Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders with a T- or NK-cell phenotype

J Clin Exp Hematop. 2019;59(2):56-63. doi: 10.3960/jslrt.19013.


Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) with a T- or NK-cell phenotype are markedly rare, with only a limited number of cases having been reported thus far. Methotrexate (MTX) is the most common agent used for OIIA-LPD patients, and 43 cases of MTX-associated T-LPDs (MTX T-LPDs) and five cases of MTX-associated NK/T-LPDs (MTX NK-LPDs) have been described. In addition to MTX T-LPDs and MTX NK/T-LPDs, T-LPD and NK/T-LPDs have been reported in patients receiving other immunosuppressive agents such as thiopurines, TNF antagonists, and cyclosporine. Hepatosplenic T-cell lymphoma (HSTL) is specifically associated with iatrogenic immunodeficiency, and 10% of HSTL cases develop in patients receiving thiopurines and/or TNF antagonists for inflammatory bowel disease (IBD). In this review, we focused on MTX T-LPD, MTX NK/T-LPD, and HSTL in patients with IBD. These T- and NK/T-cell associated OIIA-LPDs are the most common in daily medical practice.

Keywords: T or NK/T-cell lymphoma; hepatosplenic T-cell lymphoma; inflammatory bowel disease; methotrexate; other iatrogenic immunodeficiency-associated lymphoproliferative disorder.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Iatrogenic Disease / epidemiology
  • Immunologic Deficiency Syndromes / chemically induced
  • Immunologic Deficiency Syndromes / pathology*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Inflammatory Bowel Diseases / drug therapy
  • Lymphoproliferative Disorders / chemically induced
  • Lymphoproliferative Disorders / pathology*
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology*


  • Immunosuppressive Agents
  • Methotrexate