14 - Myelodysplastic Syndromes and Acute Leukemias Flashcards by Karen Marsden

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

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most common clonal hematologic disorder

myelodysplastic syndrome

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age/gender more likely to get MDS

men, old (increases logarithmically with age)

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typical type of mutation causing MDS

chromosomal deletions or additions, often chromosomes 5 or 7

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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

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clinical manifestations of MDS

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

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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

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isolated del(5q)

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

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supportive care for MDS

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

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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

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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

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who gets more AML - adults or children

adults

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risk factors for AML

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

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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)

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t(8,21) is assoc w/

AML w/ maturation (M2)

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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?

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