A 67-year-old female patient with rheumatoid arthritis has been treated with Leukeran (chlorambucil

Fråga: A 67-year-old female patient with rheumatoid arthritis has been treated with Leukeran (chlorambucil) four mg daily for three years with good effect. However, the platelet count of the patient decreased from 300 to 136 and Leukeran was therefore discontinued five months ago. Now the platelet count has increased to 207 and there is a clinical need for Leukeran treatment. Can Leukeran treatment be started again? Is there a risk for irreversible thrombocytopaenia? The patient is also receiving indomethacin 100 mg daily and a low dose of steroids.

Sammanfattning: The main toxic effect of chlorambucil is bone marrow suppression. This depression is usually reversible. A reexposure cannot be regarded as contraindicated. However, other possible treatments (eg cyclophosphamide) should be considered and discussed with a haematologist.

Svar: The main toxic effect of chlorambucil is bone marrow suppression and careful monitoring of the white blood count is necessary. Continued administration in the presence of falling blood counts or a total dosage of 6.5 mg/kg for the course may lead to irreversible bone marrow failure. Under the usual therapeutic conditions the bone marrow depression caused by chlorambucil is readily reversible. At therapeutic dosages chlorambucil depresses lymphocytes and has less effect on neutrophil and platelet counts and on haemoglobin levels (1). Discontinuation of chlorambucil is not necessary at the first sign of a fall in neutrophils (1). The fall may continue for 10 days or more after the last dose (1). Acute overdosage of chlorambucil may lead to irreversible bone marrow failure and there are case reports of acute leukaemia after chlorambucil therapy (1).

In an uncontrolled study of chlorambucil treatment of bullous pemphigoid a mild transient thrombocytopaenia was found in 30 per cent of the patients. The patients that developed thrombocytopaenia were older and had lower pretreatment platelet levels (2).

In another uncontrolled study of chlorambucil treatment in patients with rheumatoid arthritis (3) it was found that haematological complications were more frequent than reported in the literature.

The patient in the present case has had a history of reversible thrombocytopaenia. A reexposure to chlorambucil cannot be regarded as contraindicated provided that there are no alternative treatments for arthritis and that her blood counts are carefully monitored. However, Sendoxan (cyclophosphamide) is another immunosuppressant alkylating substance less prone to cause marrow depression and should be considered as an alternative (4). We recommend, however, that her treatment be discussed with a haematologist before it is begun.