have improved survival. We performed a review of 41 pts seen from January 1987 to April 2007 with a bone marrow biopsy confirmed diagnosis (Dx) of PMF. Clinical data were collected from the practice database, the Provincial Home Hemosiderosis Program of British Columbia database, and by chart review. Pts receiving ICT were treated with desferrioxamine (DFO) 0.5–3g by subcutaneous infusion over 12 hours, 35 days per week or with deferasirox (DFX) 20mg/kg/day orally, dose adjusted to response and pt tolerance. 29 were male and 12 female. Median age at PMF Dx was 64 (43–86) years (y) and 24 pts were >60y. White blood cell (WBC) count at Dx was <4 or >30x109/L in 8, hemoglobin (Hgb) <100 G/L in 5, platelet count <100x109/L in 5, monocyte count >1x109/L in 7. Karyotype analysis was: normal, n=16; del(6)(q25), n=1; tri(14), str12p, n=1; complex, n=1. Lille, Strasser and Mayo prognostic scores were: low risk, n=15, 8, 11; intermediate, n=15, 19, 9; high, n=5, 11, 5 respectively. Primary PMF treatment was: supportive care, n=23; hydroxyurea, n=10; immunomodulatory, n=4; splenectomy, n=2. Clinical evidence of IOL was documented in 21 pts; number of RBC units (NRBCU) received, n=18; ferritin >2000ug/l, n=6 (and ferritin >1000ug/l, n=1); CHF, n=5; liver disease, n=3; endocrine, n=3. 16 pts were RBC transfusion–independent (TI) and 25 were TD; of these 10 received ICT. Median duration of ICT was 18.3 (0.1–117) months (mo) and reasons for initiating ICT were: NRBCU received, n=9; elevated ferritin, n=6; clinical evidence of IOL, n=3. Five pts received DFO, 4 DFX, and 1 DFO followed by DFX. In ICT pts, initial/Pre-ICT ferritin levels were significantly higher than in TD-NO ICT pts at a median of 2318 (range 263–8400) and 527 (120–934) mg/L respectively (p=0.05) and decreased significantly in TD-ICT pts at most recent follow-up to 1571 (1005–3211) mg/L (p=0.01). Causes of death were: TI patients, no deaths; TD-NO ICT patients, 11 deaths (73%): probably PMF-related, n=9; progression to PMF-blast phase (BP), n=3; sepsis, n=3; cardiac, n=2; bleeding, n=1, unknown, n=2 ; TD-ICT patients, 2 deaths (20%); PMF-BP, n=1; bleeding, n=1. Kaplan- Meier analysis showed a median overall survival (OS) for all pts of 126.5 (14.4–293.2) mo. In a univariate analysis of TD pts, factors significant for OS (and 5y OS) were: WBC count at Dx (4.0–30x109/L, 69%; <4.0 or >30x109/L, 0%; p=0.002); monocyte count at Dx (<1.0x109/L, 74%; >1.0x109/L, 0%; p=0.0001); Mayo prognostic score (low, 67%; intermediate, 50%; high, 0%; p=0.05); NRBCU transfused (<20U, 30%; 21–50U, 27%; >50U, 12%; p=0.02) and receiving ICT (ICT, 89%; NO-ICT, 34%; p=0.003). In Cox regression analysis of TD pts, factors significant for OS were: NRBCU (p=0.001) and ICT (p=0.0001). For TI, TD-NO ICT and TD-ICT pts respectively the median OS was not reached (NR) at 200 mo, 58 mo and NR at 293 mo respectively (p=0.01 for TD-NO ICT vs TI and NS for TD-ICT vs. TI). The hazard ratio (HR) for pts receiving >20 RBCU was increased at 7.6 (95% CI 1.2–49.3) and the HR for pts receiving ICT was improved at 0.15 (0.03–0.77). In conclusion, 61% of PMF pts developed RBC-TD and had inferior OS, however TD pts receiving ICT had superior OS compared to TD pts not receiving ICT and the OS of TD-ICT pts was comparable to the OS of TI patients, suggesting a benefit to ICT. These are to our knowledge the first data documenting improved clinical outcome in pts with PMF receiving ICT. Prospective studies of IOL and the impact of ICT in pts with PMF are warranted.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 | 0,001 |
| 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 ».