Chronic Granulocytic Leukaemia - Myeloproliferative Disorders (MPD)

Chronic Granulocytic Leukaemia

·        = Chronic Myeloid Leukaemia

·        Clinical presentation

o   Any age

o   Tired, off colour, sweats

o   Slow onset

o   Large spleen (also liver)

·        Lab results: 

o   ­­WBCs (30 – 300). In chronic there will be mature and immature blasts (myelocytes, promyelocytes and lymphocytes as well. Just a general left shift). In acute there will be immature only. 

o   Bone marrow has ­­neutrophils

o   Philadelphia chromosome +ive

o   Low leukocyte alkaline phosphatase (LAP)

o   ­Uric acids

·        Course:

o  Chronic phase: median duration 3 – 4 years

o  Transformation (either to myeloblastic/AML or lymphoblastic) aggressive/acute – end stage

·        Treatment:

o  Hydroxyurea: controls proliferation but won‟t stop transformation

o  Interferon: suppresses marrow, in 15% Philadelphia goes away (® no transformation)

o  Autotransplant: use patient‟s stem cells

o  Allotransplant (use sibling): 60% cure, 20% death, 20% remission

o  MUD (Matched unrelated donor) 

o  „Mini-transplant‟: new stem cell technique with no high dose chemo/radiotherapy. Transplant mops up weakened immune system without you needing to kill it

o  New drug: Glevac (STI571) – targets Philadelphia Chromosome:

§  Acquired genetic defect – 9:22 translocation ® BCR-ABL oncogene (functional oncogene) ® P210-BCR-ABL oncoprotein

§  Leads to cell proliferation, ¯adhesions and ¯apoptosis without regulation