Concurrent polycythemia vera and chronic lymphocytic leukemia: Treatment response to pegylated interferon alpha 2a
Authors: H. Andrew Selinger, Enrique Ballesteros, Robert Bona
Journal: American Journal of Hematology (2013)

Our patient is a 55-year-old male initially diagnosed at age 45 (September 2002) with polycythemia vera (PV). At that time, the CBC showed a Hct of 72%, WBC 11.0/µl, and platelets of 560,000/µl. Phlebotomy treatments resulted in a decrease of the hematocrit to the normal range and a concomitant rise in the platelet count to above 1,000,000/µl. Additional laboratory studies at diagnosis demonstrated erythropoietin level <2.5 U/ml. Subsequent bone marrow biopsy demonstrated marrow cellularity of 70–80%, 1+ reticulin, stainable iron graded as decreased to absent, moderate left shift in myeloid maturation, negative Trichrome staining, and no atypical lymphoid infiltrate. For the subsequent nine years, no complications were reported and phlebotomy was required three to four times annually to maintain a hematocrit <45%. In 2008, the JAK2 V617F allele mutation burden was 65%. During this time period, the WBC count gradually rose to between 25 and 30,000/µl with no immature granulocytes noted. The platelet count plateaued at 1,500,000–1,600,000/µl. The spleen size increased to 16–17 cm. In 2010, an atypical lymphoid aggregate was noted on a bone marrow specimen. Subsequent flow cytometry of the peripheral blood suggested a monoclonal B-cell lymphocytosis. Shortly thereafter, the peripheral WBC count rose to 32,500/µl and the absolute lymphocyte count to 10,300/µl. Flow cytometry demonstrated 70% of the lymphocytes were B-cells positive for CD20 and CD5, and negative for CD10 and CD38. A diagnosis of B-cell chronic lymphocytic leukemia (CLL) RAI stage 0 was made. Additional studies demonstrated IgG VH segment percent homology at 92.70%. FISH analysis was normal. ZAP-70 analysis was indeterminate. In December 2010, the patient experienced a spontaneous hemorrhage in the left calf. After 30 days of hydroxyurea treatment, the platelet count decreased from 1,628,000 to 876,000/µl, and the WBC decreased from 32,500 to 22,500/µl. At this point, the hydroxyurea was discontinued and pegylated interferon alpha 2a (Pegasys) was begun at 45 µg subcutaneously weekly. Over 22 months, at an average Pegasys weekly dose of 72 µg, the WBC decreased from 30 to 7.0K, the absolute lymphocyte count from 10.4 to 2.3, and the platelets decreased to 450K. Phlebotomy occurred twice yearly. Peripheral blood findings demonstrated decrease of JAK-2 allelic ratio V617F/wild type to 30–40%, the monoclonal B-cell population to 12%, and Zap-70 status from indeterminant to negative. Abdominal ultrasound showed decrease in spleen size to 15 cm and bone marrow biopsy from 2012 demonstrated no appreciable change in reticulin (graded as mild). The bone marrow biopsy continued to show lymphoid involvement. Interferon-α is a nonleukemogenic treatment which has been shown in a number of recent studies to yield high rates of hematologic and molecular response in PV with limited toxicity 1. The ability of Pegasys to induce complete molecular responses suggests selective targeting of the malignant clone 2. Earlier clinical studies have likewise demonstrated a beneficial effect in early stage B-CLL using nonpegylated interferon alpha 2a 3. The diagnosis of concomitant CLL/MPN is a rare event and in a recent study analysis of prognostic markers for CLL demonstrated that in patients with a coexistent MPN, lymphoproliferative disorders follow a clinically indolent course 4, 5. Our patient has achieved a substantial hematologic, molecular and splenic response in his PV after 22 months on low dose Pegasys. Moreover, he has achieved a favorable reduction in the B-cell CLL clonal population and a change in Zap-70 status from indeterminate to negative. As far as we know, this is the first report of treatment of concomitant PV and chronic lymphocytic leukemia with Pegasys and the first to demonstrate a positive therapeutic effect on both disorders. H. Andrew Selinger1* Enrique Ballesteros2 Robert Bona3 1Prohealth Physicians, Bristol, Connecticut 06010 2University of Connecticut Health Center 3Frank Netter School of Medicine Quinnipia University