Malignancies 1 Flashcards
patho in myeloproliferative neoplasms
overproduction of formed and matured blood elements (not precursors) without significant dysplasia
(looks normal but will continue proliferating)
when blood is being produced elsewhere not just in the bone marrow
extramedullary hematopoiesis
patients with mpns also have ___ and are at risk for ___
have myelofibrosis, at risk for acute leukemia transformation
characteristics of polycythemia vera
clonal disorder involving multipotent hematopoietic progenitor cells
accumulation of phenotypically normal rbc, granulocytes and platelets
pathophysio in pv
jak2 mutation that makes activates continuous proliferation
s/sx of pv
incidental finding high hemoglobin or hematocrit aquagenic pruritus hyperviscosity splenomegaly constitutional symptoms erythromelagia thrombotic episodes hemorrhagic episodes low serum epo
diagnostic criteria for pv
hg, hc or increased red cell mass
relative erythrocytosis
hemoconcentration secondary to dehydration, diuretics, ethanol abuse, androgens, or tobacco use
absolute erythrocytosis
hypoxia, tumors, renal disease, drugs, familial, pv
what happens in renal artery stenosis
blood is not gonig in kidney -> organ feels that it’s not getting enough o2 -> production of epo and blood
patho in hypernephroma or pheochromocytoma
tumors can produce catecholamines -> stress -> more rbc production
complications of pv
hyperuricemia
thrombotic complications
progression to myelofibrosis (spent phase)
progression to aml
treatment goals for pv
men: hgb = 14 g/dl or hct <45%
women hgb = 12 g/dl or hct <42%
treatment for pv
phlebotomy hydroxyurea (ribonucleotide reductase inhibitor) interferon alpha chemo with alkylating agents radioactive phosphorus (32p) aspirin/clopidogrel ruxolitinib
least common myeloproliferative neoplasm
primary myelofibrosis
characteristics of primary myelofibrosis
jak2, mpl, calr
reticulin fibers in bone marrow
extramedullary hematopoiesis (spleen –> splenomegaly)
constitutinal symptoms of primary myelofibrosis
loss of appetite due to compressed stomach caused by splenomegaly
nausea
pruritus, bone pain, night sweat
peripheral blood smear in primary myelofibrosis
leukoerythroblastic picture
tear drop cells
nucleated red cells
immature wbcs
bone marrow with silver stain in primary myelofibrosis
presence of reticulin fibers
occupy space for hematopoiesis –> pancytopenia
disorders causing myelofibrosis
malignant and nonmalignant, table 3
how to diagnose primary myelofibrosis
all 3 major criteria and 2 minor criteria, table 4
symptoms of primary myelofibrosis
decreased quality of life
increasing marrow failure leading to transfusion dependent anemia
progression to acute myeloid leukemia
therapy for primary myelofibrosis
corticosteroids for low platelets danazol for hgb interferon alpha ruxolitinib to regress spleen and reduce cytokines allogeneic bone marrow transplant**
disease that results from clonal mutations that lead to the overproduction of mature platelets
essential thrombocythemia
characteristics of essential thrombocythemia
- clonal disorder involving hematopoietic progenitor cells
- accumulation of phenotypically normal platelets
- mutations in jak2 v617f, mpl, and calr
causes of thrombocytosis
tissue inflammation (collagen vascular disease, ibd) malignancy infection myeloproliferative disorders myelodysplastic disorders postsplenectomy or hyposplenism hemorrhage iron deficiency anemmia surgery rebound hemolysis familial
diagnostic criteria for essential thrombocythemia
7 items, table 5
effects of essential thrombocythemia
high platelets –> at risk for hemorrhagic episode because of consumption of all the von willebrand factor
treatment for essential thrombocythemia
platelet pheresis
hydration
treatment for hemorrhagic episodes in essential thrombocythemia
hydroxyurea* anagrelide to inhibit megakaryocyte differentiation* interferon alpha alkylating agents antiplatelet agents*
essential thrombocythemia can lead to ___ and ___
myelofibrosis and aml
essential thrombocythemia low risk
age <60 and no prior cv event
m: nil or low dose aspirin
essential thrombocythemia intermediate risk
generic cv risk factors
m: low dose aspirin
essential thrombocythemia high risk
age >60 with prior cv event
m: myelosuppression + low-dose aspirin
characteristics of myelodysplastic syndrome
heterogenous group of myeloid disorders
- lead to cytopenia
- then bone marrow failure
can produce blood cells but ugly and ineffective leading to cytopenia
high risk for aml
dysplastic features in myelodysplastic syndrome
binucleated rbcs
myeloblast in peripheral smear
hypersegmentation of neutrophils
treatment for myelodysplastic syndrome
transfusion, chelation hematopoietic growth factor demethylating agents lenalidomide immunosuppression chemo allogeneic stem cell transplantation!!
