Faculty Collaboration Database

EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant 2014 Feb;49(2):280-6

Date

11/12/2013

Pubmed ID

24212561

DOI

10.1038/bmt.2013.170

Scopus ID

2-s2.0-84893769793 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50-65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had 10 000 and 40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12-0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.

Author List

Fox CP, Burns D, Parker AN, Peggs KS, Harvey CM, Natarajan S, Marks DI, Jackson B, Chakupurakal G, Dennis M, Lim Z, Cook G, Carpenter B, Pettitt AR, Mathew S, Connelly-Smith L, Yin JA, Viskaduraki M, Chakraverty R, Orchard K, Shaw BE, Byrne JL, Brookes C, Craddock CF, Chaganti S

Author

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Antibodies, Monoclonal, Murine-Derived
Antineoplastic Agents
Cohort Studies
Epstein-Barr Virus Infections
Female
Hematopoietic Stem Cell Transplantation
Humans
Immunotherapy
Lymphoproliferative Disorders
Male
Middle Aged
Prognosis
Retrospective Studies
Rituximab
Survival Analysis
Transplantation Conditioning
Viral Load