CML Myeloproliferative disorders

Question 1

stages of CML

Answer 1

has three phases:

chronic stable phase,

accelerated phase

blast crisis

Question 2

clinical presentation of chronic stable phase (85% of pts at the time of diagnosis) of CML

Answer 2

asymptomatic non specific systemic symptoms of fatigue, weight loss and malaise abdominal pain (usually to splenomegaly) anemia, leukocytosis, thrombocytosis <10% blast in bone marrow and periphery

Question 3

clinical presentation of accelerated phase of CML

Answer 3

progressively worsening leukocytosis 10-20% of blasts cells on bone marrow biopsy or periphery

Question 4

blast crisis clinical presentation of CML

Answer 4

>30% blasts in bone marrow or >20% blasts in periphery resembles acute leukemia extramedullary blast infiltrates (sarcoma) possibly may see sudden increase in hepatosplenomegaly.

Question 5

what do we see on labs with CML?

Answer 5

anemia, thrombocytosis, and leukocytosis and bone marrow is hypercellular

Question 6

diagnosis of CML is confirmed via

Answer 6

identifying the philiadelphia chromosome with BCR-ABL1 fusion gene or the BCR-ABL1 fusion mRNA.

Question 7

how to we treat CML in blast crisis?

Answer 7

tyrosine kinase inhibitors or (imatinib as first line therapy)

may get a bone marrow transplant depending on response to medication and existing comorbidities.

Question 8

Who gets CML?

Answer 8

older men

Question 9

symptoms of CML

Answer 9

asymptomatic or non specific symptoms B cell (Fatigue, night sweats, weight loss) hepatosplenomegaly and peripheral eosinophilia or basophilia

Question 10

what is the clonal hematological malignancy change of CML?

Answer 10

see translocation of 9 and 22 (philiadelphia chromosome) appears in adults around 67 yrs and is about 15% of all adult leukemias

Question 11

vague abdominal pain with fatigue, hepatosplenomegaly and see leukocytosis with basophilia (>200 cell/ul) what does this person have?

Answer 11

CML - this is a myeloproliferative disorder that causes 15-20% of all leukemias

Question 12

What must always be checked in a suspected CML pt?

Answer 12

check for reciprocal translocation of ABL1 gene between chromosome 9 and 22 (seen in 90-95% of all pts). Can check this on peripheral blood

Question 13

peripheral eosinophilia, basophilia and thrombocytosis is seen with

Answer 13

CML

Question 14

what must be ruled out for CML?

Answer 14

need to make sure it’s not a leukemoid reaction

Leukomoid reaction - s_ee elevation of WBC with neutrophil count with left shift and increased band forms or metamyelocytes from infectious causes_. seen in acutely ill patients like in C diff.

need chromosomal evaluation to distinguish if clinical history doesn’t distinguish.

Question 15

Treatment of CML is with

Answer 15

therapy is required at diagnosis to all CML pts and to prevent progression to blast phase and subsequent AML

Treat with tyrosine kinase inhibitors - treatment of choice with chronic phase CML.

Three tyrosine kinase inhibitors are:

imatinimib

dasatinib

nilotinib

Question 16

Examples of tyrosine kinase inhibitors are:

Answer 16

Three tyrosine kinase inhibitors are:

imatinimib

dasatinib

nilotinib

They bind to BCR-ABL oncoprotein and prevent downstream signaling.

This has improved survival with CML and reduced the need for stem cell transplants.

Question 17

Treatment of accelerated CML or blast phase CML need to treat with

Answer 17

allogenic hematopoietic stem cell transplant.

Question 18

Contraindications to Tyrosine kinase inhibitors are:

Answer 18

pregnancy

Question 19

side effects of tyrosine kinase inhibitors:

Answer 19

cause fluid retention

prolong QT

have drug drug interactions

Question 20

Treatment of refractory CML?

Answer 20

Novel TKI’s are for refractory CML - bosutinib and ponatinib