Skip to main content
Erschienen in: Annals of Hematology 9/2018

30.04.2018 | Original Article

The prognostic value of positron emission tomography/computed tomography in rheumatoid arthritis patients with methotrexate-associated lymphoproliferative disorders

verfasst von: Satoshi Takanashi, Tomonori Nakazato, Yoshinobu Aisa, Chisako Ito, Hideki Arakaki, Yuki Osada, Motoharu Hirano, Takehiko Mori

Erschienen in: Annals of Hematology | Ausgabe 9/2018

Einloggen, um Zugang zu erhalten

Abstract

Recently, methotrexate-associated lymphoproliferative disorders (MTX-LPDs) in rheumatoid arthritis (RA) have been found to commonly occur in association with iatrogenic immunodeficiency. Several factors have been reported to be related to the prognosis. We herein investigate the efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the prognosis of MTX-LPD. We performed a retrospective analysis of the clinical features, characteristics, and outcomes of 18 patients with MTX-LPDs who were treated from 2004 to 2015. All of the patients were diagnosed with MTX-LPD based on the histological examination of biopsy specimens. Spontaneous regression was detected after the cessation of MTX in 5 of 18 cases (28%). The maximum standardized uptake value (SUVmax) of the FDG uptake on PET/CT was significantly lower, and the maximum size of the LPD-associated tumor was significantly smaller among the patients who showed spontaneous regression (p = 0.01, p = 0.04, respectively). Both the SUVmax and the maximum tumor size were related to better overall survival (p = 0.02, p = 0.04, respectively). Thus, PET/CT can be used to predict spontaneous regression and the prognosis at the diagnosis of MTX/LPD. Cases that showed spontaneous regression never relapsed during the follow-up period, despite the usage of several anti-rheumatoid arthritis drugs, including biological agents. The early detection of LPDs and the early cessation of MTX are important for the management of RA patients. An evaluation by F-FDG-PET/CT can be useful for predicting spontaneous regression and the prognosis.
Literatur
1.
Zurück zum Zitat Gaulard P, Swerdlow SH, Harris NL, Jaffe ES, Sundström C (2008) Other iatrogenic immunodeficiency-associated lymphoproliferative disorders. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) World Health Organization classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 350–351 Gaulard P, Swerdlow SH, Harris NL, Jaffe ES, Sundström C (2008) Other iatrogenic immunodeficiency-associated lymphoproliferative disorders. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) World Health Organization classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 350–351
2.
Zurück zum Zitat Salliot C, van der Heijde D (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68:1100–1104CrossRefPubMed Salliot C, van der Heijde D (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68:1100–1104CrossRefPubMed
3.
Zurück zum Zitat Ellman MH, Hurwitz H, Thomas C, Kozloff M (1991) Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate. J Rheumatol 18:1741–1743PubMed Ellman MH, Hurwitz H, Thomas C, Kozloff M (1991) Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate. J Rheumatol 18:1741–1743PubMed
4.
Zurück zum Zitat Salloum E, Cooper DL, Howe G, Lacy J, Tallini G, Crouch J (1996) Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases. J Clin Oncol 14:1943–1949CrossRefPubMed Salloum E, Cooper DL, Howe G, Lacy J, Tallini G, Crouch J (1996) Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases. J Clin Oncol 14:1943–1949CrossRefPubMed
5.
Zurück zum Zitat Mariette X, Cazals-Hatem D, Warszawki J, Liote F, Balandraud N, Sibilia J (2002) Investigators of the Club Rhumatismes et Inflammation. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 99:3909–3915CrossRefPubMed Mariette X, Cazals-Hatem D, Warszawki J, Liote F, Balandraud N, Sibilia J (2002) Investigators of the Club Rhumatismes et Inflammation. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 99:3909–3915CrossRefPubMed
6.
