Chlorambucil

Class: Alkylating agent – Nitrogen mustard derivative.

  • Mechanism of Action:
    • Binds covalently to DNA at the N7 position of guanine.
    • Causes DNA cross-linking and strand breaks → inhibition of DNA replication and transcription → apoptosis.
    • Cell cycle–nonspecific.
  • Clinical Uses:
    • Chronic lymphocytic leukemia (CLL) – historically first-line, now less common with targeted agents (ibrutinib, venetoclax).
    • Indolent non-Hodgkin’s lymphoma.
    • Waldenström’s macroglobulinemia.
    • Sometimes used in pediatric nephrotic syndrome or autoimmune conditions (off-label).
  • Dosing:
    • Oral: 0.1–0.2 mg/kg/day for 3–6 weeks (CLL), or
    • 0.4 mg/kg intermittently every 2–4 weeks.
    • Adjust for bone marrow suppression.
  • Toxicities:
    • Myelosuppression (dose-limiting).
    • Nausea, vomiting, diarrhea (generally mild).
    • Secondary malignancies (acute leukemia, MDS with prolonged use).
    • Rare: pulmonary fibrosis, hepatotoxicity, infertility/amenorrhea.
    • Neurologic toxicity (seizures, tremors) at high doses.
  • Monitoring:
    • CBC (frequent during therapy).
    • Monitor for infections and secondary malignancies.
    • Liver and renal function with prolonged use.

In summary:

Chlorambucil is an oral nitrogen mustard alkylating agent, historically important in CLL and indolent lymphomas. It is well tolerated compared to older agents but carries risks of myelosuppression and secondary malignancies with long-term use.