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1. Nabors LB, Palmer CA, Julian BA, Przekwas AM, Kew CE: Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate. Am J Transplant; 2009 May;9(5):1243-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate.
  • Posttransplant lymphoproliferative disorder (PTLD) is an uncommon neoplastic complication of kidney transplantation, affecting about 1% of recipients.
  • It is generally associated with Epstein-Barr virus (EBV) infection of B-lineage lymphocytes.
  • There is little clinical experience with treatment of CNS PTLD due to the relative rarity of the disease other than reduction or withdrawal of immunosuppression, but it is usually fatal.
  • Tissue analysis from the biopsy specimens was positive for EBV material in five of the six patients.
  • All six patients were treated with high-dose intravenous methotrexate (HD IV MTX).
  • Methotrexate was initiated at 8 g/m2, with later adjustments for creatinine clearance.
  • With MTX therapy, four patients have had a sustained complete response, and two had progressive disease and were referred for radiation therapy.
  • No unexpected toxicities were encountered in 37 courses of treatment.
  • HD IV MTX chemotherapy should be considered as an alternative for treatment of CNS PTLD.
  • [MeSH-major] Central Nervous System Diseases / virology. Epstein-Barr Virus Infections / drug therapy. Immunosuppressive Agents / therapeutic use. Kidney Transplantation / adverse effects. Methotrexate / therapeutic use. Myeloproliferative Disorders / drug therapy. Postoperative Complications / drug therapy
  • [MeSH-minor] Humans. Injections, Intravenous. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 19422350.001).
  • [ISSN] 1600-6143
  • [Journal-full-title] American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • [ISO-abbreviation] Am. J. Transplant.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; YL5FZ2Y5U1 / Methotrexate
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2. Kikuchi K, Miyazaki Y, Tanaka A, Shigematu H, Kojima M, Sakashita H, Kusama K: Methotrexate-related Epstein-Barr Virus (EBV)-associated lymphoproliferative disorder--so-called "Hodgkin-like lesion"--of the oral cavity in a patient with rheumatoid arthritis. Head Neck Pathol; 2010 Dec;4(4):305-11
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Methotrexate-related Epstein-Barr Virus (EBV)-associated lymphoproliferative disorder--so-called "Hodgkin-like lesion"--of the oral cavity in a patient with rheumatoid arthritis.
  • Patients affected by autoimmune diseases (rheumatoid arthritis, psoriasis, dermatomyositis) who are treated with methotrexate (MTX) sometimes develop lymphoproliferative disorders (LPDs).
  • In approximately 40% of reported cases, the affected sites have been extranodal, and have included the gastrointestinal tract, skin, lung, kidney, and soft tissues.
  • However, MTX-associated LPD (MTX-LPD) is extremely rare in the oral cavity.
  • Here we report a 69-year-old Japanese woman with rheumatoid arthritis (RA) who developed MTX-LPD resembling Hodgkin's disease--so-called "Hodgkin-like lesion"--in the left upper jaw.
  • Histopathologically, large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells were found to have infiltrated into granulation tissue in the ulcerative oral mucosa.
  • To our knowledge, this is the first reported case of MTX-related EBV-associated LPD (MTX-EBVLPD), "Hodgkin-like lesion", of the oral cavity in a patient with RA.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Arthritis, Rheumatoid / drug therapy. Epstein-Barr Virus Infections / complications. Herpesvirus 4, Human / isolation & purification. Lymphoproliferative Disorders / virology. Methotrexate / adverse effects

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  • (PMID = 20676828.001).
  • [ISSN] 1936-0568
  • [Journal-full-title] Head and neck pathology
  • [ISO-abbreviation] Head Neck Pathol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antirheumatic Agents; 0 / RNA, Viral; YL5FZ2Y5U1 / Methotrexate
  • [Other-IDs] NLM/ PMC2996501
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3. Markasz L, Stuber G, Flaberg E, Jernberg AG, Eksborg S, Olah E, Skribek H, Szekely L: Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells. BMC Cancer; 2006;6:265
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  • [Title] Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells.
  • BACKGROUND: Epstein-Barr virus (EBV) is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP).
  • Reducing the immunosuppression in recipients of solid organ transplants (SOT) or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23-50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts.
  • An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or EBV-specific cytotoxic T-cells.
  • Chemotherapy is used for the non-responding cases only as the second or third line of treatment.
  • The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders.
  • METHODS: As lymphoblastoid cell lines (LCLs) are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity.
  • RESULTS: Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs.
  • LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel.
  • CONCLUSION: Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified.
  • [MeSH-major] Antineoplastic Agents / toxicity. Antiviral Agents / pharmacology. B-Lymphocytes / virology. Cell Transformation, Viral. Herpesvirus 4, Human / physiology. Lymphoma / drug therapy. Lymphoproliferative Disorders / drug therapy

