utropenia after the third week of treatment and this may continue for up to 10days after the last dose. Subsequently, the neutrophil count usually rapidly returns to normal. Severe neutropenia appears to be related to dosage and usually occurs only in patients who have received a total dosage of 6.5mg/kg or more in one course of therapy with continuous dosing. About one quarter of all patients receiving the continuous-dose schedule, and one third of those receiving this dosage in 8weeks or less may be expected to develop severe neutropenia.
While it is not necessary to discontinue chlorambucil at the first evidence of a fall in neutrophil count, it must be remembered that the fall may continue for 10days after the last dose, and that as the total dose approaches 6.5mg/kg, there is a risk of causing irreversible bone marrow damage. The dose of chlorambucil should be decreased if leukocyte or platelet counts fall below normal values and should be discontinued for more severe depression.
Chlorambucil should not be given at full dosages before 4weeks after a full course of radiation therapy or chemotherapy because of the vulnerability of the bone marrow to damage under these conditions. If the pretherapy leukocyte or platelet counts are depressed from bone marrow disease process prior to institution of therapy, the treatment should be instituted at a reduced dosage.
Persistently low neutrophil and platelet counts or peripheral lymphocytosis suggest bone marrow infiltration. If confirmed by bone marrow examination, the daily dosage of chlorambucil should not exceed 0.1mg/kg. Chlorambucil appears to be relatively free from gastrointestinal side effects or other evidence of toxicity apart from the bone marrow depressant action. In humans, single oral doses of 20mg or more may produce nausea and vomiting.
Children with nephrotic syndrome and patients receiving high pulse doses of chlorambucil may have an increased risk of seizures. As with any potentially epileptogenic drug, caution should be exercised when administering chlorambucil to patients with a history of seizure disorder or head trauma, or who are receiving other potentially epileptogenic drugs.
Administration of live vaccines to immunocompromised patients should be avoided.
Information for Patients
Patients should be informed that the major toxicities of chlorambucil are related to hypersensitivity, drug fever, myelosuppression, hepatotoxicity, infertility, seizures, gastrointestinal toxicity, and secondary malignancies. Patients should never be allowed to take the drug without medical supervision and should consult their physician if they experience skin rash, bleeding, fever, jaundice, persistent cough, seizures, nausea, vomiting, amenorrhea, or unusual lumps/masses. Women of childbearing potential should be advised to avoid becoming pregnant.
Laboratory Tests
Patients must be followed carefully to avoid life-endangering damage to the bone marrow during treatment. Weekly examination of the blood should be made to determine hemoglobin levels, total and differential leukocyte counts, and quantitative platelet counts. Also, during the first 3 to 6weeks of therapy, it is recommended that white blood cell counts be made 3 or 4days after each of the weekly complete blood counts. Galton et al have suggested that in following patients it is helpful to plot the blood counts on a chart at the same time that body weight, temperature, spleen size, etc., are recorded. It is consi
