Distinct patterns of lymphocyte count transition in lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate

Rheumatology (Oxford). 2017 Jun 1;56(6):940-946. doi: 10.1093/rheumatology/kex002.


Objective: To clarify the characteristics of lymphoproliferative disorder (LPD) in patients with RA treated with MTX.

Methods: Among 33 patients developing LPD during MTX treatment, 20 LPDs regressed spontaneously within 12 weeks after MTX cessation (regressive LPD), and 13 did not regress and most of them died or needed chemotherapy (persistent LPD). The control group consisted of 66 clinically matched MTX-treated RA patients without LPD. The clinical characteristics were compared between these three groups.

Results: While no significant differences were found in clinical RA and LPD features among the three groups, the absolute lymphocyte number of the two LPD groups at LPD diagnosis was significantly lower than the control group (497/µl in the regressive vs 680/µl in the persistent vs 1400/µl in the control, P < 0.05). After MTX withdrawal, the lymphocyte number in the regressive group rapidly recovered to 1214/µl (P < 0.01) by week 2 and was thereafter maintained at an equivalent level to the control group. In contrast, lymphocyte level in the persistent group did not show significant increase throughout 12 weeks (620/µl at week 2, P = 0.57). Changes in lymphocyte number following MTX withdrawal clearly distinguished the regressive LPD from the persistent LPD.

Conclusion: A significant decrease in lymphocyte count at the LPD diagnosis and its restoration after MTX withdrawal were markedly associated with spontaneous regression of LPD developing during MTX treatment.

Keywords: lymphocyte; lymphoproliferative disorder; methotrexate; predictor; prognosis; regression; rheumatoid arthritis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Case-Control Studies
  • Female
  • Humans
  • Lymphocyte Count
  • Lymphopenia / chemically induced
  • Lymphoproliferative Disorders / chemically induced*
  • Male
  • Methotrexate / adverse effects*
  • Middle Aged
  • Retrospective Studies


  • Antirheumatic Agents
  • Methotrexate