Leukeran (Chlorambucil)

Leukeran (chlorambucil) is used in the management of lymphoid malignancies, where it interferes with DNA replication in malignant cells.

• Chronic lymphocytic leukemia (CLL): induces remission or disease control by targeting proliferating lymphocytes.
• Hodgkin's lymphoma: contributes to tumor reduction and prolongs progression‑free survival when used in combination regimens.
• Non‑Hodgkin lymphoma: provides cytoreduction and can achieve partial or complete responses in eligible patients.
• Other lymphoid malignancies: offers therapeutic benefit in selected cases of mantle‑cell, follicular, or other rare lymphoid cancers.

• Chlorambucil is an alkylating agent that forms covalent bonds with the N‑7 position of guanine bases in DNA, creating intra‑ and interstrand cross‑links. These cross‑links impede DNA unwinding and replication, leading to cell cycle arrest and apoptosis of rapidly dividing malignant lymphocytes. The drug’s non‑selective alkylation also affects normal proliferating cells, which underlies its therapeutic activity and toxicity profile. Because it does not require metabolic activation, chlorambucil exerts its effect after oral absorption and systemic distribution.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Fatigue: generalized tiredness affecting daily activities.
• Myelosuppression: decreased white blood cells, red cells, or platelets.
• Alopecia: temporary hair thinning or loss.

Serious or Rare Side Effects

• Secondary malignancies: increased risk of therapy‑related leukemia or solid tumors.
• Severe infection: due to profound neutropenia leading to febrile episodes.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis in rare cases.

When prescribing chlorambucil, clinicians should consider several precautionary measures to minimize risk.

• Baseline blood counts: obtain complete blood count before initiation and monitor regularly.
• Renal function: assess creatinine clearance as impaired function may increase exposure.
• Hepatic function: evaluate liver enzymes; dose adjustment may be needed in severe disease.
• Pregnancy: avoid use during pregnancy due to potential teratogenicity; discuss contraception.
• Concomitant immunosuppressants: use caution with other myelosuppressive agents to prevent excessive bone‑marrow suppression.
• Store at ambient temperature: keep tablets below 25 °C in the original container, protect from moisture and light.

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

Major Interactions (Avoid)

• Live vaccines: increased risk of infection; avoid administration during therapy.
• Strong CYP450 inducers: agents such as rifampin may reduce chlorambucil plasma levels.

Moderate Interactions (Monitor Closely)

• Anticoagulants: enhanced bleeding risk; monitor INR or PT.
• Other alkylating agents: additive myelosuppression; adjust dosing.
• Allopurinol: may increase chlorambucil toxicity; observe blood counts.