malignancies Flashcards
acute leukemia
Onset
Cell Type
Survival
Treatment
Rapid
Immature
Fatal if untreated
Aggressive chemotherapy
chronic leukemia
Onset
Cell Type
Survival
Treatment
Gradual
More mature
Long survival
Observation, chemotherapy or targeted agents
CM and PE of AML
67 yo
week history of fatigue as well as shortness of breath with exertion, low grade fever.
Physical exam shows gingival hyperplasia, petechiae over her arms.
splenomegaly
CNS-HA confusion TIA
PULM: respiratory distress
MC Acute form of leukemia in adults (80% of cases].
AML
AML labs
Profound anemia, thrombocytopenia
neutropenia
WBC>100,000
DX of AML
BONE MARROW
&>20% blasts.*
favorable or unfavorable dx for determination of need of stem cell transplant
Two types of AML
iv. Primary AML: arises de novo (new)
v. Secondary AML: Leukemia that develop from previous hematologic disorders or from previous chemotherapy for other cancers
tx of AML
Supportive care w/ transfusions
Chemotherapy - induction chemotherapy followed by consolidation chemotherapy
ATRA/Arsenic for AML-M3 subtype (causes DIC, bleeding complications)
Stem cell transplant
MC form of acute leukemia in children
Acute lymphoblastic leukemia
representing 80% of acute leukemia in children and 20% in adults
Highest incidence is 3-7 years
second rise around 40
CM of acute lymphoblastic leukemia seen as a result of bone marrow failure
Profound anemia (pallor, lethargy, dyspnea)
Neutropenia (FEVER MC SX, malaise, infxns of mouth, throat)
Thrombocytopenia (bruising, bleeding gums)
other than sxs of bone marrow failure what else do we see associated with CM of acute lymphoblastic leukemia
organi filtration
o Tender bones, LAD, splenomegaly, hepatomegaly in 20% of pts
o CNS involvement in 6%
headache, stiff neck, visual changes, vomiting. CNS & testes MC site for METS.
Work up for acute lymphoblastic anemia
Work up
Decreased or increased WBC
Peripheral blast
Elevated LDH, uric acid
Bone marrow blast present
Lumbar puncture
CXR may have enlarged mediastinal mass
CXR may have enlarged mediastinal mass
what is acute lymphocytic leukemia
Malignancy of lymphoid stem cells/BLASTS in bone marrow <=>lymph nodes, spleen, liver, other organs.
can be B cells T cells or non B/T
Pancytopenia seen with leukemia is the result of
crowding out from hyperproliferation of blasts
loss of RBC= anemia
loss of platelets= thombocytopenia and purpura
neutropenia= infx and fever
spilling of blasts = increase in WBC
differentiating blasts on a smear
they are huge and have low cytoplasm
How do you differentiate ALL from AML
How do you differentiate ALL from AML
TDT
Terminal deoxynucleotidyl transferase = ALL
“ ↑ LDH & uric acid
“ Peripheral blast
“ CXR – may have mediastinal mass
myeloperxidase or aeur rod
most common subtype of ALL
BALL
C10
C19
C20
would you see CNS directed tx for ALL or AML
ALL
this is to prevent and treat CNS dz
genetically modified T cells
Allogeneic transplant
Allogeneic transplant Imatinib
indicated for
philadephia chromosome positive ALL, primary refractory or early relapsed dz
with this chronic leukemia you have cells dividing too quickly
cml
both result in cytopenia
With this chronic leukemia you have cells not dying when they should be
CLL
both result in cytopenia
CML most common cause
translocation of philadelphia
T 9;22
BCR-ABL Oncogene
- Stem cell disorder
- Characterized bymyeloproliferation
- Well-described clinical course
22 is philadelphia
forces continual divisions or premature leukocytes
causes spill over into the blood
splenomegaly
can progress and accelerate in blast crisis
Dx hallmark of CML
= leukocytosis w/ WBC 50K
CM
Male to female ratio 1.4 to 1
Most frequently b/w ages 40 to 60, but may occur at any age
Symptoms related to hypermetabolism: (weight loss, anorexia, night sweats)
Splenomegaly is often present
Anemia
Bruising, epistaxis from platelet dysfunction
BCR-ABL causes CML how
turns on tyrosine kinases and leads to build up of premature leukocytes
more to liver and spleen causing swelling
lab dxs for CML
Lab work up
Increased WBC: usually >50K, usually see a complete spectrum of myeloid cells
Increased basophils
Normocytic anemia
Platelet may be increased, normal or decreased
Bone marrow is hypercellular
PH chromosome positive
tx of CML
” Tyrosine kinase inhibitors
“ Chemotherapy
“ Interferon
“ Stem cell transplant -
when would we use stem cell transplant for CML
in imatinib failure
how do you monitor for pt undergoing tx for CL
check CBC reguarly
6mo Bone marrow biopsy
then monitor every three moneths with peripheral blood PCR for BCR-Abl
MC type of CLL and when do we see it
B cell Chronic lymphocytic leukemia
iv. Peak incidence age 60 to 80
MC in western world
tx for CLL
Indolent disease, many patients never need chemotherapy
Treat if symptomatic: organomegaly, hemolysis, bone marrow suppression’
“ Chemotherapy (FCR Therapy - best frontline regimen
specific dx for CLL
isolated lymphocytosis w/ leukocytosis > 20K
Smudge cells
Uncommon B cell lymphoproliferative disorder With a higher prevalence in males
hairy cell leukemia
CM of hairy cell leukemia
Peak incidence 40-60 years
Clinical presentation: infections, anemia or splenomegaly
Lymphadenopathy is very UNCOMMON
Pancytopenia is usual
tx for Hairy cell
2 CDA or pentostatin
achieve response in >80% patients.
