state of the art review
How I manage priapism in chronic myeloid leukaemia
patients
Ryan Rodgers,1 Zak Latif2 and Mhairi Copland1,3
1
Bone Marrow Transplant Unit, Beatson West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, 2Department of
Urology, Royal Alexandra Hospital, Paisley, and 3Paul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of
Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
Summary
Priapism is a rare presenting feature of chronic myeloid leu-
kaemia (CML). It is a urological emergency requiring urgent
treatment to prevent long-term complications, in particular
erectile dysfunction. In males with CML, ischaemic priapism
is believed to result from hyperleucocytosis and associated
leucostasis or hyperviscosity, and is seen in patients present-
ing with a high white cell count. Increasingly, a combined
modality approach is being used to treat CML patients pre-
senting with priapism. This includes systemic therapy with
chemotherapy (hydroxycarbamide or tyrosine kinase inhibi-
tors) and therapeutic leukapheresis to reduce the white cell
count as well as local intracavernous therapy. This review will
examine the literature and discuss the presenting features,
investigations and management of priapism in CML.
Keywords: chronic myeloid leukaemia, erectile dysfunction.,
intracavernous therapy, leukapheresis, priapism.
Introduction
Chronic myeloid leukaemia (CML) develops when a single,
multipotent haemopoietic stem cell acquires the Philadelphia
(Ph) chromosome which is an abnormal, shortened chromo-
some 22 that results from a reciprocal translocation between
the long arms of chromosomes nine and 22 and is designated
t(9;22)(q34;q11) (Rowley, 1973). In the 1980’s, it was shown
that this translocation resulted in the ABL1 proto-oncogene,
normally on chromosome 9, becoming juxtaposed with the
breakpoint cluster region (BCR) on chromosome 22 (Bartram
et al, 1983; Groffen et al, 1984), resulting in production of
the unique fusion gene product BCR-ABL1, a 210 kD onco-
protein, often referred to as p210BCR-ABL1, which is a consti-
Correspondence: Mhairi Copland, Paul O’Gorman Leukaemia
Research Centre, Gartnavel General Hospital, 1053 Great Western
Road, Glasgow G12 0YN, UK.
E-mail: Mhairi.Copland@glasgow.ac.uk
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British Journal of Haematology, 2012, 158, 155–164
tutively active tyrosine kinase (Lugo et al, 1990). The Ph
chromosome appears in the myeloid, erythroid, megakaryo-
cytic and lymphoid cells of CML patients.
Chronic myeloid leukaemia is a myeloproliferative disor-
der and accounts for 15–20% of all leukaemias in adults
(Faderl et al, 1999). The incidence of CML is constant
worldwide, at 1·0–1·5 per 100 000 of the population. The
median age of onset is 40–60 years; however, it may occur in
children and the very old. There is a slight male predomi-
nance (1·4:1). CML has three stages: chronic phase (CP);
accelerated phase (AP); and blast crisis (BC). It is usually
diagnosed in CP, which is characterized by a leucocytosis
due to increased granulopoiesis with hepatosplenomegaly as
a result of leukaemic infiltration.
The peripheral blood and bone marrow in CP CML usu-
ally have a distinct morphological appearance. There is a
leucocytosis, usually >50 9 109/l, but occasionally >500 9
109/l with a complete spectrum of myeloid cells present in
the peripheral blood. The bone marrow is usually very hy-
percellular with marked granulocytic hyperplasia and the
myeloid:erythoid ratio often exceeds 10:1. In addition to the
characteristic blood and bone marrow appearances in CML,
patients may present with abdominal pain due to splenomeg-
aly (present in >50% of patients at diagnosis) or features of
hyperleucocytosis with leucostasis/hyperviscosity (Rowe &
Lichtman, 1984; Adams et al, 2009). Hyperleucocytosis is
defined as an extreme elevation of the white cell count to
>100 9 109/l. Leucostasis as a result of hyperleucocytosis is
present in ~12% of adults presenting with CML and
approaching 60% of children diagnosed with CML (Adams
et al, 2009). The most recognized features of hyperleucocyto-
sis in CML are constitutional (malaise and fever), cardiore-
spiratory (e.g. breathlessness, chest pain, pulmonary
leucostasis), neurological (e.g. headache, confusion, cranial
nerve palsies) or vascular (e.g. retinal haemorrhage, myocar-
dial ischaemia, priapism). It is believed that priapism in
CML and other haematological malignancies results from hy-
perviscosity due to hyperleucocytosis and venous obstruction
as a result of thrombi and microthrombi (Mulhall & Honig,
1996). More recent studies also suggest that increased pro-
duction of cytokines and adhesion molecules by leukaemia
First published online 10 May 2012
doi:10.1111/j.1365-2141.2012.09151.x
Review
cells results in endothelial cell activation and leads to
increased sequestration of cells in the microvasculature
(Stucki et al, 2001).
