Toxicity

As Krumbhaar noted in 1919, poisoning caused by sulfur mustard is characterized by aplasia of bone marrow, dissolution of lymphoid tissue, and ulceration of the gastrointestinal tract.1 While the alkylating agents differ somewhat in spectrum of activity and severity of adverse effects, most exhibit toxicities similar to those observed with the original agent. These compounds are typically dose-limited by suppressive effects on the bone marrow. Myelosuppression often manifests acutely, with an onset of 6-10 days and recovery within 14-21 days.5 Some compounds, such as busul-fan and carmustine, exhibit a prolonged suppression of granulocytes and platelets, and for this reason are commonly used in stem cell transplant preparative regimens. Suppression of both cellular and humoral immunity occurs frequently. The rapidly dividing cells of the intestinal mucosa are particularly sensitive to the effects of alkylating agents, evidenced by mucositis and stomatitis. Specific organ toxicities, such as pulmonary fibrosis, have been reported with all alkylating agents. In addition, this entire class of compounds is associated with a high incidence of secondary malignancies, affecting up to 5% of exposed patients6 (Table 101.1).

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