Malignancy following treatment of rheumatoid arthritis with cyclophosphamide

Baker, Gary L.; Kahl, Leslie E.; Zee, Benny; Stolzer, Bertrand L.; Agarwal, Abhishek; Medsger, Thomas A.

doi:10.1016/0002-9343(87)90490-6

Cited by 250 publications

(112 citation statements)

References 32 publications

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“…In both patients with SLE and murine models, treatment with immunosuppressive agents such as corticosteroids or cyclophosphamide can reduce the progression of lupus nephritis and prolong survival (6 -9). However, these agents have severe potential side effects, including increased susceptibility to infections (10 -12) and the development of malignant tumors (13). Therefore, the development of new drugs with few side effects is needed.…”

mentioning

confidence: 99%

Retinoic Acid Reduces Autoimmune Renal Injury and Increases Survival in NZB/W F1 Mice

Kinoshita

Yoo

Nozaki

et al. 2003

The Journal of Immunology

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Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent antiproliferative and anti-inflammatory properties. Recently, retinoic acids were reported to inhibit Th1 cytokine production. We investigated the effects of retinoic acid on lupus nephritis in a model of NZB/NZW F1 (NZB/W F1) mice. Three-month-old NZB/W F1 mice were separated into two groups: one treated with all-trans-retinoic acid (ATRA; 0.5 mg i.p., three times weekly for 7 mo) and one with saline as a control. Compared with controls, ATRA-treated mice survived longer and exhibited a significant reduction of proteinuria, renal pathological findings including glomerular IgG deposits, and serum anti-DNA Abs. Splenomegaly was less marked in the treated mice than in controls. Transcripts encoding IFN-γ, IL-2, and IL-10 in splenic CD4+ T cells were significantly reduced in treated mice compared with controls. We conclude that treatment with ATRA in SLE-prone NZB/W F1 mice significantly alleviates autoimmune renal disorder and prolongs survival; this may thus represent a novel approach to the treatment of patients with lupus nephritis.

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mentioning

confidence: 99%

Retinoic Acid Reduces Autoimmune Renal Injury and Increases Survival in NZB/W F1 Mice

Kinoshita

Yoo

Nozaki

et al. 2003

The Journal of Immunology

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“…At doses used for lupus nephritis in humans, CTX therapy results in a reduction in peripheral lymphocytes (12) and an increased risk of some infections (13,14). In addition, prolonged therapy commonly results in ovarian failure (15), azoospermia (16), and an increased rate of various malignancies (17). In contrast, CTLA4Ig does not reduce lymphocyte counts in B/W mice (11).…”

mentioning

confidence: 99%

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

Daikh

Wofsy

2001

The Journal of Immunology

188

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Cyclophosphamide (CTX) prevents progression of nephritis and prolongs survival in (NZB × NZW)F1 (B/W) mice and is used to treat humans with lupus nephritis. To compare the efficacy of CTLA4Ig with CTX and determine whether there is an incremental benefit to combining CTLA4Ig with CTX, we treated B/W mice with CTX, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all groups. In mice with advanced renal disease, treatment with both agents reduced proteinuria in 71% of mice, whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice treated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolonging survival of B/W mice with advanced nephritis. This striking reversal of proteinuria is unprecedented in animal models of SLE.

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“…No late complications (for example fertility disorders or increased risk of cancer) were taken into account [12,13].…”

Section: Methodsmentioning

confidence: 99%

The Safety of Intravenous Cyclophosphamide in the Treatment of Rheumatic Diseases

Woytala¹,

Morgiel²,

Łuczak³

et al. 2016

Adv Clin Exp Med

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Malignancy following treatment of rheumatoid arthritis with cyclophosphamide

Cited by 250 publications

References 32 publications

Retinoic Acid Reduces Autoimmune Renal Injury and Increases Survival in NZB/W F1 Mice

Retinoic Acid Reduces Autoimmune Renal Injury and Increases Survival in NZB/W F1 Mice

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

The Safety of Intravenous Cyclophosphamide in the Treatment of Rheumatic Diseases

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