Preemptive Management of Epstein-Barr Virus Reactivation After Hematopoietic Stem-Cell Transplantation

Ahmad, Imran; Cau, Nguyen V.; Kwan, John; Maaroufi, Younes; Meuleman, Nathalie; Aoun, Mickaël; Lewalle, Philippe; Martiat, Philippe; Crokaert, Françoise; Bron, Dominique

doi:10.1097/tp.0b013e31819f1c49

Cited by 56 publications

(42 citation statements)

References 18 publications

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“…We were struck by the vast variation in peripheral blood EBV load at the time of PTLD presentation; ranging over a sevenfold log 10 scale. However, viral load at symptomatic presentation of SCT-PTLD was frequently below conventionally adopted thresholds; 16,[18][19][20][21]27 p40 000 copies/mL and p10 000 copies/mL in 45% and 23% of cases, respectively. It follows that reliance on a viral load threshold per se to predict SCT-PTLD jeopardises timely diagnoses.…”

Section: Survivalmentioning

confidence: 99%

“…[16][17][18] Furthermore, 'pre-emptive' treatment strategies in response to EBV DNAemia, with or without accompanying clinical evidence of EBV-associated disease, have been widely incorporated into clinical practice. 14,16,[18][19][20][21] However, this has been predominantly based on uncontrolled, single-centre studies encompassing heterogeneous methods of T-cell depletion and small numbers of PTLD events.…”

Section: Introductionmentioning

confidence: 99%

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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

Fox

Burns

Parker

et al. 2013

Bone Marrow Transplant

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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. Sixtynine 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 p10 000 and p40 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 ¼ 0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P ¼ 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.

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Section: Survivalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Fox

Burns

Parker

et al. 2013

Bone Marrow Transplant

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“…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.…”

Section: Management Strategiesmentioning

confidence: 99%

“…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.…”

Section: Definitions and Diagnostic Criteriamentioning

confidence: 99%

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

Styczyński¹,

Velden²,

Fox³

et al. 2016

Haematologica

306

375

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E pstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virusspecific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. Management of Epstein-Barr Virus infections

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“…An EBV load above the laboratory's established threshold for PTLD should be conveyed to the clinician immediately so it may trigger a search for putative sites of disease followed by biopsy, when reasonable, to establish a histopathologic diagnosis. Even in the absence of biopsyproven PTLD, preemptive intervention may be used to resolve laboratory-detected disease (3,60,110,185). Preemptive therapy may include reducing immunosuppression and infusing anti-CD20 antibody or donor T cells.…”

Section: Clinical Indications For Testingmentioning

confidence: 99%

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

2010

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SUMMARYEpstein-Barr virus (EBV) DNA measurement is being incorporated into routine medical practice to help diagnose, monitor, and predict posttransplant lymphoproliferative disorder (PTLD) in immunocompromised graft recipients. PTLD is an aggressive neoplasm that almost always harbors EBV DNA within the neoplastic lymphocytes, and it is often fatal if not recognized and treated promptly. Validated protocols, commercial reagents, and automated instruments facilitate implementation of EBV load assays by real-time PCR. When applied to either whole blood or plasma, EBV DNA levels reflect clinical status with respect to EBV-related neoplasia. While many healthy transplant recipients have low viral loads, high EBV loads are strongly associated with current or impending PTLD. Complementary laboratory assays as well as histopathologic examination of lesional tissue help in interpreting modest elevations in viral load. Circulating EBV levels in serial samples reflect changes in tumor burden and represent an effective, noninvasive tool for monitoring the efficacy of therapy. In high-risk patients, serial testing permits early clinical intervention to prevent progression toward frank PTLD. Restoring T cell immunity against EBV is a major strategy for overcoming PTLD, and novel EBV-directed therapies are being explored to thwart virus-driven neoplasia.

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Preemptive Management of Epstein-Barr Virus Reactivation After Hematopoietic Stem-Cell Transplantation

Cited by 56 publications

References 18 publications

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

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

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

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

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