Chromosome abnormalities from cyclophosphamide therapy in rheumatoid arthritis and progressive systemic sclerosis (scleroderma)

Tolchin, Sanford F.; Winkelstein, Alan; Rodnan, Gerald P.; Pan, Sylvia F.; Nankin, Howard R.

doi:10.1002/art.1780170406

Cited by 41 publications

(5 citation statements)

References 23 publications

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“…In this regard, therapy with cyclophosphamide leads to an increased incidence of chromosome aberrations in lymphocytes (18) including those associated with reproductive nonviability (19). This prolonged inhibition of proliferative responses may be an important factor in the sustained immunosuppressive activity of cyclophospamide (9,16 It is noteworthy that PPD-sensitive cells surviving administration of cyclophosphamide can elaborate this lymphokine but are markedly suppressed in their capacity to proliferate.…”

Section: Discussionmentioning

confidence: 99%

Effects of cytotoxic immunosuppressants on tuberculin-sensitive lymphocytes in guinea pigs.

Winkelstein¹

1975

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

Effects of cytotoxic immunosuppressants on tuberculin-sensitive lymphocytes in guinea pigs.

Winkelstein¹

1975

J. Clin. Invest.

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“…had been treated with immunosuppressive drugs, some of which have been shown to induce chromosome aberrations [45]. (3) The possibility that biological agents such as viruses were implicated in the production of chromosome damage cannot be exluded with certainty.…”

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confidence: 99%

Chromosomal Breakage in Systemic Sclerosis and Related Disorders

Emerit¹

1976

Dermatology

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Chromosome aberrations such as gaps and breaks of one or both chromatids, acentric fragments, dicentrics, ring chromosomes and other abnormal chromosomes are observed in lymphocyte and fibroblast cultures as well as in direct bone marrow preparations from patients with systemic sclerosis. A serum factor producing chromosome breaks in mitoses from healthy donors was observed in 37 of 42 scleroderma patients. The biochemical nature of this breakage factor is still undefined. Increased breakage is also noted in a high percentage of healthy family members of scleroderma patients. It is also a common feature of related disorders such as lupus erythematosus, dermatomyositis, periarteritis nodosa and rheumatoid arthritis. An increase in chromosome breaks and rearrangements is also present in NZB mice developing spontaneously an autoimmune disorder that has been extensively studied by workers interested in lupus erythematosus. The similarity of the cytogenetic findings provides the opportunity to use these mice as an experimental model to investigate relationships between immunological perturbations and chromosomal aberrations.

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“…explanation for the development of malignancy in the immunosuppressive drug-treated patient is not clear. Patients with rheumatoid arthritis show an appreciable increase in chromosomal abnormalities during therapy with cyclophosphamide (Tolchin et al, 1974) and it is possible that mutant cells are not properly recognized and destroyed as a result of defects in the immunosurveillance mechanism (Burnet, 1967). The interpretation that the present patient developed a tumour related to his immunosuppressive therapy is conjectural but the fact remains that tumour development should be considered as a potential hazard of cyclophosphamide therapy.…”

Section: Discussionmentioning

confidence: 99%