Irreversible bone marrow failure with chlorambucil

Two cases of irreversible bone marrow failure are described, one with rheumatoid disease and one with systemic lupus erythematosus. Each case was associated with prior chlorambucil administration, effective in controlling the clinical manifestations (total dosage 398 and 1,764 mg respectively). The irreversibility of the bone marrow depression in the two cases presented stands in contrast to published assurances that chlorambucil-associated leukopenia is dose-related and readily reversible. The cases illustrate that chlorambucil therapy should not be continued after initial leukopenia, until peripheral counts or marrow cellularity has returned to normal. Titration of drug dosage and leukocyte count, as frequently employed with cyclophosphamide and other alkylating agents, must be presumed hazardous. Additional studies are needed to determine if irreversible bone marrow depression is dose-related or idiosyncratic.