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Abstract Number: 419

A Long Term Observation Of Rheumatoid Arthritis Who Developed Methotrexate Related Lymphoproliferative Disorders

Yukiko Kamogawa1, Kyohei Nakamura2, Ryu Watanabe2, Tsuyoshi Shirai1, Yoko Fujita3, Yuko Shirota4, Noriko Fukuhara1, Hiroshi Fujii2, Shinichiro Saito5, Tomonori Ishii2 and Hideo Harigae2, 1Tohoku University, Sendai, Japan, 2Department of Hematology and Rheumatology, Tohoku University, Sendai, Japan, 3Department of Hematolgy and rheumatolgy, Tohoku University, Sendai, Japan, 4Department of Hematology and Rheumatolgy, Tohoku University, Sendai, Japan, 5Department of hematology and rheumatology, Tohoku University, Sendai, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Malignancy, methotrexate (MTX), remission, rheumatoid arthritis (RA) and rituximab

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Session Information

Session Title: Rheumatoid Arthritis - Clinical Aspects I: Comorbidities in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Methotrexate (MTX) has been increasingly administered by patients with rheumatoid arthritis (RA). In rare cases, we experience development of malignant lymphoma in patients treated with MTX, resulting as methotrexate-associated lymphoproliferative disorders (MTX-LPDs). However, there are few reports about analyzing relation between lymphoma chemotherapy and RA prognosis. We tried to show how anti-tumor therapies affect the activity of RA.

Methods: We retrospectively enrolled 14 RA patients (4 males and 10 females) who had taken MTX and developed lymphoproliferative disorders in Tohoku University Hospital between 2008 and 2013. Then we analyzed the RA disease duration, period of MTX administration, histology of lymphoma including EBER-1 in situ hybridization for Epstein-Barr virus (EBV), chemotherapies, prognosis of RA and how RA was treated thereafter.

Results: The median age of patients at the time of lymphoma diagnosis was 69 years (57-83). The average period of MTX administration was 6.4 years. 7 of 13 patients were diagnosed as diffuse large B-cell lymphoma (DLBCL), 3 as MALT lymphoma (MALT), 1 as peripheral T-cell lymphoma (PTCL), 2 as Hodgkin lymphoma (HL), 1 as Follicular lymphoma (FL). EBER-1 in situ hybridization for EBV showed positive signals in tumor cells in 4 of 11 cases. After withdrawal of MTX, 2 cases of DLBCL, 1 case of PTCL, and 1 case of MALT showed spontaneous regression of tumors. The 10 patients with LPD persisted after MTX withdrawal treated with R-CHOP (n=4), R-VP+R-COP (n=1), Rituximab (n=3) or ABVD (n=2). 7 out of 14 patients presented RA relapse and treated with prednisolone (PSL), Tacrolimus, Iguratimod, Etanercept, or Tocilizumab. 6 out of 8 patients treated with Rituximab kept remission and other 2 relapsed patients showed weak RA activity, required only small amount of PSL but no DMARDs or Biologics.

Conclusion: Administration of Rituximab toward MTX-LPDs thought to have assisted to keep the RA activity low unexpectedly by suppressing auto-reactive B cells.

Patients Background

Pat.

Age

Sex

MTX admi. peri. (year)

Histology

EBER

Chemotherapy

RA relapse

RA treatment

1

64

M

5.5

DLBCL

+

R-CHOP

–

–

2

69

F

5

DLBCL

–

R-CHOP

–

–

3

70

F

N/A

MALT

N/A

Rituximab

–

–

4

74

F

N/A

DLBCL

–

Rituximab

+

PSL

5

57

M

11

DLBCL

–

none

+

Tocilizumab

6

74

F

N/A

DLBCL

–

R-CHOP

+

PSL

7

83

F

1

HL

+

ABVD

+

Tacrolimus

8

57

F

9

PTCL

+

none

+

PSL

9

77

F

N/A

MALT

N/A

Rituximab

–

–

10

65

M

4

DLBCL

–

R-VP�AR-COP

–

–

11

73

M

N/A

FL

–

R-CHOP

–

–

12

67

F

10

HL

+

ABVD

+

Etanercept

13

80

F

10

DLBCL

N/A

none

–

–

14

57

F

2.5

MALT

–

none

+

Iguratimod

 


Disclosure:

Y. Kamogawa,
None;

K. Nakamura,
None;

R. Watanabe,
None;

T. Shirai,
None;

Y. Fujita,
None;

Y. Shirota,
None;

N. Fukuhara,
None;

H. Fujii,
None;

S. Saito,
None;

T. Ishii,
None;

H. Harigae,
None.

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