Two Forms of Polycythemia Vera: One Indolent, One Aggressive

Jerry Spivak, M.D Professor of Medicine and Oncology Director, Center for the Chronic Myeloproliferative Disorders John Hopkins Interview with:
Jerry Spivak, M.D
Professor of Medicine and Oncology
Director, Center for the Chronic Myeloproliferative Disorders
John Hopkins Medicine

Medical Research: What are the main findings of the study?

Dr. Spivak: The main findings of this study are that polycythemia vera occurs in two clinical forms: an indolent form in which only phlebotomy may be necessary and a more aggressive form requiring myelosuppressive therapy and that these two forms of the disease can be distinguished genetically.

Medical Research: Were any of the findings unexpected?

Dr. Spivak: Based on clinical experience, it was apparent that some polycythemia vera patients only required minimal supportive therapy such as phlebotomy and perhaps aspirin, while others would develop significant extramedullary hematopoiesis with splenomegaly, myelofibrosis and constitutional symptoms, requiring myelosuppression.  However, previously there was no way to identify how the disease would evolve in an individual  patient. We also knew that polycythemia vera behaved differently in women than in men. What was unexpected was that these sex differences had a genetic basis that could be exploited genetically to distinguish polycythemia vera patients with an aggressive clinical course from those with an indolent clinical course.

Medical Research: What should clinicians and patients take away from your report?

Dr. Spivak: Clinicians and patients should understand that polycythemia vera is not a monolithic disorder but can have either an indolent or aggressive clinical course and patients should be treated accordingly. Thus, it is not necessary to subject all polycythemia vera patients to myelosuppressive therapy as is currently recommended.  All polycythemia vera patients should be phlebotomized to reduce and maintain the hematocrit at a sex-specific normal level; treating asymptomatic leukocytosis and thrombocytosis or using hydroxyurea as substitute for phlebotomy is unwarranted.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Spivak: We need to define the genetic basis for acquiring polycythemia vera or the genetic drivers for the two clinical forms of the disease to develop truly targeted therapy.


Two Clinical Phenotypes in Polycythemia Vera
Jerry L. Spivak, M.D., Michael Considine, M.S., Donna M. Williams, Ph.D., Conover C. Talbot, Jr., B.A., Ophelia Rogers, A.A., Alison R. Moliterno, M.D., Chunfa Jie, Ph.D., and Michael F. Ochs, Ph.D.

N Engl J Med 2014; 371:808-817
August 28, 2014DOI: 10.1056/NEJMoa1403141