t/f younger people are excluded from getting aml
false
risk factors for aml
hereditary, radiation, drug, chemical or other occupation exposure, idiopathic
features of aml
anemia: easy fatigability leukopenia/leukocytosis leukocyte dysfunction: fever, susceptibility to infections thrombocytopenia: bleeding, hemorrhages organomegaly
peripheral smears of aml
very large myeloblasts
peripheral smear of acute promyelocytic leukemia
stick like figure called rods in faggot cells
butt cells
better risk results in cytogenic testing of aml
inv 16, t(16,16), t(8,21), t(15,17)
very responsive to treatment, 55-65%
intermediate risk in cytogenic testing in aml
normal cytogenetics, t(9,11)
24-40%
poor risk in cytogenic testing in aml
complex karyotypes, deletion of 5, 7, 5q, 7q
very aggressive treatment, 5-14%
most important diagnostic test for aml
cytogenic testing
other diagnostics for aml
pretreatment evaluation morphology (smear) cytochemical analysis (myeloperoxidase, nonspecific esterase) immunophenotyping flow cytometry cytogenetics
principle of flow cytometry
determines the cell signature of the leukemia for classification via CD antigens
dictates prognosis and treatment
definitive antigens used for aml
cytoplasmic mpo
antigens used for all b-cell
cytoplasmic cd 79a, cd22, cd19, cd10
definitive antigens used for all t-cell
cytoplasmic cd3
surface cd3
t cell receptor
treatment for aml
first determine fitness (young, good cv = chemo)
phases of chemo for aml
induction phase
- induce remission, eliminate cancer
- anthracycline + cytarabine
- demethylating agents, bcl inhibitors
consolidation phase
- prolong remission
- high dose cytarabine or hematopoietic stem cells (allegeneic)
phases of chemo in apl
induction
- all trans retinoic acids, arsenic trioxide, anthracycline
consolidation phase
- atra, arsenic trioxide, anthracycline
maintenance phase
-tablets, supportive therapy
risk factor for chronic myeloid leukemia
radiation
15% of all leukemias
patho in chronic myeloid leukemia
formation of philadelphia chromosome = bcr-abl gene combination
–> new tyrosine kinase
downstream signaling pathways in cml
table 10
features of cml
asymptomatic anemia splenomegaly thrombotic or vaso-occlusive events due to high wbcs blastic accelerated phase
chronic phase of cml
<10% of the cells in the blood and bone marrow are blast cells (immature)
accelerated phase of cml
table 11
blast crisis/ blast accelerated phase of cml
blasts are >20% of peripheral blood wbc or nucleated bone, like acute leukemia
peripheral blood smears in cml
numerous wbc apparent
wbcs are mature (aml = immature)
treatment options for cml
leukapheresis/hydroxyurea (not definitive treatments) tki interferon alpha (pregnant) chemo (blastic phase) bone marrow transplant (blastic crisis)
indication for imatinib
all phases
indication and toxicity of dasatinib
i: all phases
t: pleural and pericardial effusions, pulmo hpn
indication of nilotinib
all except blastic
t: vasoocclusive disease, pancreatitis
indication for bosutinib and ponatinib
all except frontline
ponatinib: skin rashes
indication for omacetaxine mepesuccinate
failure of >2 tki
(cml) partial cytogenetic response is expected by ___
3rd month
<35% cells should be neg for philadelphia chromosome
(cml) expectation by 6th month
complete cytogenetic response or complete absence of philadelphia chromosome
(cml) expectation by 12th month
major molecular response, pcr neg for leukemic products
molecularly undetectable leukemia
