Leukemias Flashcards
how do we diagnose leukemias?
by whether they are chronic or acute
by what the prominent cell type is and the stage of maturation
what does a bone marrow biopsy give you that is important?
architecture and pattern of involvement
T cell CD markers
1,2,3,4,5,7,8
CD13/15 cell
granulocyte
CD14 cell
monocyte
B cell CD markers
19,20,21,22,23
CD34 marker
stem cell
CD33 marker
myeloid
in flow cytometry what does side scatter measure?
complexity of the molecule…so if the cell has tons of antigens will have higher side scatter
in flow cytometry what does forward scatter measure?
how big is the cell
what can fluorescence tell you in flow cytometry?
can be used to label for specific cell markers and determine the cell type based on these
CML
chronic myelogenous leukemia
CML classification and disease associations
myeloproliferative disorder
P vera
essential thrombocytosis
primary myelofibrosis
what specific cell has gone awry in CML?
hematopoietic progentior cell…with a mutation that pushes it to the myeloid side and not lymphoid
common symptoms and presentation of CML
fever, weight loss, early satiety, sweats, fatigue
often an asymptomatic patient with high white count
PE findings for CML
splenomegaly and hepatomegaly
common lab findings in CML (3)
leukocytosis with basophils eosinophils and PMNs
Anemia
thrombocytosis
what will you see on the bone marrow aspirate in CML? and what about biopsy?
increased M:E ratio
hypercellular
not much fat…lots of granulocytes
what to see on smear with CML?
immature granulocytes and basophilia
what genetic change is required for CML?
Philadelphia chromosome…translocation (9;22) Bcr-Abl regions together
how do we see the t(9;22)??
either with FISH or cytogenetics (karyotyping)
how else can we pick up the t(9;22)?
quantitative PCR for the Bcr-Abl regions
CML phases
chronic-3-5 years
accelerated- 6-9 months (luekocytosis, splenomegaly)
blast crisis- survival about 5 months
blast crisis of CML characteristics
worsening symptoms with leukocytosis
cytopenias cause issues like anemia and infection
extramedullary diseases
is the blast crisis of CML, AML or ALL?
can actually be either because the progenitor cell will pass on to both the myeloid and lymphoid cell lines
best treatment for CML?
Abl tyrosine kinase inhibitors…Imatinib mesylate
CLL
chronic lymphocytic leukemia
what cell is CLL a malignancy of?
mature B cells…homogeneous population of mature B lymphocytes
What is the most common adult leukemia?
CLL
risk factor for CLL?
having a family member with CLL
symptoms of CLL at presentation
fevers, sweats, fatigue, weight loss, early satiety
FREQUENT INFECTIONS
4 lab findings in CLL
luekocytosis high lymphocytes
anemia
thrombocytopenia
hypogammaglobulinemia
hypogammaglobulinemia in CLL, why?
because malignant B cells are being made and they are not cranking out the good immunoglobulins
PE findings for CLL
hepatomegaly, splenomegaly and lymphadenopathy
autoimmune disorders in CLL
autoimmune hemolytic anemia and immune thrombocytopenia
smear findings in CLL
tons of lymphocytes…diagnostic
aspirate findings in CLL
lots of maturing lymphocytes, loss of heterogeneity
flow cytometry markers for CLL
will have one of either kappa or lambda light chains
will have CD5 and CD23 cell markers
stage 0 of CLL
lymphocytosis…15 yrs
stage 1 of CLL
lymphocytosis and lymphadenopathy…8 yrs
stage 2 of CLL
lymphocytosis and splenomegaly…6 yrs
stage 3 of CLL
lymphocytosis and anemia…3 yrs
stage 4 of CLL
lymphocytosis and thrombocytopenia…2 yrs
what is treatment for CLL?
it is not a treatable disease…not curable and if you do treat it is seen to have same outcome as no treatment so dont give the patient toxic drugs for no effect
AML
acute myeloid leukemia
AML cell with issue
committed myeloid progenitor cell
what happens with myeloid development in AML ?
they myeloid cells lose ability to differentiate so you get a homogeneous mixture of myeloblasts
what percent blasts do you need for AML classification?
20% in blood or bone marrow
Auer rods
little rod like things seen in myeloblast…MEAN YOU HAVE AML
clinical manifestations of AML with blood counts (3)
sever anemia, thrombocytopenia and neutropenia
Hyperleukocytosis in AML
leads to infiltrates on X ray in lung and mental state changes, due to blood stasis
how to get AML?
can be from MDS or MPD…can be from genetic mutations
treatment related…radiation therapy causes it
what is the common good cytogenetic abnormality in AML and common bad one in AML??
t(15;17) (PML/RARa)…acute promyelocytic leukemia is good
deletion of chromosome 5 and 7 is bad
is AML from MDS or MPD good or bad prognosis?
bad
is treatment caused AML good or bad prognosis?
bad
induction treatment for AML
7+3
7 days o pyrimidine analog (cytarabine)
3 days of anthracycline
this gives complete remission
consolidation treatment of AML, when and what drugs?
in younger adults where you want better than just remission…shooting for cure
high dosage of cytarabine for many cycles
if you have a high risk AML…what is something to consider if you get patient to remission?
allogenic stem cell transplant
treatment for APL
induction chemo from AML…plus all trans retinoic acid
what does all trans retinoic acid do for APL?
it releases the block on cell differentiation…allowing myeloid cells to differentiate again
FLT3 mutation in AML with normal cytogenetic
is a tyrosine kinase…leads to bad prognosis…in lots of de novo AML
ALL
acute lymphoblastic leukemia
ALL cell type affected
the committed lymphoid progenitor cell (pre T or B)
ALL cell differentiation?
ability to differentiate is lost so you get a population of lymphoblasts accumulating
Which of the luekemias is the kid cancer?
ALL
3 risk factors for ALL
familial syndromes like downs
prior radiation
prior chemo
how does ALL present on blood count?
usually leukocytosis with increased blasts in the blood
aleukemic in ALL?
when marrow is packed and not circulating the lymphocyte blasts into the blood
B cell ALL
better prognosis than T cell…in kids mainly
T cell ALL
presents in teenage years with mediastinal mass or soft tissue mass
much higher risk than B ALL
5 clinical presentations of ALL
anemia, neutropenia, thrombocytopenia, hepatosplenomegaly, tumor lysis syndrome
tumor lysis syndrome
manifestation of high cell turnover leading to hyperuricemia, hyperkalemia hypocalcemia, high LDH
can lead to uric acid in kidneys and renal failure
are lymph nodes invoved in ALL ?
yes, more than in AML
two common places for ALL to get involved
CNS and testicular in males, must prevent CNS relapse with therapy
prognosis based on age in ALL
if you are less than 1 it is bad, and if you are more than 10 it is bad ( T cell)
what white cell count signals bad prognosis in ALL?
greater than 50x10^9
what is the genetic change with bad prognosis in ALL
t(9;22) same as CML, hypodiploidy
what is the genetic change with good prognosis in ALL
t(12;21) and hyperdiploidy
cell markers for ALL
CD19 CD10 no surface light chain
TdT
What is TdT and why is it a marker for ALL?
it is an early marker for lymphocytes so since ALL arrests the lymphoblasts you get these markers present
