In a proportion of patients usually after about 2 years of treatment, the blood leukocyte count is reduced to the normal range, enlarged spleen and lymph nodes become impalpable and the proportion of lymphocytes in the bone marrow is reduced to less than 20 per cent.

Patients with evidence of bone marrow failure should first be treated with prednisolone and evidence of marrow regeneration should be obtained before commencing treatment with Leukeran.

Intermittent high dose therapy has been compared with daily Leukeran but no significant difference in therapeutic response or frequency of side effects was observed between the two treatment groups.

Waldenstrom's macroglobulinaema:-

Leukeran is the treatment of choice in this indication.

Starting doses of 6-12 mg daily until leucopenia occurs are recommended followed by 2-8 mg daily indefinitely.

Children:-

Leukeran may be used in the management of Hodgkin's disease and non- Hodgkin's lymphomas in children. The dosage regimens are similar to those used in adults.

Use in the elderly:-

No specific studies have been carried out in the elderly, however, it may be advisable to monitor renal or hepatic function and if there is serious impairment then caution should be exercised.
 

4.3 Contraindications

 Use in the management of patients with non-malignant disease.

Hypersensitivity to chlorambucil or to any of the excipients.

4.4 Special warnings and precautions for use

 LEUKERAN IS AN ACTIVE CYTOTOXIC AGENT AND SHOULD ONLY BE ADMINISTERED UNDER THE DIRECTION OF A SPECIALIST ONCOLOGY SERVICE HAVING THE FACILITIES FOR REGULAR MONITORING OF CLINICAL BIOCHEMICAL AND HAEMATOLOGICAL EFFECTS DURING AND AFTER ADMINISTRATION.

Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised individuals. Therefore, immunisations with live organism vaccines are not recommended.

Safe handling of Leukeran Tablets:- See 6.6 Instructions for Use/Handling.

Monitoring:-

Since Leukeran is capable of producing irreversible bone marrow suppression, blood counts should be closely monitored in patients under treatment. Total dosage in the region of 6.5mg/kg bodyweight is associated with the risk of irreversible bone marrow damage.

At therapeutic dosage Leukeran depresses lymphocytes and has less although progressive effect on neutrophil and platelet counts and on haemoglobin levels.

Discontinuation of Leukeran is not necessary at the first sign of a fall in neutrophils but it must be remembered that the fall may continue for 10 days or more after the last dose.

Leukeran should not be given to patients who have recently undergone radiotherapy or received other cytotoxic agents.

Chlorambucil should only be used with caution in patients with depressed bone narrow function or lymphocytic infiltration of same.

When lymphocytic infiltration of the bone marrow is present or the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg bodyweight.

Children with nephrotic syndrome, patients prescribed as high pulse dosing regimens and patients with a history of seizure disorder, should be closely monitored following administration of Leukeran, as they may have an increased risk of seizu