Comparison of alemtuzumab and ATG-based conditioning in adult recipients of allogeneic hematopoietic cell transplantation (HCT) for severe aplastic anemia: A retrospective study
Notice bibliographique
Résumé
Abstract Background The optimal in-vivo T-cell depleting agent for allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia (SAA) remains unclear. Current guidelines endorse the use of either rabbit anti-thymocyte globulin (ATG) or alemtuzumab, with selection guided by institutional experience and availability. We aimed to compare clinical outcomes in adults with acquired SAA undergoing HCT from matched sibling (MSD) or unrelated donors (MUD) using either ATG-based conditioning or a historical cohort treated with alemtuzumab-based regimens. Methods A retrospective analysis of patients with acquired SAA who underwent HCT at our center between May 2010 and 2024 was conducted. The ATG-based regimen consisted of intravenous (IV) fludarabine 30 mg/m²/day from day −5 to −2, cyclophosphamide 60 mg/kg/day on days −5 and −4, and rabbit anti-thymocyte globulin (Thymoglobulin) at a total dose of 4.5 mg/kg, administered over days -3 to -1. The alemtuzumab-based regimen included identical doses of fludarabine and cyclophosphamide, with alemtuzumab at a total dose of 60 mg, administered over days−8 to −4. For patients receiving MUD grafts, low-dose total body irradiation (TBI) at 200 cGy was added on day −1. Results A total of 62 patients (median age: 30 years (IQR: 25 – 48) underwent HCT during the study period. MSD were used in 34 patients (55%). Alemtuzumab-based conditioning was used in 20 patients (32%), while the remaining received ATG. Median follow-up of the entire cohort was 59 months (range: 48–72), significantly longer in the alemtuzumab group [134 months (99–156) vs. 47 months (21–49), p<0.01]. Bone marrow (BM) grafts were used in 39 patients (63%), with a higher proportion in the alemtuzumab group (81% vs. 53%, p=0.02). The median nucleated cell dose was 3.3 (2.2–3.9) ×10⁸/kg for BM grafts, and 7 (5 – 8) x 106/kg for peripheral blood stem cell grafts, and was similar between groups. Median time to neutrophil engraftment was 19 days (range: 16–32) with alemtuzumab and 17 days (15–21) with ATG (p=0.34). Platelet engraftment occurred earlier in the alemtuzumab group (median 12 days vs. 20 days with ATG, p=0.03). Complete donor chimerism at day +30 was observed in 42 patients, with no difference between the groups. Primary graft failure occurred in 10 patients, including 6 in the alemtuzumab group. The cumulative incidence of primary graft failure was 13% (95% CI: 3–31) with alemtuzumab and 8% (95% CI: 2–19) with ATG (p=0.12). At day +100, rates of acute grade II–IV graft versus host disease (aGvHD) were 23% with alemtuzumab and 15% with ATG (p=0.63); grade III–IV aGvHD occurred in 9% vs. 1%, respectively (p=0.27). At two years, the incidence of chronic GvHD (all grades) was 4.5% (1–19) with alemtuzumab and 14% (5–27) with ATG (p=0.57). Eight patients died during follow-up: 2 from primary graft failure, 1 from aGvHD, and 5 from infections, with no significant differences in causes of death between the two groups. Three-year event-free survival (EFS) was 64% (40–78) and 70% (53–83), and overall survival (OS) was 91% (68–97) and 85% (68–93) in the alemtuzumab and ATG groups, respectively (p=0.59 and p=0.43). On multivariable analysis, alemtuzumab use was associated with faster platelet engraftment, with no significant impact on rates of acute or chronic GvHD, primary graft failure, EFS, or OS. Conclusion Alemtuzumab-based conditioning was associated with faster platelet engraftment compared to ATG, with comparable rates of graft failure, GvHD, EFS, and OS between the two groups. Our study suggests that either agent is a reasonable option, with choice guided by availability and institutional experience.
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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 | 0,000 | 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 ».