The condition priapism was named after the Greek god
Priapus, thought to be the son of Zeus. It is believed that a
jealous Hera or Aphrodite cast a spell over his mother while
pregnant (either Aphrodite or Chloe) causing Priapus to be
born with the affliction bearing his name and resulting in
him being disowned by his mother. Priapism is a urological
emergency, which must be treated early to prevent erectile
dysfunction, and is defined as a persistent penile erection
that continues hours (4 h) beyond, or is unrelated to, sexual
stimulation (Montague et al, 2003). Priapism of the clitoris
in females has been reported but is extremely rare. Priapsim
is a rare condition on its own with an incidence of 1·5 cases
per 100 000 person-years (Eland et al, 2001). Haematological
conditions are the cause of 20% of cases of priapism in men.
Depending on the case series, priapism is seen in between 1
and 5% of male patients with all types of leukaemia
(Schreibman et al, 1974; Becker et al, 1985; Morano et al,
2000; Allue Lopez et al, 2004; Vilke et al, 2004). Of this small
overall percentage, CML accounts for 50% of all leukaemic
priapisms. However, as a presenting feature of CML, pria-
pism is rare in male patients, occurring in 1–2%. There is a
bimodal age distribution in males of 5–10 and 20–50 years
old, but it has been described in all age groups (Cherian
et al, 2006). Although it is a rare problem to present to med-
ical services, haematological conditions are the leading cause
of ischaemic priapism (Table I).
Penile anatomy and normal physiology of penile erection
The human male penis is divided into two areas, the body
and the root. The root begins below the bulbourethral
glands with the corpus spongiosum extending to the glans
penis. The urethra runs through the centre of the corpus
spongiosum. The corpora cavernosa are a pair of cyclindri-
cal bodies that occupy the sides and upper portion above
the corpus spongiosum, terminating before the glans penis.
The corpora cavernosa are made of empty space divided by
partitions of muscle, collagen and elastic fibre. Figure 1
shows the cross-sectional anatomy of the flaccid and erect
penis.
The cavernous smooth musculature and smooth muscles
of the arterial and arteriolar walls play a predominant role in
the erectile process. When the penis is flaccid, the smooth
muscles are contracted allowing a small amount of arterial
blood for nutrition. The blood partial pressure is approxi-
mately 35 mmHg (Sattar et al, 1995). Sexual stimulation
causes the release of neurotransmitters from the cavernous
nerve terminals. This leads to smooth muscle relaxation and
(i) dilatation of the arterioles and arteries by increased blood
flow in both the diastolic and the systolic phases; (ii) trap-
ping of the incoming blood by the expanding sinusoids; (iii)
compression of the subtunical venular plexuses between the
156
Table I. Causes of priapism.
Haematological causes of priapism
Hyperviscosity syndromes
CML
Polycythaemia vera
Multiple myeloma
Amyloidosis
Sickle cell disease
Hypercoagulable states
Protein C and S deficiencies, antiphospholipid syndrome
Cauda equine syndrome secondary to spinal metastasis
Brainstem metastasis
Non-haematological causes of priapism
Idiopathic
Drugs
Sildenafil
Injectable medication for erectile dysfunction – papaverine,
phentolamine, and prostaglandin E1
Antipsychotics – trazadone, olanzapine, quetiapine and
chlorpromazine
Anticoagulants – heparin and warfarin
Vancomycin
Omeprazole
Hydralazine
Illicit drugs – cocaine, ecstacy and marijuana
Alcohol abuse
Neoplasms – bladder, testis and penis
Trauma
Neurological – spinal cord injury, cauda equina compression
Infection – malaria and Mycoplasma pneumoniae
tunica albuginea and the peripheral sinusoids, reducing the
venous outflow; (iv) stretching of the tunica to its capacity
occluding the emissary veins between the inner circular and
the outer longitudinal layers and decreasing the venous out-
flow to a minimum; (v) an increase in PO2 (to about
90 mmHg) and intracavernous pressure (around
100 mmHg), which raises the penis from the dependent
position to the erect state (the full-erection phase); and (vi)
a further pressure increase (to several hundred millimetres of
mercury) with contraction of the ischiocavernosus muscles
(rigid-erection phase) (Dean & Lue, 2005).
There are three phases of detumescence (Bosch et al,
1991). Firstly, there is smooth muscle contraction against a
closed venous system, leading to a transient intracorporeal
pressure increase. Next, there is a slow reopening of the
venous channels with resumption of arterial flow, resulting
in a slow pressure decrease. Finally, there is a fast pressure
decrease with fully restored venous outflow capacity.
