Leukemia

Question 1

Risk factors of leukemia

Answer 1

Most important: non random chromosomal abnormalities , most commonly translocation

Question 2

Acute vs chronic leukemia

Answer 2

Acute- onset is weeks to months >20% blast cells

Chronic- months to years <10% blast cells

Question 3

Immunophenotyping

Answer 3

Lymphoblasts- + PAS, + TDT, - LAP, - esterase

Myeloblasts- - PAS, - TDT, +LAP, +esterase

Question 4

Acute lymphoblastic leukemia

Answer 4

• 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

Question 5

Acute lymphoblastic leukemia risks and prognosis

Answer 5

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)

Question 6

Testing acute ALL

Answer 6

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

Question 7

Chronic lymphoid leukemia

Answer 7

• 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

Question 8

Prognosis of CLL

Answer 8

• 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

Question 9

Testing CLL

Answer 9

Cd19,cd20,cd5,cd23
Translocations rare
Immunoglobulin hypermutation commonly found- indicate less aggressive disease

Question 10

Hairy cell leukemia

Answer 10

• 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

Question 11

Hair cell leukemia appearance and blood type

Answer 11

• hair like projections
  - become meshed in ECM of marrow and prevent aspiration creating dry tap
• ## cd19,cd20,cd11,cd103trap+- histochemical staining

Question 12

Acute myeloid leukemia

Answer 12

• > 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

Question 13

AML with t (15,17)

Answer 13

• 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)

Question 14

Myelodysplastic syndromes

Answer 14

• 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

Question 15

myelodysplastic syndrome features

Answer 15

• 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

Question 16

Chronic Myelogenous leukemia

Answer 16

• 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

Question 17

CML clinical features

Answer 17

• 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

Question 18

Polycythermia Vera

Answer 18

• 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

Question 19

Polycythermia vera symptoms

Answer 19

• 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

Question 20

polycythermia vera treatment

Answer 20

• -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

Question 21

essential thrombocytosis

Answer 21

• 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

Question 22

primary myelofibrosis

Answer 22

• 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

Question 23

myelofibrosis w/myeloid metasplasia-

Answer 23

• deposition of collagen to marrow-> marrow failure
• teardrop RBC
• abnormally large platelets
• basophilia
• spent phase of disorders
• leukoerythroblastosis-nucleated RBC with immature WBC