621389
research-article2015
ANP0010.1177/0004867415621389ANZJP CorrespondenceANZJP Correspondence
Letter
Letter
Lymphoma developing
during clozapine therapy
Michele Meltzer
Ryde Community Mental Health Service,
Northern Sydney LHD, Eastwood, NSW,
Australia
Corresponding author:
Michele Meltzer, Ryde Community Mental
Health Service, Northern Sydney LHD, 39-41
Fourth Av, Eastwood, NSW 2122, Australia.
Email: Michele.meltzer@health.nsw.gov.au
DOI: 10.1177/0004867415621389
To the Editor
Ryde Community Mental Health Service
is a busy centre, catering for a large
number of people with a chronic mental
illness. At any one time, about 170
patients with a diagnosis of treatment
resistant schizophrenia are being
treated with the antipsychotic clozap-
ine. In the last 11 years, at Ryde, 5 out of
a total of 221 patients taking clozapine
have developed lymphoma. There are
also reports of cases at other centres.
The lymphomas have been of varying
types: two Burkitt’s lymphomas, two
non-Hodgkin’s lymphomas (NHLs), and
one follicular NHL (Table 1). All five
patients were treated for their lym-
phomas at local public hospitals and
were able to continue taking their clo-
zapine throughout their treatment, in
consultation with the clozapine
haematologist.
The two members of the group
with Burkitt’s lymphoma died. The
remaining three NHLs continue to
receive treatment.
According to the Cancer Institute of
New South Wales (NSW), the lifetime
incidence of NHL up to age 85 is 1/42,
which is common. However, the three
NHLs occurred between ages 51 and
Downloaded from anp.sagepub.com at UNIV OF PITTSBURGH on February 6, 2016
Table 1.  Patient ages at the start of clozapine and onset lymphoma.
Patient Started clozapine
A 35
B 32
C 47
D 42
E 39
NHL: non-Hodgkin’s lymphoma.
59. The incidence of Burkitt’s lymphoma
is about 1% of all NHL, that is, 1/4200.
After contacting the Adverse Drug
Reactions Advisory Committee
(ADRAC) in Canberra, their Signals
Investigation Unit did a search on this
topic. They reported that crude
reporting rates for lymphoma associ-
ated with clozapine use across
Australia are in keeping with esti-
mated background population inci-
dence – except for the Ryde cluster.
A literature search shows a num-
ber of individual case reports, mainly
relating to continuing clozapine
through chemotherapy (Ali et  al.,
2014; Munshi et al., 2013). One 2010
report from Denmark questions a link
between clozapine and acute myelo-
cytic leukaemia, based on a register
search showing 4/3779 cases and con-
cluding an eight-fold increased risk.
(Nielsen and Boysen, 2010)
The question is whether the Ryde
cluster is simply a coincidence, or
whether there might be a trend, but
general under-reporting by doctors
who do not see a connection. In pub-
lic hospitals and community centres,
many clozapine patients are treated
by registrars on 6-month rotations,
leading to non-continuity of the
observer.
Australian & New Zealand Journal of Psychiatry
1­–1
© The Royal Australian and
New Zealand College of Psychiatrists 2015
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Onset lymphoma Type
40 Burkitt’s – deceased
39 Burkitt’s – deceased
58 NHL
53 NHL
51 Follicular NHL
The purpose of this letter is to
raise awareness and the index of sus-
picion, and report to ADRAC any
cases of patients developing lymphoma
while being treated with clozapine.
Acknowledgement
I am grateful for the support and assis-
tance of Dr Luke Coyle, consultant hae-
matologist at Royal North Shore Hospital
in the Northern Sydney LHD.
Declaration of interest
The author(s) declared no potential con-
flicts of interest with respect to the
research, authorship, and/or publication
of this article.
Funding
The author(s) received no financial sup-
port for the research, authorship and/or
publication of this article.
References
Ali MS, Lehmann-Waldau F and Taikato RM (2014)
Continuation of clozapine in a patient with
lymphoma. Australian and New Zealand Journal
of Psychiatry 48: 1066–1067.
Munshi T, Mazhar M and Hassan T (2013)
Clozapine reinitiation following a ‘red result’
secondary to chemotherapy. Neuropsychiatric
Disease and Treatment 9: 1267–1271.
Nielsen J and Boysen A (2010) Clozapine treat-
ment associated with increased risk of acute
myeloid leukemia (AML). Schizophrenia
Research 123: 270–272.
Australian & New Zealand Journal of Psychiatry