CML Flashcards
Myeloproliferative disorders
Chronic myeloid leukaemia
Myelofibrosis
Polycythaemia
What is Chronic myeloid leukaemia
Pluripotent stem cells dysregulation within bone marrow
Who is CML most common in
> 60 yr olds
Causes of CML
BCR-ABL fusion gene - 9-22 chromosome philadelphia translocation
Genetic susceptability
Environmental - radiation exposure
Lifestyle factors - smoking, obesity, alcohol consumption
What is the genetic factors for CML
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
How does BCR-ABL cause chronic myeloid leukaemia
mutated BCR-ABL tyrosine kinase -> BCR-ABL fusion protein drives uncontrolled cell growth and proliferation
Symptoms of chronic phase CML
Fatigue/lethargy
Night sweats
Weight loss
Splenomegaly/infarction (pain)
Anaemia
Generalised lymphadenopathy
Hyperviscosity
Features of splenomegaly
Bloating, early satiety, increased abdomen, N+V - exacerbate weight loss
CML -> massive splenomeagly, over 20cm
What presentations can hyperviscosity cause with CML
Cerbrovascular event
Opthalmic complications secondarey to retinal vein occlusion
First line investigations for CML
FBC
Blood fil
LDH
Bone arrow aspirate
Cytogenics
FBC in CML
Leucocytosis - 20-60x109L
Thrombocytosis
Anaemia - normochromic and normocytic normally but can be hypo due to deficiencies
Blood film in CML
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
Bone marrow infiltrate in CML
Hypercellular - increased myleoid cells - neutrophils, eosinophils and basophils and myeloid progenitors
Megakaryocytes seen
Fibrosis - reticulin stain
Cytogenics in CML
Philadelphia translocation 90% patients
Double Ph-1 chromosome
Trisomy 8,9,19,21
Chronic phase criteria CML
Asymptomatic
<10% blasts in peripheral blood or bone marrow aspirate
Years
Accelerated phase CML criteria
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
Criteria for a blast phase/blast crisis CML
> 20% blastic leucocytes in peripheral blood
Evidence extramedullary blast production
Clusters blasts - bone marrow
Sev constitutional symtpoms and complications
Aggressive acute leukaemia - generally fatal
Complications in blastic phaseCML
GI bleeding, infections immunocompormise and extrameduallry blastic clusters
Progression CML
Chronic phase often lasts years
May progress over months from accelerated phase to blastic phase OR directly from chronic phase to blastic phase
3 goals of treatment CML
Haematologic remission - normal FBC and physical exam
Cytogenic remission - no Ph+ cells
Molecualr remission - negative PCR for BCR/ABL mRNA mutated
Treatment for CML
Tyrosine kinase inhibitor - imatibinib
May be considered for HSCT
Second line CML
Second gen TKI - Nilotinib, dasastibib, bosutinib
3rd - ponatinib
If failure/intolerance imatinib
Treatment for blastic phase
Imilonib + chemoterhapy prior to stem cell transplent
CML complications
Sev anaemia
Infections - bone marrow failure - decreased humoral immuntiy
Thrombocytopenia - as disease or 2ndry to treatments
Hypervisocity
Imatinib side effects
GI upset
Kidney njury
Prognosis CML
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
Causes of thrombocytosis non malignant
Post surgery
Infection/inflammation
Bleeding
Iron def
Malignancy
Rebound post chemo
Hyposplenism/asplenia
First line investigations thrombocytosis
Inflam markers eg CRP
Ferritin
Acute and clear - repeat when stimulus is over and check blood film if persistent
When investigate thrombocytosis further
Persistent
No seoncarry cause
Splenomegaly
UNprovoked thrombosiss
Haematological causes of thrombocytosisi
Myeloproliferative neoplams - Essential thrombocytopenia T, PRV, MF, CL
Any malgiancy
IMatinib vs second gen TKIs
More potent but more side effects
Evidence suggests no more effective long term
Can swap between
What monitor CML with
BCR-ABL1 fusion transcripts and FBC
If suboptimal -> second gen TKI
May stay off medication if good enough response
What cells are high in each neoplasm myeloprolif
PCV - High RBC
ET - high platelets
CML - high WCC esp basophils
MF - blood picture / but film changes and splenomegaly