Haemodynamics in the corpus spongiosum and glans
penis are different to those in the corpora cavernosa. In an
erection the arterial flow is only one-third to one half of that
in the corpora cavernosa due to the thin tunical covering
ensuring minimal venous occlusion. The spongiosum
and glans act as a large arteriovenous shunt during full-erec-
tion. Further engorgement and increased pressure in the
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British Journal of Haematology, 2012, 158, 155–164

Flaccid
Deep
dorsal vein
Dorsal artery
Tunica
albuginea
Corpus
cavernosum
Urethra
Corpus
spongiosum
Fig 1. Cross-sectional diagram of the anatomy of the penis in flaccid (left) and erect (right) states.
spongiosum and glans results from the ischiocavernosus and
bulbocavernosus muscles compressing the spongiosum and
penile veins.
The penis has both autonomic and somatic innervation.
The sympathetic and parasympathetic nerves merge to form
the cavernous nerves. These enter the corpora cavernosa and
corpus spongiosum controlling neuromuscular events of
erection. The somatic nerves control contraction of the
bulbocavernosus and ischiocavernosus muscles and penile
sensation.
Classification of priapism
Priapism is caused by the persistent engorgement of the cor-
pora cavernosa due to disturbance of vascular mechanisms
that control penile rigidity. Clinically and pathologically,
there are two main types: ischaemic (low flow) and non-is-
chaemic (high flow) priapism. This separation is also
required for appropriate management.
Ischaemic (low flow) priapism. Ischaemic (low flow) pria-
pism is a painful persistent erection that has reduced intra-
cavernous blood flow. This is a type of compartment
syndrome, with reduced venous outflow leading to stasis, aci-
dosis and hypoxia. Ischaemic priapism is the most common
subtype and is an emergency. If untreated within 24–48 h,
this can result in irreversible damage and fibrosis, leading to
problems with erectile dysfunction or future episodes of per-
sistent and prolonged priapism (stuttering priapism). Reports
suggest that priapism lasting 5–10 d leads to impotence in
35–90% of men (Becker et al, 1985; Morano et al, 2000;
Pryor et al, 2004; Vilke et al, 2004). Causes of ischaemic pri-
apism include idiopathic, haematological disorders (Fowler
et al, 1991; Hamre et al, 1991), tumour infiltrate (Powell
et al, 1985), or drug-induced (Saenz de Tejada et al, 1991;
Lomas & Jarow, 1992).
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British Journal of Haematology, 2012, 158, 155–164
Review
Erect
Cavernosal Widened
artery cavernosal
artery
Dilated
corpus
cavernosum
Open veins
Closed veins
Non-ischaemic (high flow) priapism. This is neither a painful
nor fully rigid, persistent erection and is due to unregulated
cavernous arterial flow. This results in increased arterial flow
that overwhelms venous outflow. Therefore the blood
remains oxygenated on aspiration. This makes irreversible
damage or fibrosis rare. Non-ischaemic priapism is most
commonly due to trauma to the penis or perineum (Bastuba
et al, 1994; Ji et al, 1994; Ilkay & Levine, 1995). This causes
injury to the internal pudendal artery leading to a fistula
between the cavernosal artery and corpus cavernosum. This
is not a medical emergency and can be treated electively.
Stuttering priapism. Stuttering priapism is a recurrent form
of ischaemic priapism where unwanted painful erections
occur with periods of detumescence. Stuttering priapism is
more common in patients with haematological problems. It
is particularly seen in sickle cell disease, occurring in up to
28% of these patients (Emond et al, 1980). In sickle cell dis-
ease, these attacks are commonly at night and don’t lead to
permanent erectile dysfunction. Stuttering priapism is rare in
CML patients due to the leucoreduction that rapidly occurs
with systemic treatment of CML.
Pathophysiology
Priapism was firstly described by Hinman (1914) as ‘throm-
bosis of the veins of the corpora’. This hypothesis was fur-
thered by his son, who described the finding of dark, viscous
blood in the corpora cavernosa of the priapic penis, suggest-
ing vascular stasis and reduced venous outflow (Hinman,
1960).
New theories are evolving regarding the underlying patho-
physiology of priapism. This includes the possible dysregula-
tion of nitric oxide (NO) signalling in the penile vasculature.
This occurs because changes in oxygen tension alter the
activity of NO synthase, leading to reduced NO production
157
Review
by the corpora cavernosa in hypoxia (Keoghane et al, 2002).
