Priapism as Presenting Manifestation in a Case of Pediatric CML

An 8-year-old boy with a 3-day history of tense, rigid, and painful penis presented to the urology department. There was no history of trauma or medication use. The physical examination showed splenomegaly and laboratory investigations revealed leukocytosis with left shift, suggesting the possibility of a myeloproliferative neoplasm. The patient underwent corporal-glandular shunt surgery for priapism, successfully resolving the condition. However, the further evaluation indicated pediatric chronic myeloid leukemia (CML). Treatment with Dasatinib achieved a complete hematologic response within one month. This case is a reporting of rare phenomena of CML and priapism as a presenting feature in a pediatric patient and a comment on the treatment challenges of Pediatric CML.

Chronic myeloid leukemia (CML) is a clonal hematologic disorder characterized by the presence of the Philadelphia chromosome, an abnormally shortened chromosome 22 caused by a reciprocal chromosome translocation t (9;22) (q34; q11). This translocation combines the ABL gene on chromosome 9 with the BCR gene on chromosome 22, creating the chimeric BCR-ABL mRNA. Clinically, CML can be divided into three phases. The initial phase is chronic, characterized by the expansion of myeloid progenitor cells showing normal differentiation. Subsequently, if left untreated or treated inappropriately, chronic CML might turn into accelerated phase or acute phase called as blast crisis [1].

In Western registries, the median age at which chronic myeloid leukemia (CML) is diagnosed is 60 to 65 years. CML is relatively rare in the pediatric population, comprising approximately 2% of all leukemias in children under 15 years and 9% in adolescents aged 15 to 19 years. The annual incidence in these age groups is approximately 1 and 2.2 cases per million, respectively. Due to the limited occurrence of CML in children and adolescents and the scarcity of robust clinical trial data, we lack well-established practice standards for managing pediatric CML [2]. Priapism is described as a pathological erection of the penis that lasts more than four hours. It has a diverse etiology and is categorized into three primary types: ischemic, stuttering, and non-ischemic/traumatic. Ischemic priapism is the most frequent, with more than 50% of instances caused by sickle cell disease and 20

An 8-year-old boy was admitted to the urology department with a complaint of a tense, rigid and painful penis for three days without any history of trauma, medication use or prior episode. Past medical history was inconclusive, with average growth and development. The physical examination was unremarkable except for notable splenomegaly 2 cm below CM. Laboratory investigations are displayed in Table 1.

Table 1: Patient's Laboratory investigations

In view of abnormal counts, hematology referral was sought and in the meantime the urologist performed a corpora-glandular shunt surgery for the priapism after unsuccessful intracavernosal aspiration and phenylephrine injection attempts. Priapism was resolved after surgery, but since physical examination and laboratory findings suggested the presence of myeloproliferative neoplasm, likely in the form of chronic myeloid leukemia, a bone marrow biopsy and BCR-ABL assay was done, results of which confirmed a diagnosis of pediatric CML-CP (BCR-ABL1 86.860% IS). The Philadelphia chromosome was positive on cytogenetics and ELTS score was 0.8222 (Low risk category). Dasatinib 50mg was prescribed for the patient, and the patient achieved a complete hematological response in 1 month. Patient recently completed 2 months on dasatinib and remains asymptomatic. He is planned for BCR-ABL assay at 3 months of therapy.

Chronic myeloid leukemia is a well-known and common disease occurring in older adults, but it is infrequent in the pediatric population, especially in children under 15 years, with an estimated 1 case per million per year [2]. Even rarer is the presentation of priapism as the first presenting feature in chronic myeloid leukemia. Priapism can be of ischemic low flow or stuttering type and is rarely high flow in these cases. Although if present, it is primarily the first presenting sign rather than a disease complication or progression. Most patients present within a few hours to weeks of the onset of priapism with more common findings of splenomegaly, anemia and thrombocytosis than the regular counterpart. The mean age at presentation of priapism was 27.4 years in a study by Ali et al. [5].

Our patient was an 8-year-old boy who presented with priapism for which he underwent corporoglandular shunting after unsuccessful intra-cavernosal aspiration and phenylephrine injection attempts. In a case by Clark et al. a similar pathway was noted [6]. The primary blood investigations at admission pointed towards CML, and subsequent investigations confirmed the same.

Since the advent of second-generation TKIs (tyrosine kinases inhibitors) like dasatinib (60 mg/m2 once daily to a maximum dose of 100 mg) and nilotinib (230 mg/m2/dose twice daily, with a maximum single dose of 400 mg), they are used as first-line compared to first generation imatinib (340-600 mg/m2/day), as they are expected to lead to quicker and more profound molecular responses in chronic myeloid leukemia (CML) patients. However, their use does not appear to influence disease-free survival outcomes significantly [7]. Allogenic stem cell transplantation is now considered to be a third-line option [8]. 

However, children undergoing TKI treatment encounter distinctive side effects, such as growth disturbance, not commonly observed in adults. While discontinuing TKIs in adults with a deep and sustained molecular response is feasible, the same approach could be more advantageous in pediatrics to minimize TKI-related side effects, although data are limited. Considering potential future TKI discontinuation, second-generation TKIs serve as a favorable first-line therapy for children who may require discontinuation, given their faster response induction compared to Imatinib [8]. Thus, we also started our patient on Dasatinib considering these points.

Nonetheless, at present, there still exists a paucity of evidence-based guidelines for the diagnosis and management of pediatric chronic myeloid leukemia (CML). As for monitoring in pediatric CML, The National Comprehensive Cancer Network (NCCN) guidelines advise conducting QRT-PCR every three months for the initial three years, and subsequently, at intervals of every 3 to 6 months [7]. We're also planning to monitor our patient adhering to the guidelines excusing any non-compliance on the patient's end, which is fairly common in patients of developing countries like ours.

This case underscores the rarity of pediatric chronic myeloid leukemia (CML) and highlights the infrequency of priapism as a presenting symptom, especially in pediatric patients. Moreover, it emphasizes the lack of well-established treatment guidelines for pediatric CML. Early recognition of such atypical presentations and the need for individualized management are crucial for better outcomes in this uncommon scenario.