Limited Efficacy of Prompt Therapy of Posttransplant Lymphoproliferative Disorder (PTLD) with Rituximab
Notice bibliographique
Résumé
Abstract Introduction: Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) incidence is particularly high when using graft versus host disease (GVHD) prophylaxis with rabbit antithymocyte globulin (ATG). Preemptive therapy with rituximab given when EBV DNAemia exceeds a threshold has been adopted by some centers. However, this exposes a large fraction of patients to rituximab, which is costly and toxic (neutropenia). Wagner et al suggested a high efficacy of prompt therapy (monitoring EBV DNAemia, having a high index of suspicion for PTLD in patients with high DNAemia, and treating PTLD with rituximab at a presumed early stage)(Blood 103:3979, 2004). In Alberta, we adopted the prompt therapy in 2012. Here we report our experience. Methods: We retrospectively studied 511 patients undergoing myeloablative allogenic hematopoietic stem cell transplant (HCT). ATG (4.5 mg/kg) was used for GVHD prophylaxis in addition to methotrexate and cyclosporine. Between 1/2007 and 1/2011, no EBV monitoring was done and PTLD (usually histologically diagnosed, including Epstein-Barr encoding RNA [EBER] in situ hybridization) was treated with rituximab (period "No EBV Monitoring", 267 patients). Between 2/2011 and 4/2012, EBV monitoring (weekly till day 100) was done, but PTLD was treated with rituximab only when histologically diagnosed ("Transition" period, 88 patients). We noted that histologically proven PTLD occurred only with EBV DNAemia >40,000 genome copies/mL blood. Between 5/2012 and 12/2014, EBV monitoring was done, PTLD was diagnosed as clinical/radiological manifestation of PTLD with EBV DNAemia >40,000 and was treated with rituximab promptly (period "Prompt Therapy", 156 patients). We compared the "No EBV Monitoring" period with the "Prompt Therapy" period, using Fine-Gray analysis for cumulative incidence of PTLD, mortality due to PTLD or mortality associated with PTLD (death due to any cause after PTLD has been diagnosed) and Cox analysis for overall survival. Results: In all 3 periods combined, a total of 48 PTLDs developed at a median day 55 after HCT. 81% PTLDs occurred before day 100. Comparison of the "No EBV Monitoring" and the "Prompt Therapy" periods showed a non-significant trend toward a higher cumulative incidence of PTLD in the latter period (possibly due to the increased index of suspicion for PTLD in patients with high DNAemia), and no difference in mortality due to PTLD, mortality associated with PTLD, or overall survival (Figure 1). After rituximab, clinical/radiological regression of PTLD occurred in 15/21 (71%) patients in the No EBV Monitoring period and in 13/17 (76%) patients in the Prompt Therapy period (not significant). Next, we evaluated whether PTLD regression is associated with DNAemia becoming undetectable and progression with persistently detectable DNAemia. This was evaluated in patients from the "Transition" and the "Prompt Therapy" periods. As shown in Figure 2, all (7/7) patients with PTLD progression had persistently detectable DNAemia. Among patients with PTLD regression, DNAemia became undetectable in most (15/20) patients. 0/15 (0%) patients with persistently undetectable DNAemia developed PTLD progression, whereas 7/12 (58 %) patients with persistently detectable DNAemia developed PTLD progression. This suggests high negative predictive value but low positive predictive value of persistently detectable DNAemia for PTLD progression. Conclusion: Prompt therapy of presumed early PTLD in the setting of EBV monitoring did not result in better outcomes than therapy of presumed advanced PTLD (without EBV monitoring). Even with the prompt therapy, rituximab was only 76% efficacious. After rituximab, undetectable EBV DNAemia indicates PTLD regression, whereas persistently detectable EBV DNAemia is associated with 58% risk of PTLD progression. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
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 | 0,000 | 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) | 0,001 | 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 ».