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  • (PMID = 17101045.001).
  • [ISSN] 1471-2407
  • [Journal-full-title] BMC cancer
  • [ISO-abbreviation] BMC Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antiviral Agents
  • [Other-IDs] NLM/ PMC1664586
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4. Ikeda J, Morii E, Tomita Y, Xu JX, Kimura H, Kohara M, Hoshida Y, Aozasa K: Methotrexate-associated lymphoproliferative disorder mimicking composite lymphoma. Int J Hematol; 2006 May;83(4):363-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Methotrexate-associated lymphoproliferative disorder mimicking composite lymphoma.
  • [MeSH-major] Arthritis, Rheumatoid / drug therapy. Immunosuppressive Agents / adverse effects. Lymphoma / chemically induced. Methotrexate / adverse effects

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  • (PMID = 16757440.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; YL5FZ2Y5U1 / Methotrexate
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5. Ishida Y, Asahi A, Wada T, Kanai N, Kobayashi Y, Moriai S, Kishibe K, Harabuchi Y: [Three cases of methotrexate-associated lymphoproliferative disorder (MTX-LPD)]. Nihon Jibiinkoka Gakkai Kaiho; 2008 Aug;111(8):594-8
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  • [Title] [Three cases of methotrexate-associated lymphoproliferative disorder (MTX-LPD)].
  • Methotrexate (MTX) has been increasingly administered to patients with rheumatoid arthritis (RA), resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients.
  • We reported three case of rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy who developed MTX-LPD.
  • When MTX therapy was interrupted, the tonsil was shrank and chemotherapy was not necessary.
  • [MeSH-major] Lymphoproliferative Disorders / chemically induced. Methotrexate / adverse effects
  • [MeSH-minor] Aged. Arthritis, Rheumatoid / drug therapy. Female. Humans

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  • (PMID = 18788425.001).
  • [ISSN] 0030-6622
  • [Journal-full-title] Nihon Jibiinkoka Gakkai kaiho
  • [ISO-abbreviation] Nippon Jibiinkoka Gakkai Kaiho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] YL5FZ2Y5U1 / Methotrexate
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6. Clarke LE, Junkins-Hopkins J, Seykora JT, Adler DJ, Elenitsas R: Methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis presenting in the skin. J Am Acad Dermatol; 2007 Apr;56(4):686-90
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  • [Title] Methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis presenting in the skin.
  • A 91-year-old woman who had been taking methotrexate for approximately 5 years for rheumatoid arthritis developed papules and nodules on her face that enlarged during 6 months.
  • Withdrawal of methotrexate resulted in complete resolution of all lesions within 8 weeks.
  • This case illustrates the rare occurrence of methotrexate-associated lymphoproliferative disorder with primary presentation in the skin and documents clinical and histopathologic progression from early changes to fully developed lesions.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Arthritis, Rheumatoid / drug therapy. Facial Dermatoses / chemically induced. Lymphoproliferative Disorders / chemically induced. Methotrexate / adverse effects

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  • (PMID = 17141365.001).
  • [ISSN] 1097-6787
  • [Journal-full-title] Journal of the American Academy of Dermatology
  • [ISO-abbreviation] J. Am. Acad. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antirheumatic Agents; YL5FZ2Y5U1 / Methotrexate
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7. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Oncologist; 2006 Mar;11(3):263-73
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Clonal disorders of large granular lymphocytes (LGLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells (CD3+) or natural killer (NK) cells (CD3-).
  • The majority of patients with T-cell LGL leukemia have a clinically indolent course with a median survival time >10 years.
  • Immunosuppressive therapy with low-dose methotrexate, cyclophosphamide, or cyclosporine A can control symptoms and cytopenias in more than 50% of patients, but this approach is not curative.
  • Aggressive NK-cell LGL leukemia is usually a rapidly progressive disorder associated with Epstein-Barr virus (EBV), with a higher prevalence in Asia and South America.
  • This disease is usually refractory to conventional chemotherapy, with a median survival time of 2 months.
  • Chronic NK-cell leukemia/lymphocytosis is a rare EBV-negative disorder with an indolent clinical course.
  • [MeSH-major] Leukemia, T-Cell / diagnosis. Leukemia, T-Cell / therapy

