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

Research output: Contribution to journalArticlepeer-review

Authors

  • A. N. Parker
  • K. S. Peggs
  • C. M. Harvey
  • S. Natarajan
  • D. I. Marks
  • B. Jackson
  • G. Chakupurakal
  • M. Dennis
  • Z. Lim
  • G. Cook
  • B. Carpenter
  • A. R. Pettitt
  • S. Mathew
  • L. Connelly-Smith
  • J. A. L. Yin
  • R. Chakraverty
  • K. Orchard
  • B. E. Shaw
  • J. L. Byrne
  • Sridhar Chaganti

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 less than or equal to10 000 and less than or equal to40 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.

Details

Original languageEnglish
Pages (from-to)280-286
Number of pages7
JournalBone Marrow Transplantation
Volume49
Early online date11 Nov 2013
Publication statusPublished - 2014

Keywords

  • alemtuzumab dli ebv immunotherapy ptld sct bone-marrow-transplantation high-risk preemptive rituximab disease reconstitution lymphoma reactivation lymphocytes prevention management