Continuation of clozapine in a patient with lymphoma

To the Editor

Our patient was a 41-year-old male, with a 16-year history of schizophrenia. He was commenced on clozapine in April 2011, following poor clinical efficacy with other antipsychotic agents (flupenthixol, olanzapine, and quetiapine). His mental state improved significantly on a daily dose of clozapine 400 mg.

In December 2011, during an inpatient stay at Nambour General Hospital, he complained of neck swelling. Physical examination revealed bilateral cervical lymph node enlargement with no other lymphadenopathy. The cervical lymph node biopsy conducted in January 2012 revealed follicular lymphoma. A bone marrow biopsy revealed a slow-growing follicular non-Hodgkin lymphoma, low-grade, stage 3A. The haematology team decided against chemotherapy with a plan of frequent follow-up.

Our patient had concerns about the association between clozapine and lymphoma. After an extensive literature search including communication with the pharmaceutical company, we found few cases of lymphomas in patients prescribed clozapine. No direct association between clozapine and lymphoma was found. The outcome of our investigation was discussed with the patient and he decided to continue with clozapine having determined that the benefits outweighed the risks. He also chose to continue clozapine even if he required chemotherapy in the future. His mental state remained stable on clozapine. He is still receiving follow-up with the haematology team without any active intervention at this time.

The case highlights two key learning points: first, current evidence shows no direct association between the onset of lymphoma and taking clozapine; and second, transparency with the communication of information about treatment with a patient may assist in consolidating the therapeutic alliance and fostering patient autonomy.

Clozapine is a recommended option for treatment-resistant schizophrenia. Agranulocytosis is a serious side effect of clozapine, with the highest risk occurring in the initial 6 months (Alhmoud et al., 2007). This patient developed a haematological malignancy independent of clozapine. The neutropenia secondary to the haematological malignancy should not be confused with clozapine-induced agranulocytosis. The patient, family and care-givers obtained a clear understanding of the differences between clozapine-related agranulocytosis and neutropenia-related malignancy when the evidence and case reports were discussed with them (Hundertmark and Campbell, 2001).

If a patient taking clozapine develops a concomitant haematological malignancy, it is imperative for regular cell count monitoring. If a decrease in cell count occurs, it may be a result of haematological malignancy or clozapine. The decision about further continuation of clozapine can be made following the clozapine guidelines and in consultation with haematology and oncology teams.