Sinusoidal obstruction syndrome and other outcomes in pediatric patients with acute lymphoblastic leukemia who received inotuzumab ozogamicin before hematopoietic cell transplantation.
Notice bibliographique
Résumé
e22000 Background: Inotuzumab ozogamicin (InO) is FDA approved for adult and pediatric (≥1 y) patients (pts) with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). However, InO has been associated with increased risk of sinusoidal obstruction syndrome (SOS), particularly following hematopoietic cell transplantation (HCT). Previously reported post-HCT SOS rates are ~20% in adults and ~20–50% in pediatric pts who received InO before HCT. Methods: This observational, post-authorization safety study used data from the CIBMTR to assess post-HCT outcomes in pts with B-cell precursor ALL who received InO prior to HCT in the US. We report outcomes in pediatric pts ( < 18 y) who received InO prior to first HCT between 18 Aug 2017 and 17 Aug 2022. Results: In all, 52 pts were included (median age 9 y; 54% male; 83% with R/R ALL). Prior to HCT, 17% were in first complete remission (CR1), 40% in CR2, and 42% in CR≥3; 52%, 42%, and 6% received 1, 2, and ≥3 InO cycles, respectively; 46% received InO as monotherapy and 35% in combination with other agents (data unavailable in 19%). After InO, 39/52 (75%) achieved CR and 9/52 (17%) achieved CR with incomplete hematologic recovery; 38/47 (81%) evaluable pts were reported as minimal residual disease negative. Median (range) time from last InO dose to HCT was 1.4 (0.6–12.5) mo. Post-HCT outcomes are shown in the table. Post-HCT relapse of ALL occurred in 21 pts, of whom 7 (33%) died within 18 mo. Of 31 pts without post-HCT relapse, 6 died in remission due to SOS (n = 2), graft-versus-host disease (GVHD), organ failure, infection, or thrombotic microangiopathy (n = 1 each). In all, 16 pts developed SOS (8 mild; 8 severe). Of these, 7 received defibrotide treatment and 7 died within 18 mo (2 with SOS as cause of death). Prophylactic defibrotide was given to 23/52 pts (7/16 with SOS). Median (range) time from HCT to SOS was 10 (6–25) d. Other adverse events occurring in ≥30% of pts 100 d post HCT were viral infection (38%) and acute grade II–IV GVHD (33%). Conclusions: The rate of SOS in this real-world cohort of pediatric pts with ALL who received InO before HCT was similar to prior pediatric clinical studies. Given the high SOS rate and mortality in pediatric pts, careful consideration and pt selection should be exercised when using InO prior to HCT. Further investigation is needed to identify SOS risk factors and strategies for mitigating this risk in pediatric pts. Post-HCT outcomes. Pediatric ptsn=52 Median (range) follow-up from HCT, mo 15.2 (3.3–50.7) 12-mo overall survival % (95% CI) 71 (56–83) 6-mo transplant-related mortality, % (95% CI) 8 (2–17) 6-mo non–transplant-related mortality % (95% CI) 8 (3–17) 6-mo relapse, % (95% CI) 24 (13–37) Continued CR, n (%) 51 (98) Pts with SOS within 100 d, n 16 100-d SOS, % (95% CI) 31 (19–44) Post-SOS mortality among all pts, n (%) 7 (13)
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 | 0,001 | 0,002 |
| 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 | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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 ».