Toxicities Of Alkylating Agents Bone Marrow Toxicity

The alkylating agents differ in their patterns of antitumor activity and in the sites and severity of their side effects. Most cause dose-limiting toxicity to bone marrow and intestinal mucosa. Most alkylating agents, including nitrogen mustard, melphalan, chlorambucil, cyclophosphamide, and ifosfamide, cause acute myelosuppression, with a nadir of the peripheral blood granulocyte count at 6-10 days and recovery in 14-21 days. Cyclophosphamide has lesser effects on peripheral blood platelet counts than do the other agents. Busulfan suppresses all blood elements, particularly stem cells, and may produce a prolonged and cumulative myelosuppression lasting months or even years. For this reason, it is used in preparation for allogeneic bone marrow transplantation. Carmustine and other chloroethylnitrosoureas cause delayed and prolonged suppression of both platelets and granulocytes, reaching a nadir 4-6 weeks after drug administration and reversing slowly thereafter. Both cellular and humoral immunity are suppressed by alkylating agents, which have been used to treat various autoimmune diseases. Immunosuppression is reversible at doses used in most anticancer protocols.

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