In ischaemic priapism, the reduced production of prostaglan-
din I2 and NO, which occurs in hypoxia, leads to platelet
aggregation and increased white cell adhesion, resulting in
thrombus formation and tissue damage.
Haematological conditions that alter normal vascular
homeostasis feature abnormal or depleted NO activity
(Champion et al, 2005; Bivalacqua et al, 2007). This dysregu-
lation alters the smooth muscle tone that controls penile
tumescence. When smooth muscle tone control is poor,
responses to normal erectile stimuli are increased, leading to
priapism. The hypoxia, acidosis and glucopenia seen in hae-
matological disorders also alter smooth muscle tone (Yuan
et al, 2008). Other molecular mechanisms that may lead to
priapism in haematological patients include the role of aden-
osine and opiorphins (Mi et al, 2008; Kanika et al, 2009).
Adenosine is a vasodilator and facilitator of erections. It
works via adenylyl cyclase and cyclic adenosine monophos-
phate (cAMP). Figure 2 shows differences in the molecular
pathways involved in a normal erection and priapism. Aden-
osine deaminase deficiency leads to excess levels of adenosine
causing priapism (Mi et al, 2008). Studies also suggest
opiorhins may induce priapism via ornithine decarboxylase
(Kanika et al, 2009).
Ischaemic (low flow) priapism results from the sludging
of blood within the corpora, which are usually fully rigid.
This results in tissue ischaemia and smooth muscle hypoxia
leading to pain (Keoghane et al, 2002). Ischaemic priapism
that lasts more than 4 h and is untreated may resolve spon-
taneously. However, the risk of erectile dysfunction increases
(A) Physiology of normal erection
NANC NO
Guanylate cyclase
Flaccid penis GTP
5´GMP
(B) Pathophysiology of priapism
NANC NO
Guanylate cyclase
Flaccid penis GTP
5´GMP
Fig 2. Signalling pathways in a normal erection and in priapism. (A) Physiology of normal erection and (B) pathophysiology of priapism. NANC,
non-adrenergic non-cholinergic nervous system; NO, nitric oxide; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophosphase; PDE5,
phosphodiesterase 5; 5′GMP, guanosine 5′ monophosphate.
158
with each episode. Ninety per cent of men with ischaemic
priapism lasting more than 24 h developed erectile dysfunc-
tion (Pryor et al, 2004). After 12 h of priapism, trabecular
oedema and thickening is seen (Spycher & Hauri, 1986). At
24 h, platelets adhere to the basement membrane of the sinu-
soidal endothelium and after 48 h, there is cavernosal
smooth muscle necrosis with thrombi in the sinusoidal
spaces and proliferation of fibroblasts. Ischaemia lasting
24–48 h, causes endothelial and trabecular destruction, with
subsequent irreversible fibrosis and calcification, leading to
erectile dysfunction.
The most common haematological condition associated
with priapism is homozygous sickle cell disease. In Jamaica,
sickle cell disease affects one in 300 births. In this popula-
tion, priapism has a prevalence of 42% (Emond et al, 1980;
Serjeant, 1981). A male patient with sickle cell disease has a
89% chance of having a priapism episode by the age of
20 years (Mantadakis et al, 1999). Priapism is rarely seen in
sickle cell trait. Non-ischaemic priapism has also been associ-
ated with sickle cell disease (Ramos et al, 1995). Stuttering
priapism is also commonly seen in sickle cell disease.
In CML patients, the hyperleucocytosis is considered to be
the cause of priapism. The primary mechanism is the aggre-
gation of leukaemic cells in the corpora cavernosa and the
dorsal veins of the penis (Jameel & Mehmood, 2009). A con-
tributing factor is the venous congestion of the corpora cav-
ernosa due to mechanical pressure on the abdominal veins
by the enlarged spleen. A further proposed hypothesis is
infiltration of the sacral nerves or the central nervous system
with leukaemic cells. Although this is discussed as a possible
cGMP Erect penis
Smooth muscle
relaxation of the
cavernosal veins and
emissary veins
PDE5
cGMP PRIAPISM
PDE5
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British Journal of Haematology, 2012, 158, 155–164

mechanism for the development of priapism in the literature,
there is no evidence to support this in leukaemia.
While priapism is most associated with CML, there are
occasional case reports of priapism with other forms of leu-
kaemia including acute myeloid leukaemia (AML), acute
lymphoblastic leukaemia and chronic lymphocytic leukaemia
(Steinhardt & Steinhardt, 1981; Mentzel et al, 2004; Casta-
gnetti et al, 2008; Gogia et al, 2012). It is proposed that the
mechanism of priapism development – hyperleucocytosis
leading to aggregation of leukaemic cells in the corpora cav-
ernosa – is the same in all types of leukaemia, although there
is a single case report for direct leukaemic infiltration of the
penile shaft in AML leading to priapism (Chaux et al, 2011).
