Leukeran (Chlorambucil)

Chlorambucil is used in the management of lymphoid malignancies, targeting proliferating cancer cells.

• Chronic lymphocytic leukemia (CLL): administered as part of first‑line or salvage therapy to reduce leukemic cell burden and prolong progression‑free survival.
• Hodgkin's lymphoma: incorporated into multi‑agent protocols to achieve partial or complete remission in patients with advanced‑stage disease.
• Non‑Hodgkin lymphoma: used in selected indolent or aggressive subtypes to control tumor growth and extend overall survival.

• Chlorambucil exerts its antineoplastic effect by alkylating the N7 position of guanine residues in DNA, creating intra‑ and interstrand cross‑links that impede DNA replication and transcription. As a nitrogen‑mustard derivative, it forms covalent bonds with nucleophilic sites on the DNA backbone, further destabilizing the helix and enhancing cytotoxicity. The cumulative DNA lesions overwhelm repair mechanisms, leading to programmed cell death.

Chlorambucil may cause a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Nausea and vomiting: gastrointestinal upset occurring early in therapy.
• Myelosuppression: decreased white blood cells, red cells, and platelets.
• Fatigue: generalized tiredness affecting daily activities.
• Alopecia: temporary hair loss on scalp and body.
• Diarrhea: loose stools that may require supportive care.

Serious or Rare Side Effects

• Secondary malignancies: increased risk of therapy‑related cancers such as acute leukemia.
• Severe infection: opportunistic infections due to profound neutropenia.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis.
• Hepatotoxicity: elevated liver enzymes and rare liver failure.
• Renal impairment: acute kidney injury in susceptible patients.

Before initiating chlorambucil therapy, clinicians should evaluate patient factors and implement safety measures.

• Baseline blood counts: obtain complete blood count with differential to assess marrow reserve.
• Liver and kidney function: evaluate hepatic enzymes and renal clearance for dose adjustment.
• Infection risk: monitor for signs of infection and consider prophylactic antibiotics in neutropenic patients.
• Pregnancy and lactation: avoid use during pregnancy and breastfeeding unless benefits outweigh risks.
• Drug interactions: review concomitant medications for potential additive myelosuppression.
• Store at ambient temperature: keep tablets in original container, protect from moisture and heat, store below 25 °C.

Chlorambucil can interact with other agents, altering its efficacy or toxicity.

Major Interactions (Avoid)

• Antimetabolites (e.g., methotrexate): combined use markedly increases myelosuppression.
• Live vaccines: immunosuppression may lead to uncontrolled infection.
• CYP2B6 inhibitors: can raise chlorambucil plasma levels, enhancing toxicity.

Moderate Interactions (Monitor Closely)

• Azole antifungals: may increase drug exposure, requiring blood count monitoring.
• Allopurinol: can potentiate hematologic toxicity.
• NSAIDs: may exacerbate gastrointestinal irritation.
• Radiation therapy: concurrent use can amplify bone marrow suppression.