Reduced PTLD-related mortality in patients experiencing EBV infection following allo-SCT after the introduction of a protocol incorporating pre-emptive rituximab

Abstract

The mortality associated with post-transplant lymphoproliferative disorder (PTLD) induced by EBV infection can be reduced by monitoring EBV by polymerase-chain-reaction and rituximab given pre-emptively. We performed a retrospective analysis of the risk factors for the occurrence of EBV infection/disease and EBV-related mortality among 273 consecutive recipients of a T-cell-depleted allo-SCT during two periods: (a) before the implementation of a comprehensive protocol (2006)(2007)(2008) and (b) afterwards (2009)(2010)(2011). EBV infection was detected in 61 (22%) cases, and 28 cases were considered to have had EBV disease. Treatment with antithymocyte globulin was the most important risk factor (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.3-4.2, P ¼ 0.001). After implementation of the protocol, in patients experiencing EBV infection, pre-emptive therapy was started more often and sooner (median 3 vs 6 days, P ¼ 0.002). Moreover, there were fewer cases of monomorphic PTLD (4/33 (12%) vs 11/28 (39%), P ¼ 0.01), and the EBV-related mortality was lower for patients experiencing EBV infection (2/33 (6%) vs 8/28 (29%), OR 0.2; 95% CI 0.05-0.9, P ¼ 0.03). The EBV protocol proved feasible and resulted in faster initiation of pre-emptive therapy, the diagnosis in an earlier stage of EBV disease, and decreased EBV-related mortality.

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

“…21 Pooling results from published studies in HSCT recipients suggest that administration of rituximab results in a positive outcome for approximately 90% patients treated pre-emptively, and 65% with EBV-PTLD. 2,3,11,12,19,20,24,27,[51][52][53][54][55][56][57][58][59][60][61][62] Recent data demonstrate that RI, when applied in combination with rituximab, appears to improve the outcome by over 80%. 3 RI used alone as preemptive therapy resulted in a 68% success rate.…”

“…Neither in vivo/ex vivo CD34-positive selection nor CD3/CD19 depletion prevents EBV-PTLD. 11,31 Allo-HSCT recipients should be closely monitored clinically, together with prospective monitoring for EBV DNA in peripheral blood. Importantly, monitoring and intervention strategies might be individualized, informed by a holistic assessment of EBV-PTLD risk.…”

“…Detection of EBV DNA by PCR of histological extracts is not an appropriate method for PTLD diagnosis given the very high sensitivity but low positive predictive value (PPV) ( Table 2). [10][11][12][13][14][15] The histopathologic criteria of PTLD were defined by Swerdlow and Greig. 16 The WHO classification is most commonly used, with four types of morphological lesions being recognized: polyclonal early lesions, polymorphic, monomorphic (B-cell or T/NK-cell) and classical Hodgkin lymphoma-type PTLD.…”

Identification of IG-clonality status as a pre-treatment predictor for mortality in patients with immunodeficiency-associated Epstein-Barr virus-related lymphoproliferative disorders

“…Histology was examined by 2 experienced hematopathologists and designated either monomorphous or reactive/polymorphous (no Burkitt-or Hodgkin-type lesion was included) according to the WHO criteria. 4 In the majority of the cases, IG clonality was detected in multiple PCRs. There was no clear difference in clonality pattern in monomorphic subtype PTLDs versus the reactive/polymorphic PTLDs, albeit the last group tended to have more cases showing monoclonality with a polyclonal background, although this is not exclusively seen in this group.…”

“…Despite efforts to standardize the pathological classification of EBV-LPD, 4 neither histology nor IG clonality has been shown to consistently predict outcome. [5][6][7] Nevertheless, comprehensive IG clonality testing, with a high detection rate of clonality, allows an objective pathological parameter to be re-evaluated in risk stratification of EBV-LPD.…”