Early CMV Reactivation Still Remains a Cause of Increased Transplant Related Mortality in the Current Era: A CIBMTR Analysis
Notice bibliographique
Résumé
Abstract Introduction: Since the early days of allogeneic hematopoietic cell transplantation (HCT), positive serology for cytomegalovirus (CMV) in either the recipient or the donor, and CMV reactivation have been associated with poorer outcomes. In the 90’s, development of effective monitoring and potent antiviral drugs minimized and occasionally abrogated this negative impact. Recently, some studies have reported an unexpected association between early CMV reactivation and decreased incidence of relapse in AML. The Center for International Blood and Marrow Research (CIBMTR) sought to conduct a retrospective large scale study to reassess the impact of CMV serology and CMV reactivation in the current era. Methods: The analysis includes comprehensive data of 11,153 patients undergoing first allogeneic HCT between 2003 and 2010 reported to the CIBMTR. Separate analyses were conducted for each of the 6 patient categories: AML transplanted with bone marrow (BM) or peripheral blood stem cell (PBSC) (n=5310), AML transplanted with cord blood (CB) (n= 925), ALL with BM/PBSC (n=1883), ALL with CB (n= 759), CML with BM/PBSC (n=1079) and MDS with BM/PBSC (n=1197). CMV serology from the donor (D) or recipient (R), and reactivation of CMV (as a time-dependent co-variate) within the first year after HCT were analyzed as risk factors for outcomes. The median duration of follow up was 56 months (1 – 127 months). Results: The median time to CMV reactivation was 40 days (1 – 362 days) after HCT and 98% of reactivations occurred before day 100 (D+/R+ 32%, D+/R- 11%, D-/R+ 34%, D-/R- 4%). In multivariable analysis, throughout the 6 groups, a positive serology (D+/R+, D+/R-, D-/R+) vs a negative serology (D-/R-),had no effect on the risk of GVHD (acute or chronic) or the risk of relapse, except for an increased risk of chronic GVHD for BM/PBSC recipients with ALL. CMV positive serology was associated with a higher transplant related mortality (TRM) and a poorer overall survival (OS). For a R+ patient, a D- compared to a D+, had no negative impact except for ALL with BM/PBSC where a D- was associated with a poorer OS. After PBSC/BM transplantation, CMV reactivation was associated with a higher TRM for MDS (RR=1.61, p=0.0002), CML (RR=1.86, p=0.0004), AML (RR=1.68; p<0.0001) and ALL (RR=1.95; p<0.0001), translating into lower OS (range of RR from 1.27 to 1.49; p value from 0.003 to <0.0001). Only among AML patients following CB transplantation, CMV reactivation did not worsen OS. Moreover, CMV reactivation had no effect on the incidence of relapse irrespective of the diagnosis or the source of stem cells. Finally, we conducted a subset analysis focusing on the group of AML, transplanted with PBSC after a myeloablative conditioning regimen and with a GVH prophylaxis relying on Ciclosporine and Methotrexate only. In multivariable analysis, there was no difference in the risk of relapse based on CMV reactivation as a time-dependent co-variate [RR 0.96 (0.65 – 1.4), p=0.8385]. Conclusion: Positive D/R CMV serology still results in increased TRM and decreased OS after HSCT in the current era. Early CMV reactivation did not prevent relapse in patients with AML, MDS, CML or ALL after HCT. Disclosures Boeckh: Chimerix: Consultancy, Research Funding; Viropharma: Research Funding; Genentech/Roche: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Clinigen: Consultancy.
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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 | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| 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 ».