The risk of neoplasms in patients treated with cyclosporine A

doi:10.1016/S0896-8411(89)80010-1

Journal of Autoimmunity

Volume 2, Issue 5, October 1989, Pages 723-731

https://doi.org/10.1016/S0896-8411(89)80010-1 Get rights and content

Immunosuppressive therapy (IT) carries inherent risks involving the occurrence of lymphoproliferative disorders and malignancies (MA). The most frequently observed neoplasms in organ-transplant (OT) recipients treated with cyclosporine A (Cy-A) involve the skin and the lymphoreticular system. A disproportionally high percentage of the skin MA are Kaposi's sarcoma. Compared with a normal, not-exposed population matched for age, sex and country; Cy-A-treated OT recipients have a 28-59-fold increased risk in patients receiving conventional immunosuppressive therapy (CIT) for OT. However, it appears that in Cy-A-treated patients the latency period for the development of lymphomas is shorter than in patients on CIT. Other MA are increased seven-fold in Cy-A-treated patients and between two- and six-fold in those receiving CIT. The overall incidence of all types of MA is increased two-fold for Cy-A recipients and between two- and four-fold for those on CIT. Therefore patients receiving IT should be carefully monitored with respect to the possible occurrence of neoplasms.

References (18)

HooverR. et al.
Risk of cancer in renal-transplant recipients
Lancet
(1973)
CalneR.Y. et al.
Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers
Lancet
(1979)
NagingtonJ. et al.
Cyclosporin A immunosuppression, Epstein-Barr antibody, and lymphoma
Lancet
(1980)
DummerJ.S. et al.
Epstein-Barr virus-induced lymphoma in a cardiac transplant recipient
Am. J. Med.
(1984)
StarzlT.E. et al.
Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy
Lancet
(1984)
HarwoodA.R. et al.
Kaposi's sarcoma in recipients of renal transplants
Am. J. Med.
(1979)
KinlenL.J. et al.
Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs
Br. Med. J.
(1979)
SheilA.G.R. et al.
Cancer and survival after cadaveric donor renal transplantation
Transplant. Proc.
(1979)
PennI. et al.
Development and incidence of cancer following cyclosporine therapy
Transplant. Proc.
(1986)

There are more references available in the full text version of this article.

Cited by (125)

Malignancy and rheumatoid arthritis: Epidemiology, risk factors and management
2018, Best Practice and Research: Clinical Rheumatology
Rheumatoid arthritis (RA) is a chronic inflammatory condition that can result in pain and functional disability. It is also associated with an increased occurrence of comorbidities, including an increased risk of certain cancers such as lung cancer and lymphoma. The aetiopathogenesis of this increased cancer risk is likely multifactorial and includes shared risk factors as well as chronic inflammation. There is also a concern that the treatment for RA itself may increase this risk further, particularly treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). This paper aims to review the evidence for the increased risk of cancer in RA as well as the latest evidence for the association between DMARDs and tumorigenesis. It also discusses the evidence for the management of patients with biologic DMARDs in the setting of existing cancer.
The use of cyclosporine in dermatology: Part II
2010, Journal of the American Academy of Dermatology
Citation Excerpt :
Potassium-sparing diuretics should also be avoided, because cyclosporine can increase serum potassium. The increased risk of malignancy associated with long-term cyclosporine use in transplant populations is well described.104,105 In this population, however, multiple immunosuppressive agents are frequently used in concert, resulting in higher levels of immunosuppression.
Cyclosporine is highly effective in the treatment of a multitude of dermatoses. Concern over its side effect profile has limited its use in dermatology. Adverse effects are, for the most part, dose dependent and related to duration of therapy. Using the recommended monitoring protocols results in a significant decrease in the incidence of cyclosporine-related toxicities. This article provides a comprehensive review of the pharmacokinetics of cyclosporine, potential drug interactions, adverse effects, and recommendations for monitoring in patients treated with cyclosporine. The use of cyclosporine in pregnancy and in the pediatric population is also addressed.
After completing this learning activity, participants should be familiar with the monitoring guidelines of cyclosporine, its contraindications, its possible drug interactions, its adverse effect profile, and its use in pregnancy and the childhood and adolescent populations.
CD4<sup>+</sup> T Cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation
2010, Cancer Cell
Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of tumorigenesis, but their role in oncogene inactivation-mediated tumor regression is unclear. Here, we show that an intact immune system, specifically CD4⁺ T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained tumor regression. Hence, CD4⁺ T cells are required for the remodeling of the tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction.
Safety Profile of IBD: Lymphoma Risks
2010, Medical Clinics of North America
Citation Excerpt :
As noted previously, the hypothesis that immunosuppression directly increases the risk of lymphoma is supported by observations of lymphoma regression with discontinuation of immunosuppression therapy. In the setting of organ transplantation and treatment of dermatologic disorders, complete remission of lymphomas associated with CsA treatment has occurred after dose reduction or discontinuation of the drug.50 MTX is a structural analogue of folic acid that inhibits the activity of dihydrofolate reductase, the enzyme responsible for converting folic acid to folate cofactors.
Safety Profile of IBD: Lymphoma Risks
2009, Gastroenterology Clinics of North America
Citation Excerpt :
A worldwide study of more than 5000 organ transplant patients found that 0.5% of men (10 men in total) and fewer than 0.1% of women (1 female patient) developed lymphoma, with differing latency periods from time of drug therapy to malignancy diagnosis for different transplant indications.50 This translated into an approximately 28-times higher risk of lymphoma in patients treated with CsA.50 A 5-year prospective cohort study of 1252 patients with psoriasis treated with CsA found no trend toward an increased incidence of malignancies over time within the cohort.51
Treatments for psoriasis and the risk of malignancy
2009, Journal of the American Academy of Dermatology
Citation Excerpt :
CsA, a calcineurin inhibitor, blocks production of interleukin 2 by activated CD4-positive T cells, thereby hindering the inflammatory process central to psoriasis for which CsA has been effectively used for more than two decades.48-50 In transplant patients, long-term treatment with CsA is associated with serious side effects, including risk of lymphoma, internal malignancies, skin cancers, and infections.51-54 In 1992, Koo et al55 reported the first case in the United States of lymphoma in a patient treated with CsA for a condition other than organ transplantation.
There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy.
Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab.
PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies—MTX, CsA, and MMF—may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor–α inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies.
The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor.
Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.

View all citing articles on Scopus

View full text

The risk of neoplasms in patients treated with cyclosporine A

Lancet

Lancet

Lancet

Am. J. Med.

Lancet

Am. J. Med.

Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs

Br. Med. J.

Cancer and survival after cadaveric donor renal transplantation

Transplant. Proc.

Development and incidence of cancer following cyclosporine therapy

Transplant. Proc.