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  • (PMID = 16549811.001).
  • [ISSN] 1083-7159
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 76
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8. Kawakami K, Ito R, Watanabe Y, Goto T: [Effective treatment for a methotrexate-associated lymphoproliferative disorder with R-CHOP following administration of rituximab]. Rinsho Ketsueki; 2005 Jul;46(7):517-21
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  • [Title] [Effective treatment for a methotrexate-associated lymphoproliferative disorder with R-CHOP following administration of rituximab].
  • A diagnosis of MTX-associated B-lymphoproliferative disorder was made.
  • The masses persisted, however, so we carried out eight courses of R-CHOP therapy, which induced complete response without any episode of serious infection.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Immunosuppressive Agents / adverse effects. Lymphoproliferative Disorders / drug therapy. Lymphoproliferative Disorders / etiology. Methotrexate / adverse effects
  • [MeSH-minor] Aged. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. Arthritis, Rheumatoid / drug therapy. Cyclophosphamide / administration & dosage. Doxorubicin / administration & dosage. Epstein-Barr Virus Infections / etiology. Humans. Male. Opportunistic Infections / etiology. Prednisolone / administration & dosage. Rituximab. Vincristine / administration & dosage

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  • (PMID = 16440745.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Immunosuppressive Agents; 4F4X42SYQ6 / Rituximab; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; 9PHQ9Y1OLM / Prednisolone; YL5FZ2Y5U1 / Methotrexate; VAP-cyclo protocol
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9. Pastor-Nieto MA, Kilmurray LG, López-Chumillas A, O'Valle F, García-Del Moral R, Puig AM, Bautista P: [Methotrexate-associated lymphoproliferative disorder presenting as oral ulcers in a patient with rheumatoid arthritis]. Actas Dermosifiliogr; 2009 Mar;100(2):142-6
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  • [Title] [Methotrexate-associated lymphoproliferative disorder presenting as oral ulcers in a patient with rheumatoid arthritis].
  • Methotrexate-associated lymphoproliferative disorders are a heterogeneous group of lymphoid proliferations or lymphomas that develop in patients with autoimmune diseases treated using methotrexate.
  • These lymphoproliferative disorders are often associated with Epstein-Barr virus infection and occasionally regress after the withdrawal of methotrexate therapy.
  • The lymphoproliferative disorder in this case was diffuse large B-cell lymphoma, unusually presenting as oral ulcers in a 79-year-old woman on treatment with methotrexate for longstanding rheumatoid arthritis.
  • Withdrawal of methotrexate therapy led to complete remission within 6 weeks, and the patient is alive and disease-free 18 months after the diagnosis was made.
  • The oral cavity is not often involved in the initial presentation of methotrexate-associated lymphoproliferative disorders, and presentation with intraoral ulcers is very rare.
  • We have performed a review of the literature on methotrexate-associated lymphoproliferative disorders presenting as ulcers in the oral cavity.
  • [MeSH-major] Arthritis, Rheumatoid / drug therapy. Immunosuppressive Agents / adverse effects. Lymphoma, Large B-Cell, Diffuse / etiology. Methotrexate / adverse effects. Oral Ulcer / etiology

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  • (PMID = 19445880.001).
  • [ISSN] 0001-7310
  • [Journal-full-title] Actas dermo-sifiliográficas
  • [ISO-abbreviation] Actas Dermosifiliogr
  • [Language] spa
  • [Publication-type] Case Reports; English Abstract; Journal Article; Review
  • [Publication-country] Spain
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Antigens, Neoplasm; 0 / Biomarkers, Tumor; 0 / Immunoglobulin kappa-Chains; 0 / Immunosuppressive Agents; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 16
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10. Satoh K, Yoshida N, Imaizumi K, Yajima M, Wakui H, Sawada K, Komatsuda A: Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis. Am J Med Sci; 2009 Oct;338(4):334-5
NCI CPTAC Assay Portal. NCI CPTAC Assay Portal .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis.
  • A 73-year-old woman with rheumatoid arthritis had been treated with weekly low-dose methotrexate (MTX) for 5 years.
  • In situ hybridization identified Epstein-Barr virus latency-associated RNA expression in these cells.
  • She was diagnosed with Epstein-Barr virus-associated polymorphic lymphoproliferative disorder (LPD) due to immunodeficiency caused by MTX administration.
  • Cessation of MTX therapy led to complete regression of the tumor.
  • To our knowledge, this is the first case of spontaneous remission of MTX-associated gastric LPD after discontinuation of MTX therapy.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Arthritis, Rheumatoid / drug therapy. Lymphoproliferative Disorders / diagnosis. Methotrexate / adverse effects. Stomach Neoplasms / chemically induced
  • [MeSH-minor] Aged. Female. Humans. Treatment Outcome


