Medical Oncology

, Volume 26, Issue 1, pp 1–9

Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature

  • Rita Rizzi
  • Paola Curci
  • Mario Delia
  • Erminia Rinaldi
  • Antonia Chiefa
  • Giorgina Specchia
  • Vincenzo Liso
Original Paper


There are a number of intriguing reports of lymphoproliferative disorders (LPDs) diagnosed during immunosuppressive treatment for underlying autoimmune disease, and spontaneously abated shortly after treatment discontinuation. Such LPDs, completely or partially regressing, occur in the clinical setting of “Methotrexate (MTX)-associated LPDs”, recognized by the World Health Organization (WHO) among the “Immunodeficiency-associated LPDs”. We identified 26 literature patients achieving spontaneous complete remission (CR) of their LPD, and eight others showing partial remission (PR). Most of them were affected by rheumatoid arthritis, received low-dose and long-term pulsed MTX alone or combined with other immunosuppressants, and developed a lymphoma. By reviewing the patients achieving CR, the following can be drawn: the absence of a unique type of LPD, the occurrence of an increased incidence of diffuse large B cell lymphoma as well as of frequent extranodal involvement, and EBV-infection. Further, CR mostly occurred within 4 weeks after discontinuation of immunosuppressant, and appeared to be persistent overtime. Conversely in the patients experiencing PR, the interval between discontinuation of immunosuppressive treatment and clinical response was mostly reported as longer than 4 weeks; moreover, in many cases the persistence of LPD or its progression induced to start cytotoxic therapy. Increased awareness is needed on the possible occurrence of LPD spontaneous remission following immunosuppressant discontinuation, after that it is therefore advisable to have a careful monitoring of the patient for some weeks, before starting cytotoxic therapy.


Autoimmune disease Immunosuppressant Methotrexate Lymphoma Spontaneous remission 


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Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Rita Rizzi
    • 1
  • Paola Curci
    • 1
  • Mario Delia
    • 1
  • Erminia Rinaldi
    • 1
  • Antonia Chiefa
    • 1
  • Giorgina Specchia
    • 1
  • Vincenzo Liso
    • 1
  1. 1.Hematology Section, Department of Pathology and HematologyBari University Medical SchoolBariItaly

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