Priapism is more frequently seen as a complication in paedi-
atric leukaemia.
Diagnosis
The primary concern in patients presenting with priapism is
to assess whether it is ischaemic or non-ischaemic in nature.
This will determine the management pathway required. As
with all areas of medicine it follows the history, examination
and investigation pathway.
History. The history will help assess the nature of the pria-
pism (Montague et al, 2003). It is important to ask certain
questions (see Table II). Firstly, the duration of the erection
is needed, as this will determine the risk of future complica-
tions if treatment has not been commenced promptly. It is
important to assess the severity of the associated pain, as
severe penile pain is a more common feature of ischaemic
priapism. Other features to elicit from the history include
determining if there have been any previous episodes that
could lead to identifying the underlying problem. A diagnosis
of stuttering priapism may be considered if there have been
previous episodes. It is important to document any previous
therapies for priapism and their outcome. Eliciting the
patient’s past medical history and use of prescription or illi-
cit drugs (Table I) is important in helping to identify a pos-
sible cause. For example, certain haematological problems,
such as sickle cell disease, increase the risk of priapism.
Finally, any history of recent trauma to the patient’s pelvic,
genital or perineal areas should be noted as injury to these
areas may lead to non-ischaemic priapism. Non-ischaemic
priapism may develop days after the injury due to vessel
spasm or as a clot forms and is slowly resorbed.
Table II. Features to elicit from the patient’s history.
Duration of erection
Severity of pain
Any previous episodes and treatment required
Past medical history including haematological disorders
Drug history (prescribed, ‘over the counter’ or illicit)
History of trauma to the pelvic, genital or perineal areas
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British Journal of Haematology, 2012, 158, 155–164
Review
Physical examination. Ensure genitalia, perineum and abdo-
men are examined to assess for trauma or malignancy (Mon-
tague et al, 2003). The glans penis is typically not affected in
priapism. In ischaemic priapism, the corpora cavernosa are
rigid, compared to the less rigid state in non-ischaemic pria-
pism. It is important to examine for other signs of possible
underlying conditions. In CML, this includes abdominal
examination for hepatosplenomegaly, and for signs of hyper-
viscosity on neurological examination and fundoscopy. The
retina may reveal papilloedema, haemorrhages and venous
obstruction.
Laboratory and radiological investigations. Investigations are
initially performed in the acute setting to assess for ischaemic
or non-ischaemic priapism (Montague et al, 2003). The most
important investigation is blood gas testing. This is where
blood is taken from the corpus cavernosum. Hypoxia is seen
in ischaemic priapism (Table III). Non-ischaemic values are
similar to those of normal arterial blood.
To further help distinguish between ischaemic and non-is-
chaemic priapism, colour duplex ultrasonagraphy can be per-
formed (Aversa & Sarteschi, 2007). In ischaemic priapism,
there will be little or no arterial flow through the cavernosal
arteries. It may also be useful in non-ischaemic patients to
assess cavernosal artery fistula or pseudoaneurysms.
The initial laboratory tests that should be performed
include a full blood count, peripheral blood film, coagulation
studies and urinalysis. These investigations are particularly
important in those with no known predisposing cause for
priapism. A full blood count and blood film will help iden-
tify underlying leukaemias, sickle cell disease and platelet dis-
orders.
Further investigations need to be considered in order to
confirm the underlying cause (Montague et al, 2003). These
will be dependent on the patient’s history and results of
essential investigations listed in Table IV. These include
haemaglobin electrophoresis to detect haemaglobinopathies,
such as sickle cell disease. Psychoactive drug screening and
urine toxicology may be performed to search for any of the
drugs from Table I. If duplex ultrasound shows non-ischae-
mic priapism, pelvic angiography may be performed to iden-
tify the site of a fistula to aid subsequent embolization.
Table III. Typical blood gas results from the corpus cavernosum in
ischaemic priapism.
PO2 PCO2
Source (mmHg) (mmHg) pH
Ischaemic priapism <30 >60 <7·25
(cavernous blood)
Normal arterial blood >90 <40 7·40
Normal mixed venous blood 40 50 7·35
Adapted from the American Urological Association guidelines (Mon-
tague et al, 2003).
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Table IV. Investigations for the cause of priapism
Essential investigations
Penile blood gas
Colour Duplex ultrasound
Full blood count and peripheral blood film
Coagulation screen
Urinalysis
Possible investigations
Haemoglobin electropheresis
Psychoactive drug screening and urine toxicology
Pelvic angiography
Bone marrow studies/molecular studies if suspicion of CML
or other leukaemia
Table V. Investigations to confirm a diagnosis of CML.
