CML

Question 1

Myeloproliferative disorders

Answer 1

Chronic myeloid leukaemia
Myelofibrosis
Polycythaemia

Question 2

What is Chronic myeloid leukaemia

Answer 2

Pluripotent stem cells dysregulation within bone marrow

Question 3

Who is CML most common in

Answer 3

> 60 yr olds

Question 4

Causes of CML

Answer 4

BCR-ABL fusion gene - 9-22 chromosome philadelphia translocation
Genetic susceptability
Environmental - radiation exposure
Lifestyle factors - smoking, obesity, alcohol consumption

Question 5

What is the genetic factors for CML

Answer 5

PHILADELPHIA CHROMOSOME = BCR-ABL fusion gene - reciprocal translation between long arms p chromosomes 9 and 22
BCR-ABL consistently active
Gene variants - SNPs in genes like IKZF1, ETV6 and MECOM

Question 6

How does BCR-ABL cause chronic myeloid leukaemia

Answer 6

mutated BCR-ABL tyrosine kinase -> BCR-ABL fusion protein drives uncontrolled cell growth and proliferation

Question 7

Symptoms of chronic phase CML

Answer 7

Fatigue/lethargy
Night sweats
Weight loss
Splenomegaly/infarction (pain)
Anaemia
Generalised lymphadenopathy
Hyperviscosity

Question 8

Features of splenomegaly

Answer 8

Bloating, early satiety, increased abdomen, N+V - exacerbate weight loss
CML -> massive splenomeagly, over 20cm

Question 9

What presentations can hyperviscosity cause with CML

Answer 9

Cerbrovascular event
Opthalmic complications secondarey to retinal vein occlusion

Question 10

First line investigations for CML

Answer 10

FBC
Blood fil
LDH
Bone arrow aspirate
Cytogenics

Question 11

FBC in CML

Answer 11

Leucocytosis - 20-60x109L
Thrombocytosis
Anaemia - normochromic and normocytic normally but can be hypo due to deficiencies

Question 12

Blood film in CML

Answer 12

Leucocytosis and leucoeruthroblastic in chronic phase - immature RBC/WCC in blood
accelerated - >15% blast cells high blast cells, promeylocytes and basophils high, marked TP
Blastic phase - >20% is blast cells

Question 13

Bone marrow infiltrate in CML

Answer 13

Hypercellular - increased myleoid cells - neutrophils, eosinophils and basophils and myeloid progenitors
Megakaryocytes seen
Fibrosis - reticulin stain

Question 14

Cytogenics in CML

Answer 14

Philadelphia translocation 90% patients
Double Ph-1 chromosome
Trisomy 8,9,19,21

Question 15

Chronic phase criteria CML

Answer 15

Asymptomatic
<10% blasts in peripheral blood or bone marrow aspirate
Years

Question 16

Accelerated phase CML criteria

Answer 16

10-19% in peripheral blood or bone marrow aspirate
>30% blood myeblasts and promyelocytes together
>20% basophils blood
Platelets <100
Thrombocytosis >1000 not responding to medical therapy
Rising leucocytosis and splenomegaly
Symptoms burden - anaeia, splenogmegaly etc

Question 17

Criteria for a blast phase/blast crisis CML

Answer 17

> 20% blastic leucocytes in peripheral blood
Evidence extramedullary blast production
Clusters blasts - bone marrow
Sev constitutional symtpoms and complications
Aggressive acute leukaemia - generally fatal

Question 18

Complications in blastic phaseCML

Answer 18

GI bleeding, infections immunocompormise and extrameduallry blastic clusters

Question 19

Progression CML

Answer 19

Chronic phase often lasts years
May progress over months from accelerated phase to blastic phase OR directly from chronic phase to blastic phase

Question 20

3 goals of treatment CML

Answer 20

Haematologic remission - normal FBC and physical exam
Cytogenic remission - no Ph+ cells
Molecualr remission - negative PCR for BCR/ABL mRNA mutated

Question 21

Treatment for CML

Answer 21

Tyrosine kinase inhibitor - imatibinib
May be considered for HSCT

Question 22

Second line CML

Answer 22

Second gen TKI - Nilotinib, dasastibib, bosutinib
3rd - ponatinib
If failure/intolerance imatinib

Question 23

Treatment for blastic phase

Answer 23

Imilonib + chemoterhapy prior to stem cell transplent

Question 24

CML complications

Answer 24

Sev anaemia
Infections - bone marrow failure - decreased humoral immuntiy
Thrombocytopenia - as disease or 2ndry to treatments
Hypervisocity

Question 25

Imatinib side effects

Answer 25

GI upset Kidney njury

Question 26

Prognosis CML

Answer 26

Near normal life expectancy if imatinib in choronic pahse if good response If not enduring response - 70% survival 3 years if imatinib in chronic phase Accelerated - 30%, blastic - 7% (v poor) HSCT - 50% survival

Question 27

Causes of thrombocytosis non malignant

Answer 27

Post surgery Infection/inflammation Bleeding Iron def Malignancy Rebound post chemo Hyposplenism/asplenia

Question 28

First line investigations thrombocytosis

Answer 28

Inflam markers eg CRP Ferritin Acute and clear - repeat when stimulus is over and check blood film if persistent

Question 29

When investigate thrombocytosis further

Answer 29

Persistent No seoncarry cause Splenomegaly UNprovoked thrombosiss

Question 30

Haematological causes of thrombocytosisi

Answer 30

Myeloproliferative neoplams - Essential thrombocytopenia T, PRV, MF, CL Any malgiancy

Question 31

IMatinib vs second gen TKIs

Answer 31

More potent but more side effects Evidence suggests no more effective long term Can swap between

Question 32

What monitor CML with

Answer 32

BCR-ABL1 fusion transcripts and FBC If suboptimal -> second gen TKI May stay off medication if good enough response

Question 33

What cells are high in each neoplasm myeloprolif

Answer 33

PCV - High RBC ET - high platelets CML - high WCC esp basophils MF - blood picture / but film changes and splenomegaly