11. Nagai S, Izutsu K, Watanabe T, Kurokawa M: Simultaneous appearance of methotrexate-associated lymphoproliferative disorder and tuberculous meningitis demonstrating the definitive role of immunosuppression. Ann Hematol; 2009 Jun;88(6):589-90
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Simultaneous appearance of methotrexate-associated lymphoproliferative disorder and tuberculous meningitis demonstrating the definitive role of immunosuppression.
  • [MeSH-major] Immunosuppression. Lymphoproliferative Disorders / chemically induced. Lymphoproliferative Disorders / complications. Methotrexate / adverse effects. Tuberculosis, Meningeal / complications
  • [MeSH-minor] Aged. Arthritis, Rheumatoid / drug therapy. Arthritis, Rheumatoid / immunology. Female. Humans

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  • (PMID = 18839171.001).
  • [ISSN] 1432-0584
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] Germany
  • [Chemical-registry-number] YL5FZ2Y5U1 / Methotrexate
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12. Hsiao SC, Ichinohasama R, Lin SH, Liao YL, Chang ST, Cho CY, Chuang SS: EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate. Pathol Res Pract; 2009;205(1):43-9
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate.
  • Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid proliferation or lymphoma in a patient immunosuppressed with MTX, which is usually administered for treating autoimmune diseases.
  • The patient developed EBV-positive MTX-LPD at nodal and extranodal sites.
  • These findings indicated a type III latency infection of EBV.
  • [MeSH-major] Dermatologic Agents / adverse effects. Epstein-Barr Virus Infections / chemically induced. Immunosuppressive Agents / adverse effects. Lymphoma, Large B-Cell, Diffuse / chemically induced. Lymphoma, Large B-Cell, Diffuse / virology. Methotrexate / adverse effects. Psoriasis / drug therapy

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  • (PMID = 18951733.001).
  • [ISSN] 0344-0338
  • [Journal-full-title] Pathology, research and practice
  • [ISO-abbreviation] Pathol. Res. Pract.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Dermatologic Agents; 0 / Immunosuppressive Agents; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 22
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13. Nemoto Y, Taniguchi A, Kamioka M, Nakaoka Y, Hiroi M, Yokoyama A, Enzan H, Daibata M: Epstein-Barr virus-infected subcutaneous panniculitis-like T-cell lymphoma associated with methotrexate treatment. Int J Hematol; 2010 Sep;92(2):364-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Epstein-Barr virus-infected subcutaneous panniculitis-like T-cell lymphoma associated with methotrexate treatment.
  • Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid proliferation or lymphoma in patients treated with MTX.
  • The patient, who had been on MTX therapy for RA, manifested high fever and lumbago.
  • Biopsy of the inguinal nodule showed profuse infiltration of CD8(+) T-cell lymphoma cells in the subcutaneous adipose tissues.
  • Studies have reported that most MTX-LPDs are B-cell type lymphomas and Hodgkin lymphoma.
  • Our case emphasizes the importance of clinical and virological characterization of MTX-associated SPTCL.
  • [MeSH-major] Epstein-Barr Virus Infections. Methotrexate / adverse effects
  • [MeSH-minor] Arthritis, Rheumatoid / complications. Arthritis, Rheumatoid / drug therapy. Humans. Lymphoma, T-Cell / chemically induced. Lymphoma, T-Cell / virology. Male. Middle Aged. Panniculitis / chemically induced. Panniculitis / virology

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  • [Cites] J Am Acad Dermatol. 1998 Nov;39(5 Pt 1):721-36 [9810888.001]
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  • (PMID = 20665252.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] YL5FZ2Y5U1 / Methotrexate; Subcutaneous panniculitis-like T-cell lymphoma
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14. Moseley AC, Lindsley HB, Skikne BS, Tawfik O: Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's disease. J Rheumatol; 2000 Mar;27(3):810-3
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's disease.
  • We describe a case of nodular sclerosing Hodgkin's disease (NSHD) developing in a 61-year-old woman with seropositive rheumatoid arthritis treated with oral methotrexate (MTX) 5 to 15 mg/week for 5 years.
  • Computed tomography (CT) of the abdomen revealed splenomegaly and marked abdominal and retroperitoneal lymphadenopathy.
  • Patients with apparently reversible MTX associated lymphoproliferative disorder require periodic monitoring for asymptomatic development of malignant lymphoma.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Hodgkin Disease / etiology. Lymphoproliferative Disorders / chemically induced. Lymphoproliferative Disorders / complications. Methotrexate / adverse effects
  • [MeSH-minor] Arthritis, Rheumatoid / drug therapy. Disease Progression. Female. Herpesvirus 4, Human / physiology. Humans. Middle Aged. Tomography, X-Ray Computed. Virus Activation