Full blood count, manual white cell differential and peripheral blood
film
Bone marrow aspirate and trephine
Cytogenetics, including fluorescence in situ hybridization
Polymerase chain reaction for BCR-ABL1
If the full blood count and blood film suggest CML, then
further investigations to confirm the diagnosis will be
required (Table V).
Management of priapism
The management of priapism is dependent on the type of
presentation and results of blood gas sampling. Priapism in
CML is ischaemic in nature and therefore, we will only
describe the methods in treating this. There is little data
available on the correct management of priapism but the
American Urological Association has published guidelines
based on expert panel discussion and review of the limited
data available (Montague et al, 2003). This has resulted in a
number of recommendations.
Systemic treatment of CML. Because leukaemic priapism is a
relatively rare occurrence and the majority of recent litera-
ture includes small case series, there is no standard treatment
recommended for leukaemic priapism. However, it is
strongly recommended by the American Urological Associa-
tion that systemic treatment of an underlying disorder, such
as CML, should not be undertaken as the only treatment for
ischaemic priapism (Montague et al, 2003). Intracavernous
treatment is required, and should be administered concur-
rently. As ischaemic priapism is a compartment syndrome it
requires treatment directed at the penis primarily. The data
on leukaemia patients presenting with priapism is limited.
Systemic therapies that are commonly used in CML
patients include cytoreductive therapy, such as high-dose
hydroxycarbamide and tyrosine kinase inhibitors (TKIs),
with or without the addition of leukapheresis to reduce
hyperviscosity (Shafique et al, 2007; Adams et al, 2009;
160
Jameel & Mehmood, 2009; Morrison & Burnett, 2011). A
dose of between 2 and 6 g of hydroxycarbamide in up to
four divided doses per day will reduce the white cell count
by up to 60% after 24–48 h (Porcu et al, 2000; Adams et al,
2009). Hydroxycarbamide can be started immediately a diag-
nosis of CML is suspected and continued until the white cell
count has reduced to a safer level. Increasingly, TKIs, such as
imatinib, dasatinib and nilotinib, are being commenced
immediately the diagnosis of CML is confirmed (O’Brien
et al, 2003; Kantarjian et al, 2010; Saglio et al, 2010). How-
ever, often this is a few days after the patient presents
acutely. Imatinib should be commenced at a dose of 400 mg/d
in CP CML, 600–800 mg/d in AP and 800 mg/d in BC
CML. Currently, the availability of the second generation
TKIs, nilotinib and dasatinib, is restricted in the UK. Niloti-
nib has recently been approved for front-line use and should
be commenced at a dose of 300 mg twice daily. In the UK,
dasatinib is only available in a clinical trial for first-line ther-
apy of CP CML (SPIRIT2 in the UK; www.spirit-cml.org). It
is given at a dose of 100 mg once daily. A detailed review of
the efficacies and side effects of TKIs is out with the scope of
this article, and several excellent reviews have recently been
published (Cervantes & Mauro, 2011; Hiwase et al, 2011;
Leitner et al, 2011; Okimoto & Van Etten, 2011).
A number of case series have reported the successful use
of therapeutic leukapheresis to treat priapism (Ponniah et al,
2004; Shafique et al, 2007; Castagnetti et al, 2008; Jameel &
Mehmood, 2009). In the majority of cases, leukapheresis has
been combined with cytotoxic therapy. It is also important
to remember supportive treatment of hyperleucocytosis in
CML with adequate intravenous hydration and allopurinol to
reduce the risk of tumour lysis syndrome. Good thromboem-
bolic prophylaxis with low molecular weight heparin should
also be instituted.
The evidence that chemotherapy or leukapheresis are
effective on their own comes from case reports and small
case series (Rowe & Lichtman, 1984; Morano et al, 2000; Al-
lue Lopez et al, 2004; Ponniah et al, 2004; Shafique et al,
2007; Castagnetti et al, 2008; Jameel & Mehmood, 2009). A
meta-analysis by the American Urological Association found
that three of four patients treated by leukapheresis had reso-
lution of priapism compared to only three of 15 patients
treated with chemotherapy alone (Montague et al, 2003).
Some of these studies that indicated that a conservative
approach is successful had noted detumescence after long
periods of ischaemia, at which point it may have been due to
the progressive natural history of the priapism (Castagnetti
et al, 2008). Although only 35% of cases managed with sys-
temic treatment alone (chemotherapy or leukapheresis)
resulted in erectile dysfunction, a combined modality
approach is recommended without delaying local intracav-
ernous therapy (Montague et al, 2003).
