Leukeran (chlorambucil) is an alkylating antineoplastic agent indicated for the treatment of various hematologic malignancies. As a cornerstone of oral chemotherapy, it offers a targeted approach to managing chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, and certain non-Hodgkin lymphomas. Its mechanism of action involves cross-linking DNA strands, thereby inhibiting cancer cell replication and promoting apoptosis. This product card provides a comprehensive, expert-level overview of Leukeran for healthcare professionals, detailing its pharmacological profile, clinical applications, and essential safety information to support informed therapeutic decisions.

Features

• Active Ingredient: Chlorambucil
• Drug Class: Nitrogen mustard alkylating agent
• Administration: Oral tablet formulation
• Available Strengths: 2 mg tablets
• Pharmacokinetics: Rapid and complete gastrointestinal absorption; extensively metabolized in the liver
• Half-life: Approximately 1.5 hours for chlorambucil; active metabolites have prolonged activity
• Excretion: Primarily renal (minor biliary excretion)

Benefits

• Provides a convenient oral chemotherapy option, facilitating outpatient management and improving patient quality of life
• Demonstrates selective cytotoxicity toward lymphoid cells, making it particularly effective for lymphoproliferative disorders
• Offers flexible dosing regimens that can be titrated based on individual patient response and hematologic parameters
• Shows proven efficacy in inducing and maintaining remission in chronic lymphocytic leukemia
• May be used in combination regimens with other antineoplastic agents for enhanced therapeutic outcomes
• Enables long-term disease control with appropriate monitoring and dose adjustment

Common use

Leukeran is primarily prescribed for the treatment of chronic lymphocytic leukemia (CLL), where it remains a first-line therapeutic option for both untreated and previously treated patients. It is also indicated for Hodgkin lymphoma and certain types of non-Hodgkin lymphoma, particularly follicular lymphoma. In clinical practice, Leukeran may be used as monotherapy or in combination with other chemotherapeutic agents, such as prednisone (in the CLB-P regimen). Off-label uses include treatment of Waldenström’s macroglobulinemia, polycythemia vera, and certain autoimmune conditions requiring immunosuppression, though these applications require careful benefit-risk assessment by treating physicians.

Dosage and direction

Dosage must be individualized based on the specific malignancy, disease stage, hematologic parameters, and patient’s overall condition. For chronic lymphocytic leukemia, initial dosing typically ranges from 0.1 to 0.2 mg/kg body weight daily (approximately 4 to 10 mg daily) for 3 to 6 weeks. Alternative regimens include intermittent dosing of 0.4 mg/kg, increased by 0.1 mg/kg until response or toxicity appears, administered as a single dose every 2 weeks. Tablets should be taken consistently with regard to meals, preferably at the same time each day, and must not be crushed or chewed. Regular blood counts are essential throughout treatment, with dosage adjustments made based on white blood cell and platelet counts. Treatment duration varies from several weeks to continuous maintenance therapy, depending on response and tolerability.

Precautions

Leukeran requires careful hematologic monitoring before and during treatment, with complete blood counts performed weekly initially and at least monthly during maintenance therapy. Patients should be monitored for signs of bone marrow suppression, including fever, sore throat, infections, or unusual bleeding. Secondary malignancies, particularly acute myelogenous leukemia, have been reported with long-term use. Pulmonary fibrosis and seizures have occurred with high-dose therapy. Vaccination with live vaccines should be avoided during treatment. Fertility preservation should be discussed with patients of reproductive potential before initiation of therapy. Hepatic and renal function should be assessed periodically, with dosage adjustment considered in patients with impairment. Patients should be advised to maintain adequate hydration to minimize the risk of hyperuricemia.

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 demonstrated prior resistance to this medication. Use is contraindicated during pregnancy due to the potential for fetal harm, and in nursing mothers unless the potential benefit justifies the risk to the infant. The drug is contraindicated in patients with severe bone marrow suppression or those who have recently received radiation therapy or other chemotherapy causing significant myelosuppression. Patients with known severe hepatic impairment should not receive Leukeran without careful risk-benefit assessment.

