Decreases in levels of serum fibronectin predict the severity of vascular leak syndrome in patients treated with ricin A chain-containing immunotoxins

Roxana Baluna, Edward A. Sausville, Marvin J. Stone, Mary Alice Stetler-Stevenson, Jonathan W. Uhr, Ellen S. Vitetta

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Abstract

The major dose-limiting adverse effect of ricin A chain-containing immunotoxin (IT) therapy is vascular leak syndrome (VLS). Since plasma fibronectin (Fn) plays a role in maintaining microcirculatory integrity and since the gradient between plasma and tissue Fn can be altered in various pathological situations, we determined whether the administration of IT-ricin A chain to patients resulted in changes in the levels of serum Fn and, if so, whether these changes correlated with the severity of VLS. We also measured the serum levels of tumor necrosis factor α (TNFα), a proinflammatory cytokine which has been implicated in tissue damage and in interleukin 2-mediated VLS. Our results indicate that the most severe manifestations of VLS were associated with the highest pretreatment levels of Fn, the largest decreases in Fn immediately after starting IT therapy, increases in the levels of serum TNFα, higher concentrations of circulating IT, and the lowest numbers of circulating tumor cells. These parameters should, therefore, be useful for predicting which patients will have severe VLS.

Original languageEnglish (US)
Pages (from-to)1705-1712
Number of pages8
JournalClinical Cancer Research
Volume2
Issue number10
StatePublished - Oct 1996

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Ricin
Immunotoxins
Fibronectins
Blood Vessels
Serum
Tumor Necrosis Factor-alpha
Circulating Neoplastic Cells
Interleukin-2
Cytokines
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Decreases in levels of serum fibronectin predict the severity of vascular leak syndrome in patients treated with ricin A chain-containing immunotoxins. / Baluna, Roxana; Sausville, Edward A.; Stone, Marvin J.; Stetler-Stevenson, Mary Alice; Uhr, Jonathan W.; Vitetta, Ellen S.

In: Clinical Cancer Research, Vol. 2, No. 10, 10.1996, p. 1705-1712.

Research output: Contribution to journalArticle

Baluna, Roxana ; Sausville, Edward A. ; Stone, Marvin J. ; Stetler-Stevenson, Mary Alice ; Uhr, Jonathan W. ; Vitetta, Ellen S. / Decreases in levels of serum fibronectin predict the severity of vascular leak syndrome in patients treated with ricin A chain-containing immunotoxins. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 10. pp. 1705-1712.
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