Post–polycythemia vera myelofibrosis with myelodysplastic-like progression in a patient with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in the modern world, caused by relentless accumulation of CD5+ B lymphocytes in the blood, bone marrow, and secondary lymphoid organs.¹ Polycythemia vera (PV) is a Philadelphia chromosome–negative myeloproliferative neoplasm.² These 2 conditions rarely coexist, with only a few cases reported in the literature.³ Here, we describe a case of indolent CLL complicated by PV and then post-PV myelofibrosis.

An 82-year-old man with indolent CLL, who had not required treatment since his diagnosis 5 years prior, presented to a hospital with fatigue, hyperhidrosis, and weight loss of 20 kg over a 2-year period. No abnormalities were detected on physical examination. His blood results showed hematocrit of 60.1% (reference range [RR], 40%–54%) and elevated lactate dehydrogenase, β-2 microglobulin, C-reactive protein, and uric acid levels. He underwent venesection without complications. Other tests showed 76% pathological B lymphocytes: CD19+, CD5+, CD79b(–), CD23+, CD200+, CD20+, CD43+, κ free light chain(+). Positive V617F mutation was found in the JAK2 gene, and chromosome 13 and the TP53 gene deletion (17p13) was recorded. In addition, a substitution in the CEBPA gene was detected. No other karyotype abnormalities were found. Erythropoietin was also low (2.53 mU/ml; RR, 4–26 mU/ml). Computed tomography showed hepatosplenomegaly but no enlarged lymph nodes. CLL accompanied by PV was suspected, and trephine biopsy along with cytogenetic tests were performed. The patient was discharged and prescribed aspirin, allopurinol, and folic acid. He was readmitted the following month with elevated red blood cell count and hematocrit; therefore, another venesection was performed. Three months later, he was admitted to the hospital yet again and a positron emission tomography scan showed an active metabolic process in the bone marrow, possibly related to the primary disease. Deranged metabolism of the liver and spleen was also noted. The trephine biopsy showed coexistence of 2 pathologies, CLL and post-PV myelofibrosis with myelodysplastic-like progression (Figure 1A–1D). Treatment with ruxolitinib was commenced. Subsequently, during another routine appointment, the patient was anemic, required admission and blood transfusion, and further doses of ruxolitibib were reduced by 50%. Three months later, he was readmitted with neutrophilia (23 g/l; RR, 2.5–7 g/l) and worsening general status. An assumption of the disease acceleration was made.

The patient underwent another trephine biopsy. A month later, he was readmitted with profound anemia, in poor general condition, with shortness of breath on exertion, and enlarged abdomen. Ultrasound showed hepatosplenomegaly. He required blood transfusion, broad spectrum antibiotics, steroids, and darbepoetin, and was deemed ineligible for treatment with fedratynib. As the patient’s condition improved, he was discharged home to continue his previous treatment regimen with surveillance.

The mechanism and pathology underlying the coexistence of CLL and PV are not fully understood.³ As suggested in a retrospective analysis,³ patients with concomitant CLL and PV usually have an indolent lymphoproliferative disease, and in most cases they have not previously received chemotherapy. This may suggest that rather than being caused by the leukemogenic effect of chemotherapy, it may be associated with immunodeficiency inherent to CLL.³ Despite this, there is ample evidence to prove that TP53 deletion is a negative predictive marker in CLL,⁴ and this has also been described as a risk factor for acceleration in PV.² It was acknowledged in the literature that 13q deletion plays a significant role in CLL and PV development.⁵ These rare occurrences require further study to assess the molecular pathology and epidemiology.