Spontaneous Regression of Methotrexate-related Lymphoproliferative Disorder with T-cell Large Granular Lymphocytosis

Abstract

Spontaneous regression of methotrexate-related lymphoproliferative disorders (MTX-LPDs) occurs in some patients after withdrawal of MTX. However, the mechanisms by which MTX withdrawal contributes to the spontaneous regression of MTX-LPDs have not been fully elucidated. We herein show that spontaneous regression of MTX-LPDs is associated with the development of significant and transient T-cell large granular lymphocyte (T-LGL) lymphocytosis induced by MTX withdrawal. Since T-LGLs show strong cytotoxicity, their expansion may contribute to the spontaneous regression of lymphoma. Therefore, the development of T-LGL lymphocytosis maybe associated with a favorable prognosis in MTX-LPD patients.

Lymphoproliferative disorder in an elderly rheumatoid arthritis patient after longterm oral methotrexate administration: A case report

“…Spontaneous resolution of LPD after withdrawal of MTX treatment is observed in ~50% of all affected patients (12,14,15). However, cases of patients with LPD progression after the discontinuation of MTX have also been reported (12,15).…”

“…The progression or resolution of LPD is not only affected by MTX treatment per se, but also by the immune status of the host, which, as previously described, is affected by RA pathogenesis. However, the majority of reports recommend interrupting MTX treatment upon development of MTX-LPD (12,(14)(15)(16). In a previous study, 23 patients (76.7%) achieved regression of LPD by MTX withdrawal (16).…”

Transient Stress Lymphocytosis in a Child: A Case Report and Systematic Review of the Literature

“…For completeness, we provide the following summary of the articles that were excluded, as they did not occur in traumatic/emergent settings. TSL was described in splenic contraction secondary to dasatinib [ 14 ], acute illness during chronic lymphocytic leukemia [ 15 ], exposure to catecholamines [ 16 , 17 ] and glucocorticoids [ 18 ], early-phase infection of human immunodeficiency virus [ 19 ], infection with human T-lymphotropic virus type 1 [ 20 ], reactivation of Epstein Barr virus or hepatitis B virus after allogeneic hematopoietic stem cell transplantation [ 21 , 22 ], as an effect of anti-cancer medications such as methotrexate [ 23 ] and tirabrutinib [ 24 ], and in the recovery phase of the recently described multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection [ 25 ]. One case described transient lymphocytosis, but no cause was assigned (idiopathic) [ 26 ].…”

Treatment of advanced stage methotrexate-associated lymphoproliferative disorders (MTX-LPDs) with methotrexate discontinuation

“…Immunosuppressive agents (especially MTX) have a well-known association with LPDs 1–3. Improvement or regression of MTX-LPD lesions occurs in 30%–59% of patients following discontinuation of MTX 1 2 4.…”