Aspiration. Step-wise management should be performed to
achieve a prompt resolution. Initial intervention may include
ª 2012 Blackwell Publishing Ltd
British Journal of Haematology, 2012, 158, 155–164

therapeutic aspiration (with or without irrigation) or intra-
cavernous injection of sympathomimetics. A penile block
may be performed but is not necessary. If performed, 10–
20 ml of 1% lignocaine is injected below the symphysis pubis
to block the dorsal nerves to the penis. A tourniquet is
applied to the base of the penis. A 16 or 18 gauge biovalve
intra-venous catheter (venflon) can be inserted into the cor-
pus cavernosum laterally through the penile skin, avoiding
the ventral urethra and dorsal neurovasucular bundle. Alter-
natively, the cannula may be inserted through the glans penis
into the corpus cavernosum, which reduces skin bruising. As
the two corpora are interconnected, unilateral aspiration is
sufficient. Twenty to 30 ml of blood is aspirated, and hepa-
rinized saline may be injected. This may be repeated a few
times. Repeated aspirations over 1 h may be needed and up
50 ml of blood can be aspirated. On its own, aspiration has
a success rate of approximately 30%.
Intracavernous sympathomimetics. If ischaemic priapism per-
sists following aspiration/irrigation, intracavernous injection
of sympathomimetics should be performed (Montague et al,
2003; Vilke et al, 2004). This should be repeated prior to sur-
gical intervention. The use of sympathomimetic injections
with or without irrigation has a success rate of 43–81%. The
risk of post-priapism erectile dysfunction also appears
reduced. Phenylephrine is the sympathomimetic agent of
choice due to its lower risk of cardiovascular side effects
(Muruve & Hosking, 1996). Other potential sympathomimet-
ic agents that can be used include adrenaline and metarami-
nol, as listed in the British National Formulary (www.bnf.
org). There are no direct comparison studies between these
agents. Cardiovascular side effects are due to peripheral vaso-
constriction as well as the positive inotropic and chronotropic
effects on the heart. Phenylephrine should be diluted in nor-
mal saline to a concentration of 100–200 lg/ml, and injected
in 1-ml doses every 5 min, up to a maximum of 1 mg. Lower
concentrations should be used in children and patients with
cardiovascular disease. Whilst using sympathomimetic agents,
it is important to monitor for side effects: acute hypertension,
headaches, reflex bradycardia, tachycardia, palpitations and
cardiac arrhythymia. Blood pressure and electrocardiogram
monitoring is recommended in all patients.
Procedures – shunts and penile prosthesis. The use of surgical
shunts should only be considered when sympathomimetic
agents have failed (Hinman et al, 1998; Nitahara & Lue,
1998). A cavernoglanular (corporoglanular) is the primary
choice of shunt procedure due to its ease and fewer compli-
cations. This can be done with a large biopsy needle (Win-
ter) or a scalpel (Ebbehoj) inserted percutaneously through
the glans. If the Winter or Ebbehoj procedure fail, an Al-
Ghorab procedure can still be performed. This involves exci-
sion of both tips of the corpus cavernosa. The shunts will
close with time, but long-term patency may lead to erectile
dysfunction. Erectile dysfunction is more common after
ª 2012 Blackwell Publishing Ltd
British Journal of Haematology, 2012, 158, 155–164
Review
proximal shunts (approximately 50%). These may be per-
formed if there is severe distal penile oedema or tissue dam-
age. A Quackels procedure creates a shunt between the
corpus cavernosum and the corpus spongiosum. A Grayhacks
procedure creates a shunt between the corpus cavernosum
and the saphenous vein. They are difficult procedures with
side-effects including urethral fistula and purulent cavernosi-
tis (Quackels) and pulmonary embolism (Grayhacks) (Kandel
et al, 1968; Ochoa Urdangarain & Hermida Perez, 1998).
Some authorities suggest that if non-operative, or the less
invasive shunt procedures fail, a penile prosthesis is best
inserted before significant intra-corporal fibrosis ensues, after
which this surgery is more difficult and associated with more
complications.
Oral sympathomimetics. Oral systemic therapy is not indi-
cated in acute ischaemic priapism. Oral terbutaline, a beta-
adrenegic agonist, has a response in prolonged erection by
relaxing the corporeal smooth muscles, causing dilation of
the draining veins, and reducing arterial flow (Shantha et al,
1989; Priyadarshi, 2004). There have been reports of the suc-
cessful use of oral terbutaline in a CML patient with pria-
pism following the failure of disease-specific systemic therapy
but not aspiration (Gupta et al, 2009). In the case described,
subcutaneous terbutaline was used. However the rest of the
literature does not support the use of oral sympathomimetic
treatment.
