Salvage of Primary Refractory Acute Leukemia (AL) with High-Dose Etoposide (VP) and Cyclophosphamide (CY) Followed by Early Stem Cell Transplantation (SCT): An Effective Treatment Strategy for AML but Not for All.
Notice bibliographique
Résumé
Abstract Primary refractory AL has a poor prognosis although some patients (pts) can be salvaged with allogeneic SCT. Induction of complete remission (CR1) with conventional chemotherapy prior to conditioning and SCT may improve long-term event-free survival (EFS). Between 03/91 and 10/03, 59 adults with primary refractory AL (defined as >15% marrow blast cells on day 30 of induction) were treated with VP 2.4 g/m2 by 34 hr. IV infusion beginning on day 1 followed by CY 2.0 g/m2 IV daily on days 3, 4 and 5 with hyperhydration (3 L/m2/d) as bladder prophylaxis. Six pts received VP 3.0 g/m2 and 1 patient received CY 1.8 g/m2 x 4 days. The study included 39 males and 20 females with a median age of 41 years (range 17–60). Diagnoses were AML (42 pts), ALL (13 pts) and biphenotypic AL (4 pts). Eleven pts (19%) presented with a WBC count > 50 x109/L and MRC karyotype was favourable in 4 pts, intermediate in 34 pts and adverse in 20 pts; metaphase analysis failed in 1 patient. All AML pts had already received high-dose cytosine arabinoside (HIDAC) and either daunorubicin (DNR) (n=33) or mitoxantrone and VP (n=9). ALL pts had previously received DNR, vincristine and prednisone with (n=9) or without (n=4) L-asparaginase. Biphenotypic AL pts had been induced with HIDAC, DNR, vincristine and prednisone. Induction day 30 marrow blast count was > 40% in 35 pts (59%). The most common grade I/II non-hematologic toxicities of VP/CY were oral mucosal (44% of pts), GI (20% of pts) and hepatic (15% of pts); only one patient developed grade III/IV toxicity (pulmonary). Median time to recovery of ANC > 0.5 x109/L and platelets > 20 x109/L was 26 and 22 days, respectively. Three pts (5%) died prior to day 21 of VP/CY and were not evaluable for response (2 pts sepsis, 1 patient pulmonary hemorrhage). Twenty-four pts (43%) were also refractory to VP/CY but 32 pts (57%) entered CR1. Response rates were similar in AML (54%) and ALL/ABL (67%) (p=0.52) and analysis of baseline patient characteristics did not reveal any predictors of response to VP/CY. Twenty-nine of 32 CR1 pts proceeded to SCT (24 allogeneic, 5 autologous); five pts with AL refractory to VP/CY also underwent allogeneic SCT although all subsequently relapsed. Four of the autologous SCT pts relapsed with only one patient remaining alive in CR1. Estimated 5-year EFS for the entire cohort of pts is 23%. The only positive predictor of survival was male sex (p=0.03) and cytogenetic risk group did not influence outcome (p=0.69). In the allogeneic SCT group, 5-year EFS was 45% and was signficantly better for pts with AML (52%) compared to pts with ALL (14%, p=0.04). In conclusion, VP/CY is able to induce CR1 in the majority of pts with primary refractory AL. For pts with AML in CR1 that have a suitable donor, subsequent allogeneic SCT results in a favourable long-term EFS. Although pts with primary refractory ALL have a high CR1 rate with VP/CY, overall outcome for this subgroup remains poor.
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 | 0,000 |
| 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 ».