Leukemias

Question 1

Acute leukemias

Answer 1

more than 20% blasts in bone marrow or peripheral blood, they crowd out normal hematopoiesis

Question 2

Acute myeloid leukemia (AML)

Answer 2

neoplastic accumulation of myeloid blasts; most common in older adults (65 yrs)

Question 3

AML causes

Answer 3

Congenital (Down’s syndrome less than 5 yrs old (M7), Bloom’s syndrome, Fanconi’s anemia), acquired (myelodysplastic syndrome, myeloproliferative disorders), environmental factors

Question 4

AML diagnosis

Answer 4

Peripheral smear shows Auer Rod (aggregation of myeloperoxidase), myeloid blasts; Flow cytometry: MPO, CD13, CD33, CD117, CD15, CD64, CD14

Question 5

AML cytogenetics

Answer 5

Favorable: t(15;17), t(8;21), inv (16); standard +8, +21

Question 6

M3 type of AML

Answer 6

(10% of AML), 85-90% curable; presented with DIC; t(15;17); generates fusion protein PML/RAR that causes maturation arrest in promyeloycte stage; treat with ATRA (all trans retinoic acid), degrades fusion protein to stop transcriptional repression and allow maturation, used along with chemotherapy

Question 7

AML treatment

Answer 7

induction (7 days cytarabine + 3 days anthracycline) then consolidation (cytarabine for younger, cytarabine + anthracylcline for older)

Question 8

Acute lymphoblastic leukemia (ALL)

Answer 8

neoplastic accumulation of lymphoid blasts; most common in children (10 yrs); associated with Down Syndrome over 5 years old

Question 9

B cell ALL markers

Answer 9

(80% of ALL); Tdt, CD10, CD19, CD20, CD22, cyto Ig

Question 10

T cell ALL diagnosis/markers

Answer 10

(20% of ALL); Tdt, CD1 to CD8; thymic (mediastinal) mass in young adults

Question 11

ALL cytogenetics

Answer 11

t(9;22) is Philadelphia chromosome = bad prognosis (20-25% in adults, 2-4% children); t(12;21) = better prognosis (2-3% adults; 20-25% children)

Question 12

Chronic lymphocytic leukemia (CLL)

Answer 12

neoplastic accumulation of mature B cells; most common adult leukemia (median affected 60 yrs); usually asymptomatic, progresses slowly

Question 13

CLL diagnosis

Answer 13

smudge cells (broken down nucleus of CLL cells), CD5+, CD20+

Question 14

Chronic myeloid leukemia (CML)

Answer 14

neoplastic accumulation of mature myeloid cell especially granulocytes; median diagnosis age 64 years

Question 15

CML diagnosis

Answer 15

basophilia, absence of LAP, t(9;22) Philadelphia chromosome

Question 16

CML treatment

Answer 16

Imatinib (tyrosine kinase inhibitor), oral drug, manageable side effects, prolonged and durable remission in about 90% patients, few patients now need stem cell transplant

Question 17

Polycythemia vera

Answer 17

neoplastic accumulation of mature myeloid cells, predominately RBCs; high RBC count, high Hb, EPO low, Jak 2 mutation

Question 18

Essential thrombocytosis

Answer 18

increased and enlarged megakaryocytes, increased production of platelets, Jak 2 mutation (50%), median age 60 -> risk of thrombosis

Question 19

Myelofibrosis

Answer 19

Characterized by bone marrow fibrosis (proliferation of fibroblasts) and extramedullary hematopoiesis -> teardrop RBCs, splenomegaly

Question 20

Myelodysplastic syndrome

Answer 20

stem cell disorders causing ineffective hematopoiesis, BM hypercellular, increase in myeloid blasts but less than 20%, peripheral blood cytopenias, can progress to AML; Pelger-Huet anomaly after chemotherapy

Question 21

Autologous stem cell transplant

Answer 21

Possible tumor content, no GVHD/ GVL, 0-10% treatment related mortality

Question 22

Allogeneic stem cell transplant

Answer 22

Need HLA matching and donor, no tumor content, high rate of GVHD/ GVL, 20-40% treatment related mortaility

Question 23

Graft verus host disease (GVHD)

Answer 23

graft T cells recognize host tissues as foreign