Chlorambucil is indicated for the treatment of several cancers of the blood and lymphatic system. It is commonly used in the management of Hodgkin Lymphoma, certain types of Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia (CLL), and Waldenström Macroglobulinemia.

Chlorambucil is an anticancer agent that works by disrupting the replication of DNA and causing damage to the DNA within cells. This DNA damage stops the cell cycle and can trigger programmed cell death (apoptosis). The process involves the accumulation of the p53 protein in the cell and activation of Bax, a protein that promotes apoptosis.

Chlorambucil acts as an alkylating agent that attaches alkyl groups to DNA and forms cross-links within the DNA strands. These actions damage DNA throughout all phases of the cell cycle through several mechanisms:

• Attachment of alkyl groups to DNA bases, which leads repair enzymes to break DNA while trying to replace the damaged bases, ultimately blocking DNA and RNA synthesis.
• Formation of DNA cross-links that prevent the DNA strands from separating, thereby stopping DNA replication and transcription.
• Causing incorrect pairing of nucleotides, which may lead to genetic mutations.

Although these mechanisms are known, the exact process by which Chlorambucil ultimately destroys tumor cells is not yet fully understood.

Hodgkin's disease: 200 mcg/kg/day for 4-8 wk.

Non-Hodgkin's lymphoma: 100-200 mcg/kg/day for 4-8 wk. Maintenance: Reduced daily dosage of intermittent courses of treatment.

Chronic lymphocytic leukaemia: Initially, 150 mcg/kg/day until the total leukocyte count falls to 10,000 microliter. Treatment may be resumed 4 wk after at a dose of 100 mcg/kg/day.

Waldenstrom's macroglobulinaemia: Starting dose of 6-12 mg daily until leucopenia occurs followed by 2-8 mg daily.

Should be taken on an empty stomach: Ensure adequate hydration. Swallow whole, do not chew/crush.

Chlorambucil should not be used during the first trimester of pregnancy or while breastfeeding, as it may pose significant risks to the fetus or nursing infant.

Bone marrow suppression, seizures in children with nephrotic syndrome, nausea, vomiting, diarrhea, and oral ulceration. Rarely, irreversible bone marrow failure, hypersensitivity reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures, movement disorders, interstitial pulmonary fibrosis, interstitial pneumonia, hepatotoxicity, jaundice, sterile cystitis, and drug-induced fever may occur.

Pregnancy Category D: There is clear evidence of risk to the human fetus; however, the potential benefits of using the drug in pregnant women may outweigh the risks in certain situations (e.g., life-threatening conditions or serious diseases where safer alternatives are not effective or unavailable).

Regular monitoring of full blood count (FBC) is required. Bone marrow suppression may be reversible if the drug is discontinued early. This drug should not be administered to patients who have recently received radiotherapy or chemotherapy. In cases of lymphocytic infiltration of the bone marrow or hypoplastic bone marrow, the maximum daily dose should not exceed 0.1 mg/kg. Use with caution in children with nephrotic syndrome, patients receiving high-dose pulse regimens, or those with a history of seizure disorders. Caution is also advised in patients with renal or hepatic impairment. Adequate contraceptive measures should be ensured during treatment. Avoid use during pregnancy unless clearly necessary.

Cytotoxic Chemotherapy