Posttransplant Lymphoproliferative Disease Guidelines

Updated: Aug 09, 2018
  • Author: Phillip M Garfin, MD, PhD; Chief Editor: Ron Shapiro, MD  more...
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Guidelines

Guidelines Summary

Guidelines for the management of PTLD have been published by the National Comprehensive Cancer Network (NCCN) and the American Society of Transplantation (AST). 

Diagnosis

The NCCN guideline for PTLD, which is integrated into the larger B-cell lymphoma guideline, provides the following algorithm to diagnose the disorder with steps categorized as either "essential" or "useful under certain circumstances." [76]

Essential steps include the following:

  • Adequate immunophenotyping by immunohistochemistry (IHC) panel, with or withoutor cell surface marker analysis by flow cytometry
  • Epstein-Barr virus (EBV) evaluation by EBV latent membrane protein 1 (LMP1) or Epstein–Barr encoding region in situ hybridization (EBER-ISH); EBER-ISH recommended if EBV-LMP1 is negative

Tests useful under certain circumstances include the following:

  • Additional immunophenotyping
  • Molecular analysis to detect IgH gene rearrangements
  • BCL6 gene mutation analysis— BCL6 positivity is associated with poor response to immunosuppression reduction
  • EBV evaluation by Southern blot

AST guidelines recommend the following for the diagnosis of PTLD [77]

  • Cytomegalovirus (CMV) status testing
  • Viral-load testing for EBV
  • Total body CT scan (head to pelvis) 
  • Immunophenotyping to determine lineage and therapy dependent markers (ie, CD20) 
  • Molecular genetic markers of antigen-receptor genes to assess clonality
  • Donor versus recipient origin

Treatment

According to the NCCN guidelines, treatment depends on the PTLD subtype and has varying rates of response. Reduction in immunosuppression (RI) is the initial treatment in nearly all cases according to the guideline. However, response is variable and patients should be closely monitored. Additional treatment options vary according to the World Health Organization (WHO) classification. [76]

Early lesions

  • For patients with a complete response (CR), re-escalation of immunosuppression should be individualized, with monitoring of EBV viral load by PCR assays and of graft organ function
  • For patients with persistent or progression, second-line treatment with rituximab

AST guidelines concur with the recommendations above, but also suggest complete or partial surgical resection, as well as local radiotherapy as adjunctive therapy along with reduced immunosuppression. [77]

Monomorphic PTLD (B-cell type)

 RI if possible, with or without one of the following:

  • Rituximab
  • Rituximab as part of a concurrent or sequential chemoimmunotherapy regimen

Polymorphic PTLD

For patients with localized disease, RI if possible plus one of the following:

  • Rituximab
  • Radiation therapy (RT) with or without rituximab
  • Surgery with or without rituximab

For patients with systemic disease, RI if possible plus one of the following:

  • Rituximab
  • Rituximab as part of a concurrent or sequential chemoimmunotherapy regimen