Coexistence of a myeloproliferative disorder and secondary polycythemia in the same patient
Authors: Eirini Kouroupi
Journal: American Journal of Hematology (2012)

Differential diagnosis between primary and secondary polycythemia has been simplified by the detection of JAK2 gene mutations, which confirms the presence of a clonal erythroid hyperplasia, and thus the diagnosis of polycythemia vera (PV). [1] In the absence of detectable JAK2 gene mutations, myeloproliferative disorder (MPN) diagnosis relies on minor criteria including low circulating levels of erythropoietin (EPO), endogenous growth of colonies and specific histopathological features on a bone marrow biopsy specimen. Treatment of PV patients with hydroxyurea is usually rapidly efficient and resistance to cytoreduction is rarely observed [2]. We report herein a clinical observation where a JAK2 V617F positive MPN occurred concomitantly with a secondary polycythemia, thus causing an unexpected resistance of the erythroid proliferation to hydroxyurea, fullfiling the ELN criteria [2]. A 93-year-old Caucasian man was referred to our outpatient clinic for severe headaches, dizziness, and recent increase in blood cell counts. Review of systems failed to reveal any major complaints except for severe itching after warm bath. The patient's medical history included an ischemic cardiopathy, which improved after a coronary by-pass and an implant of a pacemaker, an asymptomatic Paget's disease, a moderate chronic renal insufficiency and a hypothyroidism while family history had no particularity. Physical examination did not reveal any abnormal findings, including splenomegaly. Hematological parameters at presentation showed an increase in all myeloid lineages: Hemoglobin: 18.2 g/dl, hematocrit: 53.8%, leucocytes: 16 g/l with 13.8 g/l neutrophils and platelets: 650 g/l. Molecular analyses of leucocyte DNA revealed the presence of the JAK2 V617F mutation (with an allele burden of 45%) leading to the diagnosis of an MPN. Because of age and hyperviscosity syndrome, the patient was immediately put on a phlebotomy program and Hydroxycarbamide (2 g daily). However, after 8 months of treatment, the response was unsatisfactory with persistently elevated Hb (16 g/dl) and HCT (50%) despite normalization of platelet and leucocyte counts (to 200 and 8 g/l, respectively). Additional biological studies in view of investigating this apparent resistance of erythroid proliferation to hydroxycarbamide revealed a high level of EPO (89 IU/l with a normal value corrected for HCT at < 10 IU/l) while abdominal ultrasonography and contrast-enhanced abdominal computed tomography showed bilateral multiple large cystic masses (up to 10 cm in diameter) suggesting the presence of a polycystic kidney disease [3], despite the absence of hypertension and other clinical complaints. Secondary polycythemia with high EPO levels in cyst fluid and blood plasma have been reported in patients with autosomal dominant polycystic kidney disease [4]. On the basis of these observations, we encourage and confirm the systematic determination of serum EPO either at the time of diagnosis of a MPN or in the presence of an unexplained resistance to treatment in MPN patients with a JAK2 V617F mutation, to avoid missing the infrequent but possible simultaneous occurrence of a secondary polycythemia and an unnecessary increase of cytoreduction. EK performed the study and wrote the paper; BC analysed the data and wrote the paper; CD and MHS contributed essential data; JJK analysed the data; and CC designed the study and wrote the paper. Eirini Kouroupi*, * Hopital Saint-Louis, Unité de Biologie Cellulaire 1, Av. Claude Vellefaux, Paris, France.