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  • (PMID = 10743830.001).
  • [ISSN] 0315-162X
  • [Journal-full-title] The Journal of rheumatology
  • [ISO-abbreviation] J. Rheumatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] CANADA
  • [Chemical-registry-number] 0 / Antirheumatic Agents; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 16
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15. Vincent S, Slease RB, Rocca PV: Epstein-Barr virus-associated lymphoproliferative disorder in a patient with rheumatoid arthritis on methotrexate and rofecoxib: idiosyncratic reaction or pharmacogenetics? Del Med J; 2002 Dec;74(12):469-73
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Epstein-Barr virus-associated lymphoproliferative disorder in a patient with rheumatoid arthritis on methotrexate and rofecoxib: idiosyncratic reaction or pharmacogenetics?
  • Rheumatoid arthritis (RA) is an autoimmune disease associated with altered immunoregulation and resulting in a deforming polyarthritis.
  • Methotrexate (MTX) is a commonly used second line agent for RA, and there have been several recent reports of Epstein-Barr virus (EBV)-associated polyclonal B cell lymphoproliferative disorder in MTX-treated RA patients.
  • She developed a febrile illness associated with severe pancytopenia and leukocytoclastic vasculitic rash followed by diffuse adenopathy, with serologic and pathologic evidence of EBV infection.
  • Previous studies have demonstrated the interaction of MTX and a variety of non-steroidal, anti-inflammatory drugs (NSAIDs) with various clinical manifestations including acute renal failure, pancytopenia, vomiting, diarrhea, elevated liver transaminases, jaundice, mucosal ulcerations, and pyrexia.
  • We hypothesize that decreased renal elimination of MTX induced by the COX-2 inhibitor resulted in enhanced hematopoietic toxicity and immunosuppression causing the EBV-associated lymphoproliferative disease.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Arthritis, Rheumatoid / drug therapy. Cyclooxygenase Inhibitors / adverse effects. Epstein-Barr Virus Infections / chemically induced. Lactones / adverse effects. Lymphoproliferative Disorders / chemically induced. Methotrexate / adverse effects. Sulfones / adverse effects
  • [MeSH-minor] Adult. Drug Interactions. Female. Humans

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  • (PMID = 15595320.001).
  • [ISSN] 0011-7781
  • [Journal-full-title] Delaware medical journal
  • [ISO-abbreviation] Del Med J
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antirheumatic Agents; 0 / Cyclooxygenase Inhibitors; 0 / Lactones; 0 / Sulfones; 0QTW8Z7MCR / rofecoxib; YL5FZ2Y5U1 / Methotrexate
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16. Hatachi S, Kunitomi A, Aozasa K, Yagita M: CD8(+) T-cell lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis during methotrexate therapy. Mod Rheumatol; 2010 Oct;20(5):500-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] CD8(+) T-cell lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis during methotrexate therapy.
  • A 75-year-old woman with rheumatoid arthritis (RA) who was receiving methotrexate (MTX) therapy developed Epstein-Barr virus (EBV)-associated CD8(+) T-cell lymphoproliferative disorder (LPD) and meningoencephalitis.
  • To our knowledge, this is the first report of CD8(+) T-cell LPD with EBV genome occurring during MTX therapy for RA.
  • EBV infection should be carefully monitored to assess severe EBV-associated complications.

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  • (PMID = 20437072.001).
  • [ISSN] 1439-7609
  • [Journal-full-title] Modern rheumatology
  • [ISO-abbreviation] Mod Rheumatol
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antirheumatic Agents; 0 / Antiviral Agents; X4HES1O11F / Acyclovir; X4W7ZR7023 / Methylprednisolone; YL5FZ2Y5U1 / Methotrexate
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17. Van Haarlem SW, Verpalen MC, Van Gorp JM, Hoekstra JB, Van Den Bosch JM: An Epstein-Barr virus-associated pulmonary lymphoproliferative disorder as complication of immunosuppression. Neth J Med; 2000 Oct;57(4):165-8
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] An Epstein-Barr virus-associated pulmonary lymphoproliferative disorder as complication of immunosuppression.
  • Inherited or acquired immunodeficiencies as well as autoimmune diseases treated with cytotoxic drugs are associated with an increased incidence of lymphoma.
  • Non-Hodgkin's lymphomas that occur in the context of drug-induced immunosuppression, acquired or congenital immunodeficiency, are frequently associated with Epstein-Barr virus infection.
  • This report describes the occurrence of an Epstein-Barr virus associated pulmonary B cell lymphoma in a patient with longstanding rheumatoid arthritis treated with methotrexate.
  • [MeSH-major] Arthritis, Rheumatoid / drug therapy. Epstein-Barr Virus Infections / complications. Immunocompromised Host. Immunosuppressive Agents / adverse effects. Lung Neoplasms / chemically induced. Lung Neoplasms / virology. Lymphoma, B-Cell / chemically induced. Lymphoma, B-Cell / virology. Methotrexate / adverse effects
  • [MeSH-minor] Biopsy, Needle. Humans. Male. Middle Aged. Risk Factors. Tomography, X-Ray Computed

