Methotrexate-associated lymphoproliferative disorders

Methotrexate is used in the treatment of the autoimmune conditions rheumatoid arthritis, dermatomyositis and psoriasis. Lymphoproliferative disorders (LPD) have been reported during the use of methotrexate in all three conditions, but most commonly with rheumatoid arthritis. However, patient with rheumatoid arthritis have a two to twenty fold increased risk of lymphoma and it is not clear whether methotrexate further increases this risk. Lymphoproliferative disease develops approximately 15 years after the onset of the autoimmune disease, a mean duration of methotrexate therapy of 3 years and a median cumulative dose of methotrexate of 0.8 g. Based on the ~100 cases published:

 

proportion of cases of LPD

proportion that are extranodal

EBV positive

Regressed with withdrawal of methotrexate

immunophenotype

  

DLBCL

23/63

7/15

9/17

4/10

usual

Hodgkin lymphoma

15/63

1/12

10/14

2/9

CD15+

Hodgkin-lymphoma-like LPD

4/63

2/4

4/4

4/4

CD15-/CD20+/CD30+

Lymphoplasmacytic lymphoma & atypical lymphoplasmacytic infiltrate

9/63

6/6

3/6

1/3

usual

follicular lymphoma

6/63

2/5

2/5

1/4

 usual

Burkitt lymphoma

3/63

0/1

1/3

0/3

 usual

Peripheral T-cell lymphoma

3/63

-

-

2/2

 usual

Total

63

18/45

30/51

13/34

 

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

This page last revised 24.12.2002.

©SMUHT/PW Bishop