Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal

Abstract

No optimum treatment of iatrogenic immunodeficiency-associated lymphoproliferative disorders due to methotrexate in patients with rheumatoid arthritis (MTX-LPD) has yet been established, although MTX withdrawal is known to have a substantial effect on tumor regression. Here, we retrospectively analyzed 20 cases of MTX-LPD. Tumor shrinkage occurred in 18 of 20 cases, but only following MTX withdrawal. This tumor regression ratio was considerably better than in previous reports, and appeared due to longer "watchful waiting." Lymphocyte recovery at 2 weeks after MTX withdrawal was significantly higher in cases with tumor regression in 1 month than in those without tumor regression (p = 0.001). Median time to maximal efficacy after MTX cessation in cases without chemotherapy was 12 weeks (range 2-76). In conclusion, watchful waiting for a longer period after MTX cessation with observation of early lymphocyte recovery and uninterrupted continuation of other anti-rheumatoid drugs may be an acceptable management plan for MTX-LPD.

Methotrexate-associated Intravascular Large B-cell Lymphoma in a Patient with Rheumatoid Arthritis

“…There is a growing interest in MTX-LPD regression without chemotherapy. The maximum shrinkage was obtained at approximately 8 weeks after the cessation of MTX (14). However, her FDG-PET/CT revealed extended involvement, which forced us administer R-CHOP because early chemotherapy has been reported to lead to a favorable outcome in IVLBCL (7,15).…”

Methotrexate‐Associated Lymphoproliferative Disorder: A Rare Case of Large Liver Tumors

“…The histopathological features of MTX‐LPD are diverse, varying from polyclonal to monoclonal lymphocytosis . The frequency of extranodal involvement, including that of the lung, head, and neck, is relatively high; but hepatic involvement is extremely rare …”

“…Although there is no standard treatment for MTX‐LPD, approximately 60%‐90% of MTX‐LPD patients show spontaneous regression following MTX withdrawal, which is seen more frequently in cases positive for EBER on immunohistochemistry . Therefore, a watch‐and‐wait strategy may be the first choice for MTX‐LPD management, especially in EBER‐positive cases.…”

Methotrexate-associated lymphoproliferative disorder complicated by severe acute respiratory failure and ileal perforation:a case report

“…Saito et al and Inui et al reported that a significant decrease in absolute lymphocyte count at LPD diagnosis and its restoration after MTX withdrawal were associated with spontaneous regression of LPD that developed during MTX treatment 20,21) ; however, Takanashi et al reported opposing results 22) . Further research is therefore needed to determine if a rapid recovery of absolute lymphocyte count after MTX withdrawal represents a predictive factor for LPD regression.…”