tx for non-hodkins
R-CHOP therapy = MC regimen
standard dx for lymphoma
biopsy of lymp nodes
non-hodkin’s lym,phoma dx
Excisional Lymph node biopsy
CBC, CMP, LDH, Uric acid, Serum protein electrophoresis
CT, CXR for staging
Bone marrow biopsy
most common non-hodgkin’s lymphoma
B cell lymphoma (lymph tumor) comprises 85% of cases
T cell and NK cell together comprises 15% of cases.
sxs of non-hodgkin’s
Lymphadenopathy: Asymmetric painless enlargement of lymph nodes
Constitutional symptoms: fever, night sweats, weight loss. Oropharyngeal involvement in 5-10%
Infections
with extra-nodal involvement:
BO, anemia, weakness (spinal cord)
reed-sternberg cell is associated with
non-hodgkin
describe non-hodkin lymphoma
genetic mutation leads to lymphomas
can be nodal or extra-nodal
if extranodal can cause GI (MC) BO
cause pancytopenia in the bone marrow
or spinal cord compression
MC form of NHL
indolent follicular lymphoma
mean survival is 10 years
NHL associated with elevated IgM
Lymphoplasmacytoid lymphoma
Second MC type of NHL
Diffuse large B cell lymphoma
this one is aggressive
- R-EPOCH
high risk NHL treatment that requires hospitalization
types of t cell NHL
Peripheral T cell lymphoma
Angiioimmunoblastic
lymphadenopathy
Mycosis fungoides- causes patches on the skin
Sezary syndrome
when would you use radiation tx for NHL
consider for stage DLBCL
sxs of HL
” Can present at any age: peak incidence in young adults
“ Mediastinal involvement in 6-11%
“ Constitutional symptoms can be prominent
types of HL
nodular sclerosis
mixed cellularity
lymphocyte depleted, lymphocyte rich
Nodular lymphocyte predominant
tx of HL
Treatment
“ Chemotherapy
“ Radiation
“ Both
Late effects of Hodgkin’s disease and treatment can include secondary lung cancer, myelodysplasia, cardiac disease.
Multiple myeloma
Neoplastic proliferation characterized by plasma cell accumulation in the bone marrow, the presence of monoclonal protein in the serum and or urine and related tissue damage.
B sxs with HL indicate
Systemic “B” symptoms (advanced disease)
(cytokines => Pel-Ebstein fever (cyclical fever
that increase & decrease over a period of 1-2 weeks, night sweats), weight loss, anemia, pruritus
CM on early HL
firm, non-tender, freely mobile(especially supra clavicular, cervical
&mediastinal)
.Alcohol may induce lymph node pain.*
Hepatosplenomegaly.
CD15+, CD30+.
“owl-eye appearance”
both characteristic of
HL
Cancer associated with proliferation of a single clone of plasma cells*
multiple myeloma
increase in monoclonal Ab Especially IgG or IgA
CM of multiple myeloma
Bone pain Recurrent infx Elevated Ca Anemia Kidney failure
only heme malignancy associated with bone destruction
multiple myeloma
dx of multiple myeloma
o CBC → anemia and reouleaux formation o Creatinine o ↑ Calcium o ****SPEP: monoclonal M protein spike UPEP --> 24 hr urine - Bence Jones Protein; Bone marrow biopsy
what bone changes might we see in a pt with multiple myeloma
Skull Radiographs: “punched-out”Ivtic lesions. * Bone scans NOT helpful!
tx of multiple myeloma
supportive
Autologous stem cell transplant definitive treatment.
tPreceded by chemotherapy ex.
Thalidomide or alkylating agents ex. Melphalan).
Bisphosphonates for bony destruction.
Myeloproliferative disorder
Bone marrow disorder characterized by clonal proliferation of one or more hematopoietic components in the bone marrow.
three types of myeloproliferative disorder
- Polycythemia Vera
- Essential thrombocynthemia
- myelofibrosis
Polycythemia Vera
primarily seen as the increase in RBC
but also seen as increase in WBC and platelets
Polycythemia sxs
Headache, pruritus, facial plethora, splenomegaly, HTN. Gout can be a result of elevated uric acid.
pruritus associated with hot bath
tx of polycythemia
Phlebotomy to maintain hct <45
Hydrea can be used for patients who cannot tolerate phlebotomy, or has progressive splenomegaly, thrombocytosis.
Interferon is another option. It is less convenient than oral hydrea.
Median survival 10-16 years. Transition to myelofibrosis occurs in 30% pts, about 5% progresses to leukemia.
hallmark of essential Thrombocynthemia
Sustained increase in platelet count
what labs do we see with Thrombocynthemia
ii. Hematocrit is normal
iii. Half of patient has JAK-2 mutation
o JAK-2 mutation
o ↑ Megakaryocytes
complications of Thrombocynthemia
iv. Clinical complications: thrombosis and hemorrhage
erythormelagia, up to 40% has splenomegaly
polycythemia
Polycythemia
o JAK2 mutation
o ↓ EPO
increased Hct in the absence of hypoxia
sustained increase in platelet count is characteristic of this myeloproliferative disorder
essential thrombocytopenia
what would you expect to see in the bone marrow of a pt with essential thrombocytopenia
bone marrow shows increase megakaryocytes
excess production of RBCs is characteristics of which myeloproliferative
what age gorup do we normally see hthis in
polycythemia
50-60yr
median survival 10 years
clinical sxs of polycythemia
HA, pruritis
faical plethora
HTN
gout as a result of elevated uric acird
what would be the tx for a pt with myeloproliferative d/o
phlebotomoy to maintain <45 PO hdyrea can be used
thombocytosis indterferon alternative to hydrea
