14 - Myelodysplastic Syndromes and Acute Leukemias

Question 1

myelodysplastic syndrome definition

Answer 1

spectrum of clonal myeloid disorders characterized by:
ineffective hematopoiesis
cytopenias
qualitative disorders of blood cells
clonal chromosomal abnormalities
variable tendency to evolve into acute leukemia

Question 2

most common clonal hematologic disorder

Answer 2

myelodysplastic syndrome

Question 3

age/gender more likely to get MDS

Answer 3

men, old (increases logarithmically with age)

Question 4

typical type of mutation causing MDS

Answer 4

chromosomal deletions or additions, often chromosomes 5 or 7

Question 5

risk factors for MDS

Answer 5

radiation
drugs/toxins - benzene, alkylating agents, topoisomerase 2 inhibitorss, smoking, hair dye, pesticides etc
other hematologic disorders - aplastic anemia, PNH, congential neutropenia
genetic disorders - Downs, fanconi, NF

Question 6

clinical manifestations of MDS

Answer 6

anemia sx, thrombocytopenia (bleeding/bruising), leukopenia (infxns), polyarthritis, neuropathy, splenomegaly, acquired alpha thalassemia

Question 7

PBS findings in MDS

Answer 7

RBCs - anisocytosis, normo-mildly macrocytic, low retics, Howell Jolly bodies, Cabot rings, basophilic stipling
WBCs - small poorly granulated neutrophils w/ hyper or hypo lobed nuclei
platelets - large and agranular

Question 8

isolated del(5q)

Answer 8

MDS
primarily in middle aged women
macrocytic anemia and normal/inc platelets
megakaryocytes have hypolobulated nuclei
favorable clinical course

Question 9

supportive care for MDS

Answer 9

EPO, G-CSF, GM-CSF, IL-11, transfusions, iron chelation, pyridoxine, folic acid, danazol
immunomodulation - cyclosporine, steroids
AML style chemo

Question 10

5-azacytidine (vidaza) and decitabine (dacogen)

Answer 10

vidaza is prodrug version of dacogen
reduces DNA methylation > allows reactivation of silenced tumor suppressors
significant side effects - cytopenias, GI, fever, fatigue, aches/pains

Question 11

general characteristics of acute leukemias

Answer 11

clonal - originate from transformed hematopoietic stem cell
malignant cells do not differentiate or do so abnormally > accumulate in blood, marrow, tissues
inhibits normal hematopoiesis
fatal if untreated

Question 12

who gets more AML - adults or children

Answer 12

adults

Question 13

risk factors for AML

Answer 13

genetic - Downs, klinefelter, fanconi, Bloom’s
prior chemo - alkylating agents and topoisomerase II inhibs
radiation
benzene
myelodysplasia, MPDs

Question 14

important translocations assoc w/ AML

Answer 14

t(8,21) - AML w/ maturation (M2)
t(15,17) - acute promyelocytic leukemia (M3)
inv(16) - acute myelomonocytic leukemia (M4)

Question 15

t(8,21) is assoc w/

Answer 15

AML w/ maturation (M2)

Question 16

t(15,17) is assoc w/

Answer 16

acute promyelocytic leukemia (M3)

Question 17

inv(16) is assoc w/

Answer 17

acute myelomonocytic leukemia (M4)

Question 18

clinical presentation of AML

Answer 18

cytopenias
hyperleukocytosis (inc risk of CNS involvement)
extramedullary dz (gums in M4/5, chloromas w/ M2, CNS)
coagulopathy

Question 19

gum infiltration can be seen with

Answer 19

AML (M5)

Question 20

prognosis (general good/bad/ugly) for AMLs M2, M3, M4

Answer 20

all good

Question 21

M3 AML

Answer 21

acute promyelocytic, t(15,17)
seen in younger hispanic pts
risk of DIC relatively high
tx w/ all trans retinoic acid

Question 22

tx of AML

Answer 22

induction chemo - anthracycline + cytarabine
consolidation chemo
bone marrow transplant

Question 23

special tx for M3 AML

Answer 23

ATRA (all trans retinoic acid) + (chemo OR arsenic)

Question 24

prognosis for AML - remission vs long term cure for adults and children

Answer 24

adults - 70% remission, 30% cure

children - 90% remission, 40% cure

Question 25

ALL is more common in kids or adults?

Answer 25

kids

Question 26

risk factors for ALL

Answer 26

in utero events, radiation, SES (higher > higher risk), ethnicity (hispanic)

Question 27

ALL is more often B or T cells?

Answer 27

B

Question 28

presentation of ALL

Answer 28

fatigue, malaise, arthralgia, bone pain, lymphadenopathy, hepatosplenomegaly, fever/infxn, bleeding, CN/neuro abnormalities

Question 29

good prognostic factors for ALL

Answer 29

female, age 3-8, low WBC, Pre-B phenotype, C10, low LDH, hyperdiploid cytogeneitcs

Question 30

tx of ALL

Answer 30

one drug is NEVER enough (most drugs are active against it)
tx for at least 18 mo
get sanctuary sites (CNS)
more risk > more intense tx
early response is very important prognostic factor
relapse is bad sign

induction chemo, consolidation chemo, re-induction, maintenance w/ POMP, BM transplant

Question 31

Burkitt lymphoma assoc genetic mutations

Answer 31

in the c-myc gene -
t(2;8)
t(8;14)
t(8;22)

Question 32

mutations in c-myc gene assoc w/

Answer 32

burkitt lymphoma

Question 33

tumor lysis syndrome and prevention

Answer 33

renal failure due to urate nephropathy and CaPO4 crystals

can be prevented w/ hydration, allopurinol, alkalinization, recombinant uricase

Question 34

are CNS findings more common in ALL or AML

Answer 34

ALL