Zurück zum Zitat Kamel OW, van de Rijn M, LeBrun DP, Weiss LM, Warnke RA, Dorfman RF (1994) Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: frequency of Epstein-Barr virus and other features associated with immunosuppression. Hum Pathol 25:638–643CrossRefPubMed Kamel OW, van de Rijn M, LeBrun DP, Weiss LM, Warnke RA, Dorfman RF (1994) Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: frequency of Epstein-Barr virus and other features associated with immunosuppression. Hum Pathol 25:638–643CrossRefPubMed
7.
Zurück zum Zitat Tokuhira M, Watanabe R, Nemoto T, Sagawa M, Tomikawa T, Tamaru J (2012) Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis. Leuk Lymphoma 53:616–623CrossRefPubMed Tokuhira M, Watanabe R, Nemoto T, Sagawa M, Tomikawa T, Tamaru J (2012) Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis. Leuk Lymphoma 53:616–623CrossRefPubMed
8.
Zurück zum Zitat Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y (2007) Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 34:322–340PubMed Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y (2007) Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 34:322–340PubMed
9.
Zurück zum Zitat Rizzi R, Curci P, Delia M, Rinaldi E, Chiefa A, Specchia G, Liso V (2009) Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature. Med Oncol 26:1–9CrossRefPubMed Rizzi R, Curci P, Delia M, Rinaldi E, Chiefa A, Specchia G, Liso V (2009) Spontaneous remission of “methotrexate-associated lymphoproliferative disorders” after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature. Med Oncol 26:1–9CrossRefPubMed
10.
Zurück zum Zitat Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMed
11.
Zurück zum Zitat Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586CrossRefPubMed Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586CrossRefPubMed
12.
Zurück zum Zitat Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17:1244CrossRefPubMed Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17:1244CrossRefPubMed
13.
Zurück zum Zitat Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458CrossRefPubMed Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458CrossRefPubMed
14.
Zurück zum Zitat Thomas E, Brewster DH, Black RJ, Macfarlane GJ (2000) Risk of malignancy among patients with rheumatic conditions. Int J Cancer 88:497–502CrossRefPubMed Thomas E, Brewster DH, Black RJ, Macfarlane GJ (2000) Risk of malignancy among patients with rheumatic conditions. Int J Cancer 88:497–502CrossRefPubMed
15.
Zurück zum Zitat Smitten AL, Simon TA, Hochberg MC, Suissa S (2008) Meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther 10:R45CrossRefPubMedPubMedCentral Smitten AL, Simon TA, Hochberg MC, Suissa S (2008) Meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther 10:R45CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Hsiao SC, Ichinohasama R, Lin SH, Liao YL, Chang ST, Cho CY (2009) EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate. Pathol Res Pract 205:43–49CrossRefPubMed Hsiao SC, Ichinohasama R, Lin SH, Liao YL, Chang ST, Cho CY (2009) EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate. Pathol Res Pract 205:43–49CrossRefPubMed
18.
Zurück zum Zitat Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F (2006) Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54:692–701CrossRefPubMed Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F (2006) Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54:692–701CrossRefPubMed
19.
Zurück zum Zitat Inui Y, Matsuoka H, Yakushijin K, Okamura A, Shimada T, Yano S (2015) Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal. Leuk Lymphoma 56:3045–3051CrossRefPubMed Inui Y, Matsuoka H, Yakushijin K, Okamura A, Shimada T, Yano S (2015) Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal. Leuk Lymphoma 56:3045–3051CrossRefPubMed
20.
Zurück zum Zitat Niitsu N, Okamoto M, Nakamine H, Hirano M (2010) Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate. Cancer Sci 101:1309–1313CrossRefPubMed Niitsu N, Okamoto M, Nakamine H, Hirano M (2010) Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate. Cancer Sci 101:1309–1313CrossRefPubMed
