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)