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  • (PMID = 11006493.001).
  • [ISSN] 0300-2977
  • [Journal-full-title] The Netherlands journal of medicine
  • [ISO-abbreviation] Neth J Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] NETHERLANDS
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; YL5FZ2Y5U1 / Methotrexate
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18. Komatsuda A, Wakui H, Nimura T, Sawada K: Reversible infliximab-related lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis. Mod Rheumatol; 2008;18(3):315-8
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Reversible infliximab-related lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis.
  • A 63-year-old woman with active rheumatoid arthritis (RA) had been treated with methotrexate and prednisolone.
  • She developed cervical lymph node swelling 30 months after the initiation of infliximab therapy.
  • A computed tomography revealed cervical and mediastinal lymph node swelling and multiple nodules (up to 13 mm in diameter) in the lungs.
  • She was diagnosed as having EBV-associated lymphoproliferative disorder (LPD).
  • Immunodeficiency-associated LPD related with infliximab therapy was considered.
  • Cessation of infliximab therapy only led to dramatic regression of LPD.
  • This case illustrates that EBV-associated LPDs can occur as part of infliximab adverse effects in patients with RA.

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  • (PMID = 18368468.001).
  • [ISSN] 1439-7595
  • [Journal-full-title] Modern rheumatology
  • [ISO-abbreviation] Mod Rheumatol
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antirheumatic Agents; 0 / Glucocorticoids; 9PHQ9Y1OLM / Prednisolone; B72HH48FLU / Infliximab; YL5FZ2Y5U1 / Methotrexate
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19. Kojima M, Itoh H, Hirabayashi K, Igarashi S, Tamaki Y, Murayama K, Ogura H, Saitoh R, Kashiwabara K, Takimoto J, Masawa N, Nakamura S: Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases. Pathol Res Pract; 2006;202(9):679-85
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases.
  • We conducted clinicopathological and immunohistochemical analyses to investigate the prevalence of Epstein-Barr virus (EBV) among 13 cases with methotrexate (MTX)-associated lymphoproliferative disorder (LPD).
  • All 13 patients had received low dose MTX therapy for 1-13 years before the onset of LPD (mean: 5.8 years).
  • The present study suggests that EBV- associated non-Hodgkin lymphomas comprise only a portion of all non-Hodgkin lymphomas among MTX-associated LPDs.
  • [MeSH-major] Antimetabolites, Antineoplastic / adverse effects. Epstein-Barr Virus Infections / epidemiology. Lymphoproliferative Disorders / chemically induced. Lymphoproliferative Disorders / virology. Methotrexate / adverse effects
  • [MeSH-minor] Aged. Arthritis, Rheumatoid / drug therapy. Female. Humans. Immunohistochemistry. In Situ Hybridization. Male. Middle Aged. Prevalence. RNA, Viral / isolation & purification

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  • (PMID = 16859835.001).
  • [ISSN] 0344-0338
  • [Journal-full-title] Pathology, research and practice
  • [ISO-abbreviation] Pathol. Res. Pract.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / RNA, Viral; YL5FZ2Y5U1 / Methotrexate
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20. Tournadre A, D'Incan M, Dubost JJ, Franck F, Déchelotte P, Souteyrand P, Soubrier M: Cutaneous lymphoma associated with Epstein-Barr virus infection in 2 patients treated with methotrexate. Mayo Clin Proc; 2001 Aug;76(8):845-8
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Cutaneous lymphoma associated with Epstein-Barr virus infection in 2 patients treated with methotrexate.
  • Whether patients with rheumatoid arthritis (RA) have an increased risk of developing non-Hodgkin lymphoma is controversial, and opinions differ on the possible role of methotrexate in the occurrence of lymphomas in patients with RA.
  • We report 1 T-cell lymphoma and 1 B-cell lymphoma restricted to the skin associated with Epstein-Barr virus infection that healed completely and spontaneously after discontinuation of methotrexate in a man with RA and a woman with dermatomyositis.
  • After discontinuation of methotrexate, the cutaneous lesions disappeared completely in 15 days without recurrence.
  • Discontinuation of methotrexate is necessary in patients with RA or dermatomyositis who have a lymphoproliferative disorder, and a follow-up period of several weeks should be observed before specific therapy is initiated.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Burkitt Lymphoma / virology. Dermatologic Agents / adverse effects. Epstein-Barr Virus Infections / complications. Herpesvirus 4, Human / isolation & purification. Immunosuppressive Agents / adverse effects. Lymphoma, T-Cell, Cutaneous / virology. Methotrexate / adverse effects. Skin / pathology
  • [MeSH-minor] Aged. Arthritis, Rheumatoid / drug therapy. Dermatomyositis / drug therapy. Female. Humans. In Situ Hybridization. Male. Middle Aged. RNA, Viral / isolation & purification

