Non-Myeloablative Matched Sibling Allo-HCT for Adults with Sickle Cell Disease in Canada.
Notice bibliographique
Résumé
Background There is growing experience with allo-HCT as a curative therapy for adults with sickle cell disease (SCD). Non-myeloablative (NMA) HCT from a matched sibling donor (MSD) appears to be an effective and relatively non-toxic option. Here we report the first Canadian experience with MSD HCT after NMA conditioning in adults with SCD. Methods A retrospective chart review study at two Canadian transplant centres was undertaken at Princess Margaret Cancer Centre in Toronto (PM) and Tom Baker Cancer Centre in Calgary (TBC). Included were consecutive adult patients receiving PBSCs from a MSD after NMA conditioning with alemtuzumab and a single fraction of 3 Gy TBI as described in Hsieh et al. JAMA. 2014;312. Alemtuzumab was administered IV in 6 and subcutaneously (SC) in 3 patients at PM and SC in all patients at TBCC. At TBC, grafts were infused fresh vs cryopreserved at PM. Results 15 patients are included (9 at PM/6 at TBC). HCT was for HbSS in 9/9 at PM and 5/6 at TBC (1 HbSC). Most patients had >1 indication for HCT: recurrent VOC was the most common. Median age was 30 at PM (range 20-48) and 36 at TBC (24-47). Median cell dose was 8.9 × 10 6 CD34/kg at PM (range 7.6-22.1) and 8.8 at TBC (4.6-20.4). Alemtuzumab had less adverse effects with SC vs IV administration. No graft failure occurred. At PM and TBC, 2 and 1 patients did not experience neutrophils <0.5 × 10 9 /L. In the remainder, neutrophil engraftment occurred at a median of 22 (range 14-24) and 19 days (17-22), respectively. At PM and TBC, respectively, 5 and 3 patients did not experience platelet nadir <50 × 10 9 /L. At PM, 1 patient experienced grade 1 aGVHD and 1 had mild cGVHD. At TBC, no aGVHD and 1 had mild cGVHD. At PM and TBC, respectively, 4 and 0 patients were treated for CMV reactivation. No patient required treatment for EBV reactivation. One-year post-HCT chimerism in T- and myeloid cells was available for 7 patients at PM (T-cells: median 47.9% donor, range 29-60.6%, myeloid cells: median 97.8%, range 82-98.1) and 4 at TBC (T-cells: median 56% donor, range 50-78%, myeloid cells: 100% in all). The trajectory of T-cell chimerism at each site is shown in figure 1. All patients are alive, engrafted and without recurrent SCD or subsequent neoplasm at a median of 516 (range 28-1396) and 1391 (91-2499) days post-HCT at PM and TBC, respectively. Of the 6 and 4 patients >1-year post-HCT at PM and TBC, respectively, 2 and 4 have been tapered off sirolimus at a median of 839 and 506 days, respectively. Three patients with available chimerism at 63-301 days after sirolimus stop had T- and myeloid chimerism 62.9-66% and 94.8-100% donor, respectively, with no decrease observed after sirolimus stop. Conclusions Early Canadian experience with NMA matched sibling allo-HCT for SCD suggests it is a safe and effective curative therapy for SCD. SC alemtuzumab is effective with less side-effects compared to IV administration. Favourable outcomes are seen with both cryopreserved and fresh grafts.
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 | 0,001 |
| Études des sciences et des technologies | 0,002 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».