14 - Myelodysplastic Syndromes and Acute Leukemias Flashcards
myelodysplastic syndrome definition
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
most common clonal hematologic disorder
myelodysplastic syndrome
age/gender more likely to get MDS
men, old (increases logarithmically with age)
typical type of mutation causing MDS
chromosomal deletions or additions, often chromosomes 5 or 7
risk factors for MDS
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
clinical manifestations of MDS
anemia sx, thrombocytopenia (bleeding/bruising), leukopenia (infxns), polyarthritis, neuropathy, splenomegaly, acquired alpha thalassemia
PBS findings in MDS
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
isolated del(5q)
MDS primarily in middle aged women macrocytic anemia and normal/inc platelets megakaryocytes have hypolobulated nuclei favorable clinical course
supportive care for MDS
EPO, G-CSF, GM-CSF, IL-11, transfusions, iron chelation, pyridoxine, folic acid, danazol
immunomodulation - cyclosporine, steroids
AML style chemo
5-azacytidine (vidaza) and decitabine (dacogen)
vidaza is prodrug version of dacogen
reduces DNA methylation > allows reactivation of silenced tumor suppressors
significant side effects - cytopenias, GI, fever, fatigue, aches/pains
general characteristics of acute leukemias
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
who gets more AML - adults or children
adults
risk factors for AML
genetic - Downs, klinefelter, fanconi, Bloom’s
prior chemo - alkylating agents and topoisomerase II inhibs
radiation
benzene
myelodysplasia, MPDs
important translocations assoc w/ AML
t(8,21) - AML w/ maturation (M2)
t(15,17) - acute promyelocytic leukemia (M3)
inv(16) - acute myelomonocytic leukemia (M4)
t(8,21) is assoc w/
AML w/ maturation (M2)
t(15,17) is assoc w/
acute promyelocytic leukemia (M3)
inv(16) is assoc w/
acute myelomonocytic leukemia (M4)
clinical presentation of AML
cytopenias
hyperleukocytosis (inc risk of CNS involvement)
extramedullary dz (gums in M4/5, chloromas w/ M2, CNS)
coagulopathy
gum infiltration can be seen with
AML (M5)
prognosis (general good/bad/ugly) for AMLs M2, M3, M4
all good
M3 AML
acute promyelocytic, t(15,17)
seen in younger hispanic pts
risk of DIC relatively high
tx w/ all trans retinoic acid
tx of AML
induction chemo - anthracycline + cytarabine
consolidation chemo
bone marrow transplant
special tx for M3 AML
ATRA (all trans retinoic acid) + (chemo OR arsenic)
prognosis for AML - remission vs long term cure for adults and children
adults - 70% remission, 30% cure
children - 90% remission, 40% cure
ALL is more common in kids or adults?
kids
risk factors for ALL
in utero events, radiation, SES (higher > higher risk), ethnicity (hispanic)
ALL is more often B or T cells?
B
presentation of ALL
fatigue, malaise, arthralgia, bone pain, lymphadenopathy, hepatosplenomegaly, fever/infxn, bleeding, CN/neuro abnormalities
good prognostic factors for ALL
female, age 3-8, low WBC, Pre-B phenotype, C10, low LDH, hyperdiploid cytogeneitcs
tx of ALL
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
Burkitt lymphoma assoc genetic mutations
in the c-myc gene -
t(2;8)
t(8;14)
t(8;22)
mutations in c-myc gene assoc w/
burkitt lymphoma
tumor lysis syndrome and prevention
renal failure due to urate nephropathy and CaPO4 crystals
can be prevented w/ hydration, allopurinol, alkalinization, recombinant uricase
are CNS findings more common in ALL or AML
ALL
