Case Report: Priapism as The Clinical Presenting Feature of Chronic Myeloid Leukemia: Case Report and 20-Year Literature Review

Introduction

Priapism is a urological emergency due to persistence of an erection lasting more than 4 hours, whether or not it is related to sexual influence.¹ Priapism is a rare condition with an incidence of 1–5 cases per 100,000 people per year. Penile erection in priapism is regularly painless. There are two types of priapism, which are low-flow priapism and high-flow priapism. Low-flow priapism is provoked by a pathological condition of low venous blood flow causing stasis in the penile vessels. This condition is an emergency condition that can result in cell damage and fibrosis, thus it often requires immediate therapy. Meanwhile, high-flow priapism is caused by increased blood flow to the sinusoid arteries without offsetting the flow to the veins. One of the causes of high-flow abnormalities is penile injury, while low-flow priapism is commonly caused by blood disorders such as sickle cell anemia and chronic myeloid leukemia (CML).^2–4

Priapism accounts for 20% of the hematological abnormalities while 1–5% of priapism are due to leukemia. The theory behind a priapism is the dysregulation of nitric oxide (NO) in penile vascularization. This occurs due to changes in NO synthase enzyme activity which decrease NO production by the corpora cavernosa. This ischemic condition induces platelet aggregation, thrombus, and tissue damage. Decreased NO interferes with smooth muscle tone and generates the priapism. Hyperviscosity conditions due to leukocytosis and adenosine-opiorphins abnormalities is also involved in this condition.¹

Currently, the approach to treat CML patients with priapism uses a combination of systemic therapy (chemotherapy with hydroxyurea or tyrosine kinase inhibitors and leukapheresis) and local intracavernosal therapy. Some cases with late manifestations cause erectile dysfunction, gangrene and penile abscess.⁵ This case report and review aims to discuss the clinical characteristics and outcomes of CML patients who experience priapism.

Case

An 18-year-old unmarried male student, presented at the ER complaining of persistent erection of the penis. The patient complained of persistent erected penis for 20 days before admission. There was no phase without an erection in between. Previously, there was neither history of trauma to sexual stimulation, nor consumption of certain drugs. The patient also complained of mild genital pain along with the onset of erection. There were no complaints about discoloration of the penis; becoming reddish, bluish, or pale, also there was no numbness. The patient could urinate normally (see Figure 1).

Figure 1. Penis at day 2, day 6 (after intracavernosal blood aspiration), and day 9.

The patient complained of tinnitus in his right and left ears for 15 days accompanied by blurred vision. The patient also felt that his left side of stomach was slowly enlarging for 5 months. There was no bleeding and fever. Before coming to the ER, the patient was hospitalized at the regional hospital and received a blood transfusion and was diagnosed with a blood disorder.

Physical examination revealed no anemia and icterus. The spleen was palpable showing Schuffner 4 and Hackett 3. There was no enlargement of the lymph nodes. His laboratory findings were hemoglobin 10.4 g/dL; leucocytes 421,000 cells/mm³; platelets 407,000 cells/mm³; white blood cells differential 4.3/6.8/81.3/4.9/2.7; blood urea nitrogen 9 mg/dL; serum potassium 0.5 mg/dL, uric acid 6.5 mg/dL. Peripheral blood smear showed normochromic anemia, normocytic anisopoikilocytosis, leukocytosis (3% myeloblasts, 6% promyelocytes, 4% myelocytes, 2% metamyelocytes, 5% stab neutrophils, 63% segment neutrophils, 4% eosinophils, 6% basophils, 5% lymphocytes, 2% monocytes, atypical lymphocytes (+)) concluded as CML. The patient received hydroxyurea 2000 mg once daily at night, paracetamol 500 mg TID, and an urgent leukapheresis.

The patient underwent leukapheresis once per day (three times since initial admission) with gradual improvement. Unfortunately, on the fourth day of treatment the patient felt a penis erection again with pain on a scale of 0–5. Local examination of the genitalia showed a maximal erected penis, with no discoloration indicative of hyperemia, cyanosis, or pallor. Blood gas analysis showed pH 6.95, pCO₂ 64 mmHg, HCO₃ 14 mEQ/L, BE -18 unit. We concluded that the patient had ischemic priapism. Therefore, the patient underwent intracavernous aspiration producing 150 mL blood. Not long after that, the patient's penis returned to an erection with bleeding from the puncture wound. We then decided to give leukapheresis to the patient.

On the eighth day of treatment, the erection improved with pain scale of 1. Quantitative BCR–ABL examination showed a positive result of 65%, thus the administration of hydroxyurea was stopped and replaced by imatinib 400 mg once daily at night. On the twelfth day of treatment, the erection completely resolved and the patient was successfully discharged from the hospital.

