Leukeran (chlorambucil) is an alkylating antineoplastic agent indicated for the treatment of various hematologic malignancies. As a nitrogen mustard derivative, it exerts its cytotoxic effects by cross-linking DNA strands, thereby inhibiting replication and transcription in rapidly dividing cells. This oral chemotherapy medication is a cornerstone in the management of certain chronic lymphoproliferative disorders, offering a well-established efficacy profile with a manageable side effect spectrum when administered under appropriate medical supervision. Its oral formulation provides significant advantages in treatment convenience and outpatient management.

Features

• Active ingredient: Chlorambucil
• Drug class: Alkylating antineoplastic agent (nitrogen mustard derivative)
• Administration: Oral tablet formulation
• Available strengths: 2 mg tablets
• Mechanism: Forms covalent bonds with DNA nucleophilic sites, causing cross-linking and inhibition of DNA replication
• Metabolism: Hepatic via oxidation to phenylacetic acid mustard
• Excretion: Primarily renal (60% within 24 hours)
• Half-life: Approximately 1.5 hours for chlorambucil; active metabolites have longer half-lives

Benefits

• Provides targeted cytotoxic activity against malignant lymphocytes with selective toxicity
• Enables convenient oral administration, facilitating outpatient treatment and improving quality of life
• Demonstrates established efficacy in indolent lymphoproliferative disorders with predictable response patterns
• Offers flexible dosing regimens that can be titrated based on hematologic parameters and clinical response
• Maintains a generally manageable safety profile when properly monitored by oncology specialists
• Serves as a foundation for combination chemotherapy regimens in certain hematologic malignancies

Common use

Leukeran is primarily indicated for the palliative treatment of chronic lymphocytic leukemia (CLL) and malignant lymphomas, including Hodgkin’s lymphoma and non-Hodgkin’s lymphomas. It is particularly effective in the management of advanced-stage CLL where it demonstrates significant activity against malignant B-cells. The medication may also be used off-label for certain autoimmune conditions requiring potent immunosuppression, such as refractory nephrotic syndrome or autoimmune hemolytic anemia, though these applications require careful risk-benefit assessment. In oncology practice, leukeran is often employed when a less aggressive chemotherapy approach is warranted, especially in elderly patients or those with significant comorbidities who may not tolerate more intensive regimens.

Dosage and direction

Dosage must be individualized based on the specific malignancy, disease stage, hematologic parameters, and patient tolerance. For chronic lymphocytic leukemia, the initial daily dose typically ranges from 0.1 to 0.2 mg/kg (approximately 4 to 10 mg daily) for 3 to 6 weeks. Alternative intermittent dosing schedules may utilize 0.4 mg/kg administered as a single dose every 2 weeks, with incremental increases of 0.1 mg/kg until response or toxicity occurs. Tablets should be taken whole with water, preferably at the same time each day, and may be administered with food to minimize gastrointestinal discomfort. Complete blood counts should be monitored weekly during initiation and regularly throughout treatment, with dosage adjustments made based on hematologic parameters. Treatment duration varies from several weeks to continuous maintenance therapy, depending on clinical response and tolerability.

Precautions

Leukeran requires careful hematologic monitoring due to its myelosuppressive effects. Complete blood counts with differential should be obtained weekly during initial treatment and at regular intervals thereafter. Secondary malignancies, particularly acute myelogenous leukemia, have been reported with long-term use. The drug is mutagenic and teratogenic, requiring appropriate contraceptive measures in patients of reproductive potential. Hepatic and renal function should be assessed periodically, as impairment may alter drug metabolism and excretion. Patients should be monitored for signs of infection, bleeding, or anemia throughout treatment and for several months after discontinuation. Vaccination with live vaccines should be avoided during treatment due to the risk of disseminated infection.

Contraindications

Leukeran is contraindicated in patients with demonstrated hypersensitivity to chlorambucil or any component of the formulation. It should not be administered to patients who have previously demonstrated resistance to the drug. The medication is contraindicated during pregnancy (Category D) due to proven fetal risk, and adequate contraception must be used during treatment and for several months afterward. Use is contraindicated in patients with severe bone marrow suppression (absolute neutrophil count <1500/mm³ or platelet count <100,000/mm³) unless the potential benefit justifies the risk. The drug should not be administered concurrently with live vaccines. Patients with severe hepatic impairment require careful consideration due to altered metabolism.