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  • (PMID = 11499826.001).
  • [ISSN] 0025-6196
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antirheumatic Agents; 0 / Dermatologic Agents; 0 / Immunosuppressive Agents; 0 / RNA, Viral; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 18
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21. Jacobs SA, Vidnovic N, Patel H, Soma LA, Chang Y, Bass N, Swerdlow SH: Durable remission of HIV-negative, Kaposi's sarcoma herpes virus-associated multicentric Castleman disease in patient with rheumatoid arthritis treated with methotrexate. Clin Rheumatol; 2007 Jul;26(7):1148-50
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  • [Title] Durable remission of HIV-negative, Kaposi's sarcoma herpes virus-associated multicentric Castleman disease in patient with rheumatoid arthritis treated with methotrexate.
  • Multicentric Castleman disease (MCD) is a nonneoplastic lymphoproliferative disorder that has a poor prognosis.
  • Optimal treatment is unknown.
  • In this study, we report a patient with rheumatoid arthritis diagnosed with Kaposi's sarcoma herpesvirus-(KSHV, human herpesvirus-8) associated MCD that showed expression of viral IL-6.
  • Treatment with methotrexate (MTX) resulted in a complete remission of her disease lasting for 54+ months.
  • Multiple studies have suggested that MCD and rheumatoid arthritis are associated with overexpression of the growth-promoting cytokine interleukin-6 (IL-6), and that MTX downregulates the production of this cytokine in vivo.
  • [MeSH-major] Arthritis, Rheumatoid / drug therapy. Giant Lymph Node Hyperplasia / drug therapy. Herpesvirus 8, Human / isolation & purification. Immunosuppressive Agents / therapeutic use. Methotrexate / therapeutic use. Sarcoma, Kaposi / drug therapy


22. Boulanger E, Agbalika F, Maarek O, Daniel MT, Grollet L, Molina JM, Sigaux F, Oksenhendler E: A clinical, molecular and cytogenetic study of 12 cases of human herpesvirus 8 associated primary effusion lymphoma in HIV-infected patients. Hematol J; 2001;2(3):172-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A clinical, molecular and cytogenetic study of 12 cases of human herpesvirus 8 associated primary effusion lymphoma in HIV-infected patients.
  • INTRODUCTION: Primary effusion lymphoma is a rare type of B-cell lymphoproliferative disorder which is mainly observed in patients with HIV infection.
  • PATIENTS AND METHODS: : Twelve HIV-infected patients with serous effusions containing large HHV8(+) lymphomatous cells were extensively evaluated to disclose associated visceral involvement.
  • Three patients are in complete remission at 28, 53 and 55 months after high-dose chemotherapy (n = 1), cidofovir and alpha-interferon combination therapy (n = 1), and antiretroviral therapy alone (n = 1).
  • CONCLUSION: The clinical and molecular pattern, as well as the response to therapy suggest that primary effusion lymphoma represents an heterogenous type of virus-induced B-cell lymphoproliferative disorder, sharing pathophysiological features with that induced by the Epstein-Barr virus and occurring in immunocompromised patients.

