RISK FACTORS: Family history of myeloproliferative disorder (rare), CML - increased incidence in atomic bomb survivors and following radiation treatment of ankylosing spondylitis and cervical cancer
GENERAL MEASURES
. Treatment to relieve symptoms and prevent infections
. Splenectomy has no impact on mortality, but is occasionally done for symptomatic relief. Extreme thrombocytosis, progressive and massive liver enlargement may ensue.
. CML
. Molecularly targeted therapy (with imatinib mesylate)
. Chemotherapy (for advanced phases of the disease)
. Bone marrow transplantation is the only known curative option, with disease-free survival in 50-70%, and should be offered to young patients with HLA matched donors
. CIMF
. No standard therapy
. Rule out other treatable causes for anemia
. Radiotherapy for symptomatic extramedullary hematopoietic tumors, or symptomatic splenomegaly
. Successful bone marrow transplantation leads to the reversal of established fibrosis, and is the only known
potential cure
. ET
. Young, asymptomatic patients with platelet count <1,500,000/uL generally not treated
. Lower the platelet count in those > 60, history of thrombosis, or with other cardiovascular risk factors, or platelet count > 1,500,000/uL
DIET Maintain good nutrition
PATIENT EDUCATION
β’ Explanations about the disorder, treatment protocols, lab studies, and prognosis
β’ Symptoms of recurrence to watch for
β’ Importance of followup examinations
DRUG(S) OF CHOICE
. CML
. Imatinib mesylate (Gleevec), a potent inhibitor of the ABL tyrosine kinase, produces complete hematologic
remissions in 95% and major cytogenetic remissions in 87% of newly diagnosed patients in chronic phase.
Dosage - 400 mg/day in chronic phase CML, 600-800 mg/day in accelerated/blast phase disease
. Interferon alpha produces 55% complete hematologic remissions, and 35% major cytogenetic remissions and has largely been replaced by imatinib as the treatment of choice for most patients
. Allopurinol to control hyperuricemia - begin prior to hydroxyurea therapy
. Hydroxyurea may be useful for controlling the excessive myelopoiesis at initial diagnosis in chronic phase
disease, in conjunction with imatinib
. Accelerated phase and blast crisis are usually treated with regimens designed for the treatment of acute
leukemia. Imatinib mesylate induces hematologic remissions in 50% of patients with myeloid blast crises and major cytogenetic remissions in 16%. These responses tend to be transient in duration.
. ET
. Hydroxyurea generally favored over alkylating agents for control of thrombocytosis, as it has little to no Known leukemogenic potential
. Anagrelide may also be used to control thrombocytosis, particularly in younger patients with ET
. Interferon is also useful for cytoreduction and can be used safely in pregnancy
. CIMF
. Anemia is treated with transfusions as required. Androgenic steroids - fluoxymesterone (Halotestin) 10 mg bid and prednisone 0.5 mg/kg/d may be useful for anemia. Erythropoietin, in patients with endogenous EPO levels of less than 100 IU/mL, and danocrine (Danazol) have also been used for treatment of anemia.
. Hydroxyurea is useful for control of splenomegaly, thrombocytosis and leucocytosis
. Investigational drug therapy should be considered since there is no standard therapy that signifi cantly
impacts mortality
ALTERNATIVE DRUGS
. CIMF
. Androgens and glucocorticoids may improve anemia
. Corticosteroids if autoimmune hemolysis present
. ET
. Aspirin, with or without dipyridamole, may prove useful in preventing thrombotic or ischemic symptoms in
some patients
. Erythromelalgia (described below) responds to rapid reduction of the platelet count or to administration of
nonsteroidal anti-infl ammatory agents
PATIENT MONITORING Individualized and dependent on therapy, ongoing studies, and stage of the illness
POSSIBLE COMPLICATIONS
. Transformation to acute leukemia
. Gout due to hyperuricemia
. Uric acid nephropathy
. CIMF
. Portal hypertension
. Splenic infarcts
. Budd-Chiari syndrome
. Pulmonary hypertension
. Pleural or peritoneal effusions due to extramedullary hematopoiesis (EMH)
. Paraspinal /epidural EMH
. ET
. Thrombohemorrhagic complications in one third
. Erythromelalgia (a vaso-occlusive syndrome with localized pain, burning, warmth of distal extremities
- may progress to gangrene)
EXPECTED COURSE/PROGNOSIS
. CML
. Median survival > 5 years from the time of diagnosis, approximately 12-18 months after development of the
accelerated phase, and 3-6 months after developing blast crisis
. Adverse prognostic factors include advanced age, degree of splenomegaly, elevated platelet count, degree of leukocytosis, presence of blasts or of large numbers of eosinophils or basophils, percent of immature cells in the marrow, and clonal evolution
. 85% will die in blast crisis
. CIMF
. Progressive splenomegaly, anemia and thrombocytopenia
. Median survival is 5 years from the time of diagnosis
. Usually die of hemorrhagic or thrombotic complications and infections, 10-20% terminate in a rapidly progressive form of acute leukemia
. Adverse prognostic factors include hemoglobin of less than 10 gm/dL, leucocytosis (> 30,000/uL) or
leukopenia (<10,000/uL), presence of peripheral circulating blasts, complex cytogenetic abnormalities, and hypercatabolic symptoms
. ET
. Overall life expectancy only slightly shortened. Some studies indicate no significant difference in survival
between patients and age/sex matched controls.