Possible side effect

• Hematologic: Myelosuppression including leukopenia, thrombocytopenia, anemia, and pancytopenia (dose-limiting)
• Gastrointestinal: Nausea, vomiting, diarrhea, oral ulceration, abdominal discomfort
• Dermatologic: Skin rash, urticaria, angioedema, rare cases of Stevens-Johnson syndrome
• Neurologic: Seizures (particularly at high doses), peripheral neuropathy, confusion
• Pulmonary: Pulmonary fibrosis (rare but serious), interstitial pneumonitis
• Reproductive: Amenorrhea, oligospermia, azoospermia, infertility (may be permanent)
• Hepatic: Hepatotoxicity, jaundice, elevated transaminases
• Other: Fever, allergic reactions, secondary malignancies, tumor lysis syndrome

Drug interaction

Leukeran exhibits significant interactions with other myelosuppressive agents, including other chemotherapy drugs, increasing the risk of severe bone marrow suppression. Concurrent use with live vaccines may diminish vaccine efficacy and increase risk of vaccine-related infections. Drugs that affect hepatic cytochrome P450 enzymes may alter chlorambucil metabolism. Anticoagulants may have enhanced effects due to potential thrombocytopenia. Phenobarbital may increase chlorambucil metabolism, potentially reducing efficacy. Succinylcholine may have prolonged neuromuscular blockade due to decreased pseudocholinesterase activity. Nephrotoxic agents may reduce excretion and increase toxicity.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In such cases, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should never double the dose to make up for a missed administration. If multiple doses are missed or vomiting occurs shortly after administration, medical advice should be sought for guidance on dose adjustment or rescheduling. Treatment interruptions may require re-evaluation of the dosing regimen by the treating physician.

Overdose

Overdose manifests primarily as irreversible bone marrow suppression, including pancytopenia, with nadir occurring 1-3 weeks after ingestion. Gastrointestinal toxicity including nausea, vomiting, and diarrhea may be prominent. At very high doses, neurotoxicity including seizures, muscle twitching, and confusion may occur. There is no specific antidote for chlorambucil overdose. Management involves immediate discontinuation of the drug, supportive care including transfusion support for hematologic complications, and aggressive management of infections. Hemodialysis is not effective due to high protein binding. Hospitalization with hematologic monitoring for several weeks is typically required.

Storage

Leukeran tablets should be stored at controlled room temperature (20-25°C or 68-77°F) in their original container. The medication must be protected from light and moisture. Tablets should not be removed from their blister packaging until immediately before administration. Keep out of reach of children and pets. Do not use tablets that show signs of discoloration or deterioration. Proper disposal of unused medication is essential, preferably through drug take-back programs to prevent environmental contamination and accidental exposure.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Leukeran is a prescription medication that should only be used under the supervision of a qualified healthcare professional experienced in cancer chemotherapy. Treatment decisions must be based on individual patient factors, and the benefits and risks should be carefully evaluated. The information presented here may not include all possible uses, directions, precautions, or interactions. Always consult with a healthcare provider for personalized medical advice and before making any changes to treatment regimens.

Reviews

Clinical studies have demonstrated Leukeran’s efficacy in chronic lymphocytic leukemia, with response rates ranging from 50-70% in treatment-naïve patients. Many hematologists note its particular value in elderly patients and those with comorbidities who may not tolerate more aggressive regimens. The oral formulation is frequently cited as significantly improving quality of life compared to intravenous alternatives. However, specialists emphasize the importance of careful monitoring due to the delayed myelosuppression that characterizes this agent. Long-term follow-up data confirms the risk of secondary malignancies, particularly with prolonged use, necessitating careful risk-benefit assessment for each individual patient. Many oncologists consider Leukeran an important tool in the hematologist’s armamentarium, particularly for palliative management of indolent lymphoproliferative disorders.