Possible side effect

Hematologic: Myelosuppression including leukopenia, thrombocytopenia, anemia, and pancytopenia (common); may be severe and progressive with continued treatment
Gastrointestinal: Nausea, vomiting, diarrhea, oral ulceration (common); hepatotoxicity including jaundice and hepatitis (rare)
Neurologic: Tremors, muscle twitching, confusion, hallucinations, seizures (particularly with high doses)
Dermatologic: Skin rash, urticaria, angioedema; Stevens-Johnson syndrome and toxic epidermal necrolysis (rare)
Pulmonary: Pulmonary fibrosis and interstitial pneumonitis (rare)
Reproductive: Amenorrhea, oligospermia, azoospermia, infertility
Other: Fever, allergic reactions, secondary malignancies (particularly with long-term therapy), tumor lysis syndrome

Drug interaction

Leukeran interacts with several medication classes requiring careful consideration. Concurrent use with other myelosuppressive agents (including other chemotherapy drugs, azathioprine, and immunosuppressants) may potentiate bone marrow toxicity. Live vaccines should be avoided due to diminished immune response and potential for vaccine-induced infection. Drugs that affect hepatic metabolism may alter chlorambucil concentrations; caution is advised with strong CYP inducers or inhibitors. Anticoagulants may require dosage adjustment due to potential effects on platelet function. Concomitant use with uricosuric agents may affect uric acid excretion, potentially increasing the risk of uric acid nephropathy during tumor lysis. Phenytoin may have decreased serum levels when coadministered with Leukeran.

Missed dose

If a dose is missed, patients should take it as soon as remembered unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should never double the dose to make up for a missed one. Healthcare providers should be informed about any missed doses, as this may affect treatment monitoring schedules. For patients on intermittent dosing regimens, the entire treatment plan may need reassessment if multiple doses are missed. Documentation of missed doses is important for accurate assessment of treatment adherence and efficacy.

Overdose

Overdose primarily manifests as irreversible bone marrow suppression, including pancytopenia, which may be fatal. Gastrointestinal toxicity including nausea, vomiting, and mucositis may occur. Neurologic toxicity including agitation, ataxia, and seizures has been reported with massive overdoses. There is no specific antidote for Leukeran overdose. Management consists of immediate discontinuation of the drug and supportive care, including transfusion of blood products and administration of growth factors as needed. Hospitalization is required for close monitoring of hematologic parameters and management of complications. Hemodialysis is not effective due to high protein binding and rapid metabolism. Patients should be monitored for evidence of infection and bleeding for several weeks following overdose.

Storage

Store Leukeran tablets at controlled room temperature (20°C to 25°C or 68°F to 77°F) in the original container with the lid tightly closed. Protect from light and moisture. Keep out of reach of children and pets. Do not store in bathroom cabinets or other areas with high humidity. Unused medication should be disposed of properly according to specific institutional guidelines for cytotoxic drugs. Do not use tablets that show signs of discoloration or physical deterioration. Healthcare facilities should follow appropriate hazardous drug handling procedures during storage and distribution.

Disclaimer

This information is intended for healthcare professionals and should not replace clinical judgment. Treatment decisions must be based on the individual patient’s condition, response to therapy, and comprehensive risk-benefit assessment. Dosage and administration may vary from described protocols based on evolving clinical evidence and institutional guidelines. Prescribers should consult full prescribing information and current clinical literature before initiating therapy. Patients should be fully informed about potential benefits and risks, and appropriate consent should be obtained. The manufacturer’s latest official prescribing information takes precedence over any content provided here.

Reviews

Clinical studies have established Leukeran as an effective treatment for chronic lymphocytic leukemia, with response rates ranging from 40% to 70% in treatment-naïve patients. The CLL4 trial demonstrated similar overall survival between chlorambucil monotherapy and fludarabine-based regimens in older patients with comorbidities, though with different toxicity profiles. Long-term follow-up data show durable responses in a subset of patients, particularly those with mutated IGHV status. In lymphoma, response rates vary by histology, with higher responses in low-grade compared to aggressive subtypes. Real-world evidence supports its continued role in elderly patients and those with significant comorbidities who may not tolerate more aggressive regimens. Ongoing research continues to refine its place in combination therapies and maintenance regimens.