Favourable Impact on Acute and Chronic Graft-Versus-Host Disease with Cyclophosphamide and In-Vivo Anti-CD52 Monoclonal Antibodies for Marrow Transplantation from HLA-Identical Sibling Donors for Acquired Aplastic Anaemia.
Notice bibliographique
Résumé
Abstract Despite excellent long-term results of bone marrow transplantation (BMT) in acquired severe aplastic anemia (SAA), graft-versus-host disease (GVHD) continues to remain a major concern. Approximately 30–40% patients experience chronic GVHD resulting in long-term complications and impaired quality of life. At St. George’s Hospital, we investigated the role of anti-CD52 monoclonal antibodies (MoAb) in transplant protocols for SAA. The CD52 antigen is expressed widely on virtually all lymphocytes including T and B-cells, NK cells, dendritic cells, eosinophils and macrophages but is absent from erythrocytes, platelets and marrow progenitors. Between Aug 1989 and Nov 2003, 33 patients at our centre with acquired SAA underwent BMT from HLA-identical sibling donors using cyclophosphamide (CY) 50 mg/kg x 4 (days −5 to −2) and anti-CD52 MoAb 0.75–1 mg/KgBW as conditioning. Prior to 1999, rat derived anti-CD52 MoAb (Campath-1G) was used. We switched to humanized version of anti-CD52 MoAb (Alemtuzumab) when it became available in 1999. Median age at BMT was 17 yrs (range 4–46). Prior to BMT, 58% were heavily transfused (>50 transfusions) and 42% had previously failed anti-thymocyte globulin (ATG) based immunosuppressive therapy. Unmanipulated bone marrow was used as source of stem cells in all except one. GVHD prophylaxis was with cyclosporine (CSA) alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to CSA. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 (24%) patients (primary,4; secondary, 4). Graft failure was non-significantly higher in heavily transfused patients and those receiving CSA and anti-CD52 MoAb as GVHD prophylaxis. Of those failing grafts, 4 survived long-term (complete autologous recovery, 2; autotransplant from previous stored marrow, 1; second allograft, 1). Acute grade II-IV GVHD and chronic GVHD was seen in 13% and 4%, respectively. None developed extensive chronic GVHD. Of the 19 recipients positive for cytomegalovirus (CMV), reactivation was seen in 5(26%) with in 100 days. No cases of late CMV reactivation were observed. Six patients died of complications related to BMT at a median of 248 days (range 47–414). With a median follow-up of 59 months, the 5-year survival was 81% (95% C.I. 68–96). There was a non-significant trend towards improved survival in patients transplanted after 1995 (93% vs. 74%). The performance status of all survivors is 100% except one who developed avascular necrosis of hip. We conclude that the conditioning regimen containing CY and anti-CD52 MoAb is well tolerated and efficacious for acquired SAA using HLA-matched sibling donors. The long-term survival with this conditioning appears to be equivalent to current standard conditioning for acquired AA (CY and ATG) and the impact on acute and chronic GVHD is particularly notable. Based on the results of our study we are further investigating the role of Alemtuzumab in the transplant protocols for AA using CSA alone as GVHD prophylaxis.
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) | 0,002 | 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 ».