Leukeran (Chlorambucil)

Leukeran (chlorambucil) is used in the management of several lymphoid malignancies, targeting abnormal B‑cell proliferation.

• Chronic lymphocytic leukemia: reduces disease burden by inducing apoptosis of malignant lymphocytes.
• Hodgkin's disease: contributes to remission by damaging proliferating Reed‑Sternberg cells.
• Non‑Hodgkin lymphoma: slows tumor growth through DNA cross‑linking in malignant B‑cells.
• Acute lymphoblastic leukemia: assists in achieving remission by interfering with leukemic cell replication.

• Chlorambucil is an alkylating agent that covalently binds to nucleophilic sites on DNA, forming intra‑ and interstrand cross‑links. These cross‑links impede DNA unwinding, blocking replication and transcription processes. The resulting DNA damage triggers cell‑cycle arrest and apoptosis, preferentially affecting rapidly dividing malignant lymphocytes while sparing most normal cells. The drug is absorbed orally and undergoes hepatic metabolism to active metabolites that retain alkylating activity.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset that may improve over time.
• Vomiting: occasional episodes, often manageable with anti‑emetics.
• Fatigue: generalized tiredness and reduced stamina during therapy.
• Myelosuppression: decreased white blood cells, red cells, and platelets leading to infection risk.
• Alopecia: temporary hair thinning or loss that typically regrows after treatment.
• Diarrhea: loose stools that may require fluid replacement.

Serious or Rare Side Effects

• Secondary malignancies: increased risk of therapy‑related cancers such as acute myeloid leukemia.
• Severe bone marrow failure: pancytopenia requiring transfusion support and possible growth‑factor therapy.
• Pulmonary fibrosis: progressive scarring of lung tissue causing breathlessness.
• Hepatotoxicity: elevated liver enzymes or clinically significant liver injury.
• Severe allergic reactions: rash, angioedema, or anaphylaxis requiring immediate medical attention.

When prescribing chlorambucil, clinicians should observe several precautionary measures to minimize toxicity and ensure safe use.

• Baseline blood counts: obtain complete blood count before initiation and monitor regularly.
• Renal function: assess creatinine clearance, adjust use in severe impairment.
• Pregnancy: contraindicated; avoid use in pregnant women due to fetal toxicity.
• Breastfeeding: discontinue therapy and avoid nursing as drug may be excreted in milk.
• Drug interactions: review concomitant medications that affect bone marrow or hepatic metabolism.
• 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 increasing toxicity.

Major Interactions (Avoid)

• Antimetabolites (e.g., methotrexate): combined myelosuppression may become severe.
• Live vaccines: immunosuppression can reduce vaccine effectiveness and increase infection risk.
• CYP2C9 inhibitors (e.g., fluconazole): may raise chlorambucil plasma levels.

Moderate Interactions (Monitor Closely)

• Warfarin: enhanced anticoagulant effect, monitor INR.
• Allopurinol: possible increase in hematologic toxicity, observe blood counts.
• NSAIDs: may aggravate gastrointestinal irritation.