Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 8)

Chronic Idiopathic Myelofibrosis: TreatmentNo specific therapy exists for chronic IMF. Anemia may be due to gastrointestinal blood loss and exacerbated by folic acid deficiency, and in rare instances, pyridoxine therapy has been effective. However, anemia is more often due to ineffective erythropoiesis uncompensated by extramedullary hematopoiesis in the spleen and liver. Neither recombinant erythropoietin nor androgens, such as Danazol, have proved consistently effective as therapy for anemia. Erythropoietin may worsen splenomegaly and will be ineffective if the serum erythropoietin level is 125 mU/L. A red cell splenic sequestration study can establish the presence of hypersplenism, for which splenectomy is...
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Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 8) Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 8) Chronic Idiopathic Myelofibrosis: Treatment No specific therapy exists for chronic IMF. Anemia may be due togastrointestinal blood loss and exacerbated by folic acid deficiency, and in rareinstances, pyridoxine therapy has been effective. However, anemia is more oftendue to ineffective erythropoiesis uncompensated by extramedullary hematopoiesisin the spleen and liver. Neither recombinant erythropoietin nor androgens, such asDanazol, have proved consistently effective as therapy for anemia. Erythropoietinmay worsen splenomegaly and will be ineffective if the serum erythropoietin levelis >125 mU/L. A red cell splenic sequestration study can establish the presence ofhypersplenism, for which splenectomy is indicated. Splenectomy may also benecessary if splenomegaly impairs alimentation and should be performed beforecachexia sets in. In this situation, splenectomy should not be avoided because ofconcern over rebound thrombocytosis, loss of hematopoietic capacity, orcompensatory hepatomegaly. However, for unexplained reasons, splenectomyincreases the risk of blastic transformation. Splenic irradiation is, at best,temporarily palliative and associated with a significant risk of neutropenia andinfection. Allopurinol can control significant hyperuricemia, and hydroxyurea hasproved useful for controlling organomegaly in some patients. The role of IFN-α isstill undefined and its side effects are more pronounced in the older individualswho are usually afflicted with this disorder. Glucocorticoids have been used tocontrol constitutional symptoms and autoimmune complications and mayameliorate anemia alone or in combination with low dose thalidomide (50–100mg/d). Allogeneic bone marrow transplantation is the only curative treatment andshould be considered in younger patients; reduced-intensity conditioning regimensmay permit hematopoietic cell transplantation to be extended to older individuals. Essential Thrombocytosis Essential thrombocytosis (other designations include essentialthrombocythemia, idiopathic thrombocytosis, primary thrombocytosis,hemorrhagic thrombocythemia) is a clonal disorder of unknown etiologyinvolving a multipotent hematopoietic progenitor cell manifested clinically byoverproduction of platelets without a definable cause. ET is an uncommondisorder, with an incidence of 1–2/100,000 and a distinct female predominance, incontrast to the other chronic myeloproliferative disorders. No clonal marker isavailable to consistently distinguish ET from the more common nonclonal,reactive forms of thrombocytosis (Table 103-5), making its diagnosis difficult.Once considered a disease of the elderly and responsible for significant morbiditydue to hemorrhage or thrombosis, with the widespread use of electronic cellcounters, it is now clear that ET can occur at any age in adults and often withoutsymptoms or disturbances of hemostasis. There is an unexplained femalepredominance in contrast to the other chronic myeloproliferative disorders or thereactive forms of thrombocytosis where no sex difference exists. Because nospecific clonal marker is available, clinical criteria have been proposed todistinguish ET from the other chronic myeloproliferative disorders, which mayalso present with thrombocytosis but have differing prognoses and therapy (Table103-5). These criteria do not establish clonality; therefore, they are truly usefulonly in identifying disorders such as CML, PV, or myelodysplasia, which canmasquerade as ET, as opposed to actually establishing the presence of ET.Furthermore, as with idiopathic erythrocytosis, nonclonal benign forms ofthrombocytosis exist (such as hereditary overproduction of thrombopoietin) thatare not widely recognized because we currently lack adequate diagnostic tools. Table 103-5 Causes of Thrombocytosis Malignancy Infection Myeloproliferative disorders: polycythemia vera, idiopathic myelofibrosis,essential thrombocytosis, chronic myelogenous leukemia Myelodysplastic disorders: 5q-syndrome, idiopathic refractorysideroblastic anemia Postsplenectomy or hyposplenism Hemorrhage Iron deficiency anemia Surgery Rebound: Correction of vitamin B12 or folate deficiency, post-ethanolabuseHemolysis