21.
Zurück zum Zitat Kamel OW, van de Rijn M, Weiss LM, Del Zoppo GJ, Hench PK, Robbins BA (1993) Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 328:1317–1321CrossRefPubMed Kamel OW, van de Rijn M, Weiss LM, Del Zoppo GJ, Hench PK, Robbins BA (1993) Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 328:1317–1321CrossRefPubMed
22.
Zurück zum Zitat Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D (2013) Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: history, Epstein-Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol 91:20–28CrossRefPubMed Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D (2013) Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: history, Epstein-Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol 91:20–28CrossRefPubMed
23.
Zurück zum Zitat Watanabe S, Manabe O, Hirata K, Oyama-Manabe N, Hattori N, Kikuchi Y (2016) The usefulness of (18)F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD). BMC Cancer 16:635CrossRefPubMedPubMedCentral Watanabe S, Manabe O, Hirata K, Oyama-Manabe N, Hattori N, Kikuchi Y (2016) The usefulness of (18)F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD). BMC Cancer 16:635CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Feng WH, Cohen JI, Fischer S, Li L, Sneller M, Goldbach-Mansky R (2004) Reactivation of latent Epstein-Barr virus by methotrexate; a potential contributor to methotrexate-associated lymphomas. J Natl Cancer Inst 96:1691–1702CrossRefPubMed Feng WH, Cohen JI, Fischer S, Li L, Sneller M, Goldbach-Mansky R (2004) Reactivation of latent Epstein-Barr virus by methotrexate; a potential contributor to methotrexate-associated lymphomas. J Natl Cancer Inst 96:1691–1702CrossRefPubMed
25.
Zurück zum Zitat Alspaugh MA, Henle G, Lennette ET, Henle W (1981) Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. J Clin Invest 67:1134–1140CrossRefPubMedPubMedCentral Alspaugh MA, Henle G, Lennette ET, Henle W (1981) Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis. J Clin Invest 67:1134–1140CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Balandraud N, Meynard JB, Auger I, Sovran H, Mugnier B, Reviron D (2003) Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: accurate quantification using real-time polymerase chain reaction. Arthritis Rheum 48:1223–1228CrossRefPubMed Balandraud N, Meynard JB, Auger I, Sovran H, Mugnier B, Reviron D (2003) Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: accurate quantification using real-time polymerase chain reaction. Arthritis Rheum 48:1223–1228CrossRefPubMed
27.
Zurück zum Zitat Sawada S, Takei M (2003) Epstein-Barr virus etiology in rheumatoid synovitis. Autoimmun Rev 4:106–110CrossRef Sawada S, Takei M (2003) Epstein-Barr virus etiology in rheumatoid synovitis. Autoimmun Rev 4:106–110CrossRef
28.
Zurück zum Zitat Adams AE, Zwicker J, Curiel C, Kadin ME, Falchuk KR, Drews R (2004) Aggressive cutaneous T-cell lymphomas after TNFalpha blockade. J Am Acad Dermatol 51:660–662CrossRefPubMed Adams AE, Zwicker J, Curiel C, Kadin ME, Falchuk KR, Drews R (2004) Aggressive cutaneous T-cell lymphomas after TNFalpha blockade. J Am Acad Dermatol 51:660–662CrossRefPubMed
29.
Zurück zum Zitat Diak P, Siegel J, La Grenade L, Choi L, Lemery S, McMahon A (2010) Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum 62:2517–2524CrossRefPubMed Diak P, Siegel J, La Grenade L, Choi L, Lemery S, McMahon A (2010) Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum 62:2517–2524CrossRefPubMed
Metadaten
Titel
The prognostic value of positron emission tomography/computed tomography in rheumatoid arthritis patients with methotrexate-associated lymphoproliferative disorders
verfasst von
Satoshi Takanashi
Tomonori Nakazato
Yoshinobu Aisa
Chisako Ito
Hideki Arakaki
Yuki Osada
Motoharu Hirano
Takehiko Mori
Publikationsdatum
30.04.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 9/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3327-4

Weitere Artikel der Ausgabe 9/2018

Annals of Hematology 9/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.