Post-transplantation lymphoproliferative disorder after haematopoietic stem cell transplantation

Ann Hematol. 2021 Apr;100(4):865-878. doi: 10.1007/s00277-021-04433-y. Epub 2021 Feb 6.

Abstract

Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication of haematopoietic stem cell transplantation (HSCT), occurring in a setting of immune suppression and dysregulation. The disease is in most cases driven by the reactivation of the Epstein-Barr virus (EBV), which induces B cell proliferation through different pathomechanisms. Beyond EBV, many factors, variably dependent on HSCT-related immunosuppression, contribute to the disease development. PTLDs share several features with primary lymphomas, though clinical manifestations may be different, frequently depending on extranodal involvement. According to the WHO classification, histologic examination is required for diagnosis, allowing also to distinguish among PTLD subtypes. However, in cases of severe and abrupt presentation, a diagnosis based on a combination of imaging studies and EBV-load determination is accepted. Therapies include prophylactic and pre-emptive interventions, aimed at eradicating EBV proliferation before symptoms onset, and targeted treatments. Among them, rituximab has emerged as first-line option, possibly combined with a reduction of immunosuppression, while EBV-specific cytotoxic T lymphocytes are effective and safe alternatives. Though prognosis remains poor, survival has markedly improved following the adoption of the aforementioned treatments. The validation of innovative, combined approaches is the future challenge.

Keywords: EBV; HSCT; PTLD; Transplantation.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Child
  • Diagnosis, Differential
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 4, Human / pathogenicity
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Lymphoproliferative Disorders / epidemiology
  • Lymphoproliferative Disorders / etiology*
  • Lymphoproliferative Disorders / therapy
  • Lymphoproliferative Disorders / virology
  • MicroRNAs / genetics
  • Middle Aged
  • Mutation
  • Prognosis
  • Risk Factors
  • Rituximab / therapeutic use
  • T-Lymphocytes, Cytotoxic / transplantation
  • Transplantation Conditioning / adverse effects
  • Transplantation, Homologous / adverse effects
  • Virus Activation

Substances

  • Immunosuppressive Agents
  • MicroRNAs
  • Rituximab