Leukemia Flashcards
Risk factors of leukemia
Most important: non random chromosomal abnormalities , most commonly translocation
Acute vs chronic leukemia
Acute- onset is weeks to months >20% blast cells
Chronic- months to years <10% blast cells
Immunophenotyping
Lymphoblasts- + PAS, + TDT, - LAP, - esterase
Myeloblasts- - PAS, - TDT, +LAP, +esterase
Acute lymphoblastic leukemia
- predominantly in children under 15
- 85% pre B cell origin while pre T cell origin tend to present as lymphomas
- increased incidence with Down syndrome
- sanctuary site CNS and Testis
Acute lymphoblastic leukemia risks and prognosis
90% cure rate in children
1/3 of adults with disease survive
Worse prognosis : <2 years old or >100000/Ul
Most common hyperploidy
T(9,22)bcc/abl Philadelphia chromosome poor prognosis ( more in adult ALL than child)
Testing acute ALL
B cell- TDT+, cd19,cd10…late vs early B cell can be determined by Igm heavy chain
T cell- TDT+ ,cd5, late vs early determined by presence of cd3,cd4,or cd8
Chronic lymphoid leukemia
- most common leukemia in adults over 60
- difference btw ALL Is blood lymphocytosis
- smudge cells present- fragile leukemia cells
- chromosomal translocations rare
- autoimmune thrombocytopenia or hemolytic anemia
Prognosis of CLL
- variable and slow progressing but median 5 years
- polymphocytic transformation ( 15-30% patients ): worsening cytopenia, increasing splenomegaly
- richter transformation(10% of patients) - diffuse large B cell lymphoma
- both transformations result in fatality within one year
Testing CLL
Cd19,cd20,cd5,cd23
Translocations rare
Immunoglobulin hypermutation commonly found- indicate less aggressive disease
Hairy cell leukemia
- rare, occurs more in men
- splenomegaly observed in almost all patients but lymphadenopathy rare
- pancytopenia
- prognosis good- indolent course….after one course of 2CDA 80% in complete remissions
Hair cell leukemia appearance and blood type
- hair like projections
- become meshed in ECM of marrow and prevent aspiration creating dry tap - ## cd19,cd20,cd11,cd103trap+- histochemical staining
Acute myeloid leukemia
- > 20% myeloid blasts
- most 40-60 year old
- aur rods especially with t(15,17) aka acute promyleocytic leukemia
- infiltration in gingiva by monocytes.
- 60% remission after chemo
T(15,17) best prognosis
AML with t (15,17)
- fusion change of RAR changes TF from activator to repressor
- fusion protein interferes with terminal differentiation of granulocytes
- can be overcome with treatment of all trans retinoic acid(tretinoin…natures leukemic cells to death) - may be associated with DIC (procoagulants in granules)
Myelodysplastic syndromes
- characterized by maturation defects associated w/ ineffective hematopoeisis
- high risk of transformation to AML, pancytopenia cells stay in marrow
- 70 year olds, survivor rate 9-29 months
- secondary to genotoxic therapy or radiation therapy - survival 4-8 months
myelodysplastic syndrome features
- increased risk of leukemia
- no hypercellular marrow unlike myeloproliferative
- spontaneous or drug related
- marrow aberrations including: refractory anemia, ringed sideroblasts, nuclear “budding”, excess blasts but less than 20%
- 25% develop into acute leukemia
Chronic Myelogenous leukemia
- hypercellular bone marrow
- low LAP, basophilia, and eosinophilia
- splenomagly
- PBS: leukocytosis, maturing granulocytic precursors, predominantly neutrophils…less than 10% blasts
- BCR-ABL gene aka Philly gene
CML clinical features
- 40-60 year old
- chronic phase avg 3 years min. symptoms
- 50% enter accelerated phase and 50% enter blast crisis w/out accelerated phase.
- Accelerated phase: inc : anemia, thrombocytopenia, basophilia. cytogenic abnormalities. acute leukemia w.in 6-12 months
- gleevac= inhibitor of tyrosine kinase produced by BCR-ABL
Polycythermia Vera
- associated with point mutation in tyrosine kinase JAK2
- No EPO required so levels are low
- oxygen saturation normal
- neoplasia of multipotent myeloid stem cells producing RBCs , granulocytes and platelets
Polycythermia vera symptoms
- inc total RBC mass= hyperviscosity and HTN
- poor oxygen delivery= headache, dizziness, vertigo, tinnitus
- stasis= DVT. stroke
- vascular distension nd platelet dysfunction=bleeding
- histamine release=pruritis
Labs-elevated RBC,hemoglobin,hematocrit,leukocytosis,thrombocytosis
polycythermia vera treatment
- -treatment-phlebotomy to maintain normal RBC mass-median survival 10 years
- EMH spleen and liver results in organomegaly
- w/out Rx death from bleeding or thrombosis within months of diagnosis
- 1/2% transform to AML
- 15-20% transform to spent pahse primary myelofibrosis
essential thrombocytosis
- disorder of multipotent progenitor cells
- assx w/ JAK2 or MPL activated by thrombopoetin
- inc platelet count
- inc. megakaryocyte size and number
- dysfunctional platelets- risk thrombosis and hemorrhage;12-15 yr survival
- erythromelagia-throbbing and burning of hands and feet
primary myelofibrosis
- disorder of multipotent progenitor cells
- activated JAK2 in 50-60% cases
- obliterative marrow fibrosis- dec bone marrow hematopoiesis-> cytopenia and EMH
- probably caused by inapropriate release of fibrogenic factors from megakaryocytes, PDGF and TGF beta
myelofibrosis w/myeloid metasplasia-
- deposition of collagen to marrow-> marrow failure
- teardrop RBC
- abnormally large platelets
- basophilia
- spent phase of disorders
- leukoerythroblastosis-nucleated RBC with immature WBC
