What is chronic myelogenous leukemia?
-uncontrolled production of maturing granulocytes, predominantly neutrophils, but also eosinophils and basophils
-1973: philadelphia chromosome balanced reciprocal 9;22 translocation
-1980: BCR-ABL gene and protein were characterized
-1990's: BCR-ABL protein is a constitutively activated tyrosine kinase
What is the epidemiology of CML?
-accounts for 15-20% adult leukemia
-annual incidence of 1-2 cases per 100,000
-slight male predominance
-median age 50y/o
-ionizing radiation only known risk factor
What is the chronic phase of CML?
-used to last 4-6 yrs. Now?
-85% of pts present this way
What is the accelerated phase of CML?
-neutrophil maturation progressively worse
-more difficult to control
What is blastic phase=acute leukemia?
-survival few months
What are the clinical findings for the chronic phase?
-symptoms: fatigue, malaise, wt loss, abd fullness/discomfort, bleeding, shoulder or sternal pain, gout
-splenomegaly (75%), hepatomegaly
What are the lab findings in CML?
-peripheral blood- neutrophilia (ANC). neutrophilia, basophilia, anemia, thrombophilia, eosinophilia. WBC 50-800k, may have blasts <15%, low LAP scores, increased B12 level
-marrow: hypercellular, erythroid hyperplasia, <30% blasts
How do you diagnose CML?
-gold standard=philadelphia chromosome
What are the tyrosine kinase inhibitors?
-imantinib: heme, GI, liver, edema
-Nilotinib: heme, GI, liver, QT prolongation (K, Mg, periodic EKG)
-Dasatinib: heme, GI, liver, EDEMA (may need echo)
What are the side effects of tyrosine kinase inhibitors?
-fluid retention: pericaridal, pleural, peripheral (diuretics)
-rash: topical steroids, abx
-cramps: Ca, tonic
What are some important points about CML?
-used to be a fatal dz within 5 yrs. With newer oral therapy meds, survival is extending.
-primary care issues: med compliance, med side effects, med drug interactions
What is the incidence of chronic lymphocytic leukemia?
-most common leukemia in western countries
-median age 70
-jewish ancestry: rare in asians
What are the symptoms of CLL?
-asymptomatic in 25%
-10% present with B symptoms: unintentional wt loss, fever, fatigue, night sweats.
-most with fluctuating lymphadenopathy
-unusual: autoimmune, anemia, recurrent infections
What is the staging and prognosis for CLL?
-0= lymphosytosis, 12.5 yrs
-1= lymphadenopathy, 8.5 yrs
-2=splenomegaly +/- hepatomegaly, 6 yrs
-3=anemia, 3 yrs
-4= thrombocytopenia, 1.5 yrs
What are the clinical features of CLL?
-usually asymptomatic, 40-50% splenomegaly, +/- hepatomegaly
-infections: hypogammaglobulinemia complement deficiencies, defects in opsonization (strep, staph, hemophilus, compounded by treatments)
-make sure up to date on immunizations
How do you diagnose CLL?
-suspect when absolute lymphocyte count is high and sustained. mature lymphocytes in peripheral blood. mature lymphocytes >30% of marrow cells. lymphocytes are phenotypically identical and consistent with CLL
What are you differential dx's of lymphocytosis?
-lymphoproliferative disorders: flow cytometry of peripheral blood to distinguish between benign and malignant lymphocytes
What is the treatment for CLL?
-not curable leukemia
-when to treat? "smoldering leukemia". hgb >13, ALC <30k, plt >150k, <80% lymphocytes on bone marrow
What are indications for treatment for CLL?
-disease related symptoms: B symptoms, organomegaly, recurrent infections
-impaired bone marrow function
-rapid doubling time of the ALC
What is multiple myeloma?
-cancerous growths of a single clone of plasma cells
-typically procude monoclonall immunoglobulin fragments
-skeletal destruction with hypercalcemia
What is the etiology of multiple myeloma?
-numerous risk factors; cause unknown
-radiation, chronic immune stimulation, benzene and pesticide exposure, some familial clusters
What is the epidemiology of multiple myeloma?
-1% of all cancers
-lower incidence in asians
-twice as common in blacks than whites
-median age at dx: 66 yrs old
What are clinical features of multiple myeloma?
-history: bone pain, weakness and fatigue, weight loss
-exam: pallor, decreased height, infection, skeletal tenderness
What is the diagnostic workup for multiple myeloma?
-CBC, CMP (calcium, renal function, golbulin fraction)
-serum and urine electrophoresis with IPEP that documents a monoclonal gammopathy (quantitative immunoglobulins, skeletal survey- no bone scan, bone marrow aspirate and biopsy)