OUTCOMES IN PATIENTS WITH B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA RECEIVING INOTUZUMAB OZOGAMICIN AND PROCEEDING TO HEMATOPOIETIC STEM CELL TRANSPLANTATION
Notice bibliographique
Résumé
Inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate indicated for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL), is associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly after post-hematopoietic stem cell transplantation (HSCT). In this sttudy, we evaluate HSCT outcomes in patients (pts) who received InO before HSCT. This observational, post-authorization safety study included pts (>=18y) in the US with B-cell precursor ALL and R/R ALL who received InO and proceeded to first allogeneic HSCT. Post-HSCT outcomes included overall survival (OS), non-relapse mortality (NRM), relapse, and adverse events (AEs). Multivariate analysis examined prognostic factors for NRM and VOD. This final analysis is based om 5-y data. 261 pts (median age 39y, 58% male) were evaluated: 36% in first complete remission (CR1), 46% in CR2, 11% in CR>=3, 4% in first relapse, 1% in >= third relapse, and 2% with primary induction failure. Prior to HSCT, 32%, 47%, 14%, 5% and <1%received 1,2,3,4, and 5 InO cycles respectively: 120 pts received InO monotherapy and 112 received InO with systemic therapy (data unavailable for 29 pts). CR/CRi and MRD negativity was achieved in 80% and 64% of pts respectively after InO> Median time from last InO dose to HSCT was 2.5 mo. Post-HSCT 18-mo OS was 54% and 50% and 18-mo NRM was 22% and 25% for pts with ALL and R/R ALL respectively; most common causes of NRM were VOD (26%, 24%) and graft-versus-host disease (GVHD: 22%, 19%). AEs<=100d post-HSCT occuring in >=30% of pts with ALL and R/R ALL respectively were bacterial infection (51%, 56%), viral infection (44%, 44%) and acute GVHD (grades II-IV; 43%, 41%). 35 pts with ALL developed VOD: 15 cases were mild, 20 were severe and 22 died <= 18 mo post-HSCT; 8/35 pts received prophylactic defibrotide (22/244 of all pts). Transplant sources for the 15 mild and 20 severe cases of VOD, respectively, were peripheral blood stem cells (n+10,12), bone marrow (n+4,8) and umbilical cord blood (n = 1,0). VOD incidence <=100d post-HSCT was, respectively: 20%, 17%, 10% and 16% in pts with cumulative InO doses of <1,8, 1.8-2.7, 2.8-3.2, and >= 3.3 mg/m2; and 15%, 2%, 17% and 14% in pts with time from las InO dose to HSCT of 1, 1.1-1.6, 1.7-4, and >=3 mo. 204 pts with ALL were included in multivariate analyses; Karnofsky score <90 or unknown (vs 90-100) and dual alkylators (compared by MAC/no dual alkylators and RIC/non-MAC) were significant negative prognostic factors for NRM at 18 mo. Dual alkylators were the only significant negative prognostic factor for VOD at 100d (compared by MAC/no dual alkylators and RIC/non-MAC). In this real-world population of adults withh ALL who received InO before HSCT, including heavily pretreated pts, 18-mo OS was 54% and 18-mo NRM was 22%. Common AEs post-HSCT were bacterial infection, viral infection, and acute GVHD. VOD incidence was consistent with previous reports and dual alkylators should be avoided, when possible, in this subset of pts. Pts receiving these regimens should be considered for clinical trials testing novel prophylactic treatments for post-HSCT endothelal dysfunction syndromes, such as VOD.
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 | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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 ».