Pathology of high dose intermittent cyclophosphamide therapy.

Pathologic changes induced by high dose intermittent cyclophosphamide therapy are described in 39 patients with solid tumors, lymphohematopoietic malignant disease, and bone marrow transplants. Patients receiving 50 to 120 mg. per kg. daily for one to four days showed transmural bladder injury affecting all component tissue; toxic vasculitis involving small arteries, capillaries, and venules; and interstitial, myocardial, and vascular changes in the heart. Myocardial necrosis with heart failure was the dose limiting factor of very high dose therapy. Patients receiving 15 to 30 mg. per kg. for four days showed variable degrees of bladder injury limited to the mucosa and lamina propria and vascular changes consisting only of telangiectasia. Both groups showed atypia of transitional urinary and esophageal epithelia as well as of mesenchymal cells in the lamina propria of the bladder, persistent and total ablation of spermatogenesis, and long lasting absence of ovarian follicular maturation. Bone marrow hypoplasia and lymphoid depletion developing after cyclophosphamide therapy completely disappeared an average of 3.5 weeks after the last dose.