Management of stuttering priapism
Each episode of stuttering priapism should be treated as
above but the aim is to prevent these recurrent episodes
(Montague et al, 2003). Stuttering priapism would be extre-
mely unusual in CML due to effective systemic therapies
available to reduce the white cell count and hence hyperleuc-
ocytosis/hyperviscosity. The main aim in managing stuttering
priapism is to prevent future episodes. This can be per-
formed using oral systemic therapies, self-injection with sym-
pathomimetic agents or surgical penile prosthesis.
Oral systemic therapies. Oral terbutaline has again been tri-
alled in this area but with limited success (Ahmed & Shaikh,
1997). Etilefrine, an a1 selective agonist, has been reported to
be of some success (Virag et al, 1996). However a 2010 trial
using etilefrine and ephedrine failed to show a benefit against
the placebo (Olujohungbe et al, 2011). Digoxin has been
shown not to be effective in this setting (Gupta et al, 1998).
Baclofen was promising in two cases (Rourke et al, 2002).
Hormonal therapies in stuttering priapism suppress serum
testosterone levels by feedback inhibition (diethylstilbestrol),
blocking androgen receptors (antiandrogens) and down-regu-
lation of pituitary gland function (gonadotropin-releasing
hormone agonists) (Montague et al, 2003). They reduce noc-
turnal erections but affect libido and can lead to erectile dy-
function. Diethylstilbestrol can also lead to thromboembolic
161
Review

events and gynaecomastia. These agents are contraindicated
in children who are not fully sexually mature or have not
completed their growth due to their contraceptive effect and
interference with epiphyseal plate closure.
Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor,
has been used as a prophylactic agent (Burnett et al, 2006).
Cavernosal PDE5 levels have been shown to be downregulat-
ed in stuttering priapism (Champion et al, 2005). Sildenafil
increases levels of cyclic guanosine monophosphate (cGMP)
and therefore PDE5 levels also. This reduces episodes of pria-
pism whilst maintaining erections.
Self-injection of intracavernous sympathomimetics. Early self-
injection of phenylephrine at home should be considered
when patients fail or reject systemic treatment for stuttering
priapism (Montague et al, 2003). In these patients the pria-
pism is being treated rather than prevented. Patients should
be counselled about injection sites, dose required and when
to inject in relation to the duration of erection. They should
be taught the potential systemic effects in case inadvertent
systemic administration occurs.
Possible future management options
With the increasing understanding of pathophysiology in pri-
apism, new agents are being considered for development.
Interest exists in therapies targeted at the defective actions of
NO and related erection regulatory molecules (Morrison &
Burnett, 2011). Other possibilities include polyethylene-gly-
col-modified adenosine deaminase therapy, which would
reduce levels of adenosine (Wen et al, 2010), and ornithine
decarboxylase inhibitors, which would block the action of
opiorphin (Kanika et al, 2009).
Management of erectile dysfunction
The main complication following priapism is the potential
development of erectile dysfunction. Aside from causing
physical disability, this can also have a large psychological
effect on patients’ lives. There are guidelines produced by the
American Urological Association on management of erectile
dysfunction (Montague et al, 2005). The current available
therapies for erectile dysfunction include oral PDE5 inhibi-
tors, intra-urethral alprostadil, intracavernous vasoactive
drug injection, vacuum constriction devices, and penile pros-
thesis implantation. A biopsy from the corpus cavernosum is
recommended to confirm muscle necrosis and fibrosis, before
a prosthesis. These methods should be attempted in a step-
wise fashion due to their potential risks and invasive natures.
Conclusions
Although an uncommon presentation in CML, priapism is a
urological emergency requiring urgent therapy. If priapism is
prolonged and goes untreated, then there is a significant risk
of erectile dysfunction in male patients. The treatment of pri-
apism in CML has a multi-disciplinary approach and is likely
to involve some or all of the following hospital departments:
emergency, urology, haematology and clinical apheresis.
Although the majority of the literature is this area are case
reports and small case series, the American Urological Asso-
ciation strongly recommends a combined approach to the
management of priapism in CML, and highlights the impor-
tance of immediate local intracavernous therapy in addition
to the systemic therapy for CML. Increasingly therapeutic
leukapheresis in combination with cytotoxic therapy with
either hydroxycarbamide or a TKI is being used to reduce
the white cell count in patients with hyperleucocytosis and
associated priapism or other features of leucostasis or hyper-
viscosity.
Acknowledgements
MC is supported by a Fellowship from the Scottish Funding
Council (SCD/04).
Conflicts of interest
The authors declare no competing financial interests.

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