Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: Comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types

Cancer Sci. 2017 Jun;108(6):1271-1280. doi: 10.1111/cas.13249. Epub 2017 May 23.

Abstract

Patients with rheumatoid arthritis often develop methotrexate-associated lymphoproliferative disorders (MTX-LPD) during MTX treatment. MTX-LPD occasionally regresses spontaneously after simply discontinuing MTX treatment. In patients without spontaneous regression, additional chemotherapy is required to avoid disease progression. However, the differences between spontaneous and non-spontaneous regression have yet to be elucidated. To clarify the factors important for spontaneous regression, we analyzed the clinicopathological features of 51 patients with rheumatoid arthritis who developed MTX-LPD (diffuse large B-cell lymphoma [DLBCL]-type [n = 34] and classical Hodgkin lymphoma [CHL]-type [n = 17]). We examined the interval from MTX discontinuation to the administration of additional chemotherapy. The majority of DLBCL-type MTX-LPD patients (81%) exhibited remission with MTX discontinuation alone. In contrast, the majority of CHL-type MTX-LPD patients (76%) required additional chemotherapy. This difference was statistically significant (P = 0.001). However, overall survival was not significantly different between DLBCL-type and CHL-type (91% vs 94%, respectively; P > 0.05). Thus, the morphological differences in the pathological findings of MTX-LPD may be a factor for spontaneous or non-spontaneous regression after discontinuation of MTX.

Keywords: Epstein-Barr virus; histological findings; methotrexate-associated lymphoproliferative disorders; rheumatoid arthritis; spontaneous remission.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / drug therapy
  • Disease Progression
  • Female
  • Hodgkin Disease / chemically induced*
  • Hodgkin Disease / pathology*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / chemically induced*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Lymphoproliferative Disorders / chemically induced*
  • Lymphoproliferative Disorders / pathology*
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged

Substances

  • Methotrexate