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  • (PMID = 11920242.001).
  • [ISSN] 1466-4860
  • [Journal-full-title] The hematology journal : the official journal of the European Haematology Association
  • [ISO-abbreviation] Hematol. J.
  • [Language] ENG
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-HIV Agents; 0 / Antiviral Agents; 0 / Interferon-alpha; 0 / Organophosphonates; 0 / Organophosphorus Compounds; 11056-06-7 / Bleomycin; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 80168379AG / Doxorubicin; 8J337D1HZY / Cytosine; 8N3DW7272P / Cyclophosphamide; JIL713Q00N / cidofovir; RSA8KO39WH / Vindesine; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 37
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23. Bhargava R, Barbashina V, Filippa DA, Teruya-Feldstein J: Epstein-Barr virus positive large B-cell lymphoma arising in a patient previously treated with Cladribine for hairy cell leukemia. Leuk Lymphoma; 2004 May;45(5):1043-8
Hazardous Substances Data Bank. CLADRIBINE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • We describe the case of a patient treated with 2-chloro-2'-deoxyadenosine, CdA or Cladribine for hairy cell leukemia who subsequently developed an Epstein Barr virus (EBV)-positive polymorphous large B-cell lymphoma (p-LBCL).
  • The time interval between Cladribine therapy and development of p-BCL was 11 months and morphologically resembled an EBV-positive post transplant lymphoproliferative disorder (PTLD).
  • Unlike most methotrexate-related lymphoproliferative disorders (LPDs), which undergo spontaneous remission after discontinuation of therapy, LPDs secondary to purine analogs often fails to resolve after discontinuation of therapy and requires additional therapy.
  • Our patient was treated with rituximab following the diagnosis of p-LBCL, with the goal of improving the pancytopenia to permit chemotherapy.
  • However, the patient failed to show any dramatic improvements in counts, developed systemic symptoms and progressive ascites.
  • Cladribine is a potent immunosuppressive agent and should be included with the list of immunosuppressive agents that may be associated with EBV-related B-cell lymphoproliferative disorders.

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  • (PMID = 15291365.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 47M74X9YT5 / Cladribine
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24. Mahé E, Descamps V, Grossin M, Fraitag S, Crickx B: CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab. Br J Dermatol; 2003 Jul;149(1):170-3
Hazardous Substances Data Bank. CYCLOSPORIN A .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies.
  • These lymphomas are mainly B-cell nonHodgkin's lymphomas associated with Epstein-Barr virus.
  • Most cases concern classical immunosuppressive treatments including ciclosporin and methotrexate.
  • A relationship between the new antitumour necrosis factor (TNF)-alpha agents and lymphoproliferative malignancies is debated.
  • Patients with psoriasis on immunosuppressive therapies, mainly ciclosporin, are considered to have a low risk of developing lymphoid proliferation.
  • We report a patient with erythrodermic psoriasis treated with ciclosporin and infliximab who developed a CD30+ T-cell lymphoma.
  • This lymphoma regressed after stopping these treatments.
  • In this case, the anti-TNF-alpha agent may have played a role in association with ciclosporin in the development of the lymphoproliferative disorder.
  • Whereas the combination of anti-TNF-alpha therapies with methotrexate has been well studied, their combination with ciclosporin has been evaluated only in a few patients.
  • Psoriatic patients who may require anti-TNF-alpha treatment have often been or will be treated with ciclosporin.
  • [MeSH-major] Antibodies, Monoclonal / adverse effects. Cyclosporine / adverse effects. Immunosuppressive Agents / adverse effects. Lymphoma, Large-Cell, Anaplastic / chemically induced. Psoriasis / drug therapy. Skin Neoplasms / chemically induced
  • [MeSH-minor] Dermatologic Agents / adverse effects. Drug Therapy, Combination. Humans. Infliximab. Male. Middle Aged

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  • (PMID = 12890213.001).
  • [ISSN] 0007-0963
  • [Journal-full-title] The British journal of dermatology
  • [ISO-abbreviation] Br. J. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Dermatologic Agents; 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine; B72HH48FLU / Infliximab
  • [Number-of-references] 17
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25. Kumar N, Sandroni P, Steensma DP, Luthra HS, Habermann TM: Polyradiculopathy due to methotrexate-induced ebv-associated lymphoproliferative disorder. Neurology; 2008 Nov 11;71(20):1644-5
Hazardous Substances Data Bank. METHOTREXATE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Polyradiculopathy due to methotrexate-induced ebv-associated lymphoproliferative disorder.
  • [MeSH-major] Antirheumatic Agents / adverse effects. Herpesvirus 4, Human / pathogenicity. Lymphoproliferative Disorders / etiology. Methotrexate / adverse effects. Polyradiculopathy / etiology
  • [MeSH-minor] Arthritis, Rheumatoid / drug therapy. Female. Humans. Middle Aged

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  • (PMID = 19001256.001).
  • [ISSN] 1526-632X
  • [Journal-full-title] Neurology
  • [ISO-abbreviation] Neurology
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antirheumatic Agents; YL5FZ2Y5U1 / Methotrexate
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