Discussion

This review presents data on patients who have priapism due to CML (see Table 1). Priapism occurred in the age ranging from 9–53. Patients usually had episodes of priapism for 18 h to 7 days. Not all patients with priapism showed a typical clinical examination of CML in the form of splenomegaly, but all of these patients had a hyperleukocytosis profile with a leukocyte count >200,000 cells/mm³. Some of them are equipped with data of peripheral blood smear with excessive blast and identification of BCR–ABL gene. A study by Minckler et al. was the only one reporting a resolved erection with a cold shower, whilst most other cases needed medical intervention.⁶ Although the duration of symptoms varied, four cases reported complications following an episode of priapism. Patients with unfavorable outcomes once received hydroxyurea, imatinib but failed to undergo urological emergency therapy such as intra-cavernosa aspiration, surgical intervention, and embolization.

The patient in our study was 18 years old. However, based on the literature, patients in every age group are at risk of developing priapism. There are two peaks in the age distribution that tend to experience this condition. The peak in earlier age is between 5 and 10 years, especially in patients with sickle cell disease. Meanwhile, the second peak is at sexually active phase between 20 and 50 years. Apart from hypercoagulability, this condition may also be related to the abuse of erectile drugs.⁷

History and physical examination are important when encountering cases of priapism. Laboratory tests are required to check for impaired coagulation and serum electrolytes. Some patients who are at high risk for priapism include users of intracorporal injection therapy for erectile dysfunction, coagulation disorders such as sickle cell disease and CML.^2,4 In CML, hyperleukocytosis is thought to be the prime cause of priapism. The main mechanism is the aggregation of leukemic cells in the corpora cavernosa and dorsal veins of the penis. Other than that, mechanical pressure in the abdominal veins due to the enlargement of the spleen might also increase the risk.¹

The data needed in the management of patients with this case are erection duration, pain scale, trauma, complete blood count, peripheral blood smear, penile blood gas analysis, bone marrow and polymerase chain reaction for BCR–ABL1 if necessary.^1,2,4 In CML, the most common type of priapism is the ischemic one (veno-occlusive). Patients usually complain of painful, rigid erection, with reduced to no cavernous blood flow at all. Priapism that lasts for more than 4 hours indicates a compartment syndrome and may require emergent medical intervention.⁸

The American Urological Association recommends that systemic treatment of an underlying disorder should not be the only one therapy for ischemic priapism. In this case, the patient had an erectile episode since 20 days before the admission. This phenomenon was likely due to the compartment syndrome, hence the intra-cavernous aspiration was required.¹

The intra-cavernous aspiration procedure can be accomplished by giving the anesthetic injection first under the symphysis pubis. The penis is tied with a tourniquet followed by insertion of a 16–18-Gauge bivalve intravenous catheter into the corpus cavernosum. When the two corpora are fused, aspiration of 20–30 mL of blood can be undertaken. This procedure has 30% chances of success.^8,9

Systemic therapy is often used to reduce hyperviscosity is cytoreductive therapy such as high-dose hydroxycarbamide and tyrosine kinase inhibitors (TKI) with or without apheresis procedures. Hydroxycarbamide can be given 2–6 grams divided into four doses per day. This can reduce leukocytes by almost 60% in 24–48 h. In addition, TKI, such as imatinib, can be administered as soon as the diagnosis is confirmed. The recommended dose of imatinib is 400 mg once daily in the chronic phase, 600–800 mg once daily in the accelerated phase, and 800 mg once daily in a blast crisis.⁹ Generally, IRIS study describes the effectiveness of imatinib therapy for complete hematological response (CHR), major cytogenetic response (McyR) and complete cytogenetic response (CcyR).⁴

Leukapheresis can promote a rapid decrease in intravascular leukemic cells, improve tissue perfusion and prevent leukostasis (generally show pulmonary and central nervous system manifestations). Once leukapheresis is given, it possibly can reduce the leukocyte count by 30–60%. However, compared to the chemotherapy, several previous studies have shown that this procedure had high all-cause mortality. According to 2016 apheresis guidelines, category 2 (second-line therapy) is recommended for grade 1B of acute myeloid leukemia (strong recommendation, moderate quality evidence), while category 3 (unclear role of apahresis) is recommended for acute lymphoblastic leukemia cases grade 2C (weak recommendation, low quality evidence). In this guideline, leukapheresis is not recommended for chronic myeloid leukemia.¹⁰ Several cases of priapism in this case review reported a successful combination of leukapheresis with systemic oral CML therapy. A study by Rojas et al. was the only one reporting a failed leukapheresis.

This case report and review presents a comparative presentation of patient characteristics, clinical characteristics of CML, laboratory profile, and therapeutic intervention for CML with priapism. Clinical presentation and early intervention are pivotal keys to achieve favorable outcome and prevent complications. Systemic intervention combined with intraurethral therapy may add the success rate (see Figure 2).

Figure 2. Treatment and outcome from priapism and CML.

Eventually, further discussion and study on other causes of priapism is essential as a meta-analysis stated that priapism might also be related to lymphoproliferative disorders.³²

Consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.