leukaemia Flashcards
what is haematopoesis
marrow - myeloblast-promuelocyte-myelocyte-metamyelocyte-band neutrophil-neutrophil (blood to tissue) or myeloblast-promonocyte-monocyte(blood)-immaure macrophage-mature macrophage(tissue)
what is G-CSF
granulocyte colony stimulating factor promotes neutrophils (main driving factor)
what growth factors affect white blood cells
bone marrow maturation - SCF, G-CSF, IL-3, GM-CSF
Allow tissue migration
what is cancer
transformed cell phenotype (uncontrolled proliferation, failure to undergo apoptosis)
genetic (mutations in oncogenes, tumour suppressor genes)
epigenetic (deregulated gene expression, aberrant DNA methylation)
what are types of mutations that occur
point (change AA seq) translocation partial chromosome deletion chromosomal duplication dan methylation or deacetylation of histones surpasses gene transcription
what is the clonal evolution of leukaemia
take a while to emerge as cancer undergoes clonal selection to turn from normal to malignant clones
what are the clinical features of the 3 myeloproliferative disorders
polycythemia rubra vera
myelofibrosis
essential (massive splenomegaly) thrombocythemia
leucoerythroblastic blood film picture
what is the JAK-STAT signalling (pathway for EPO and G-CSF)
acquired mutation in JAK-2 gene transmitted to receptor so switched on to result in the 3 conditions
can all progress to acute myeloid leukaemia
what is the mutation in the JAK-2 gene
the same for all 3 JAK2 V617F (g to t)
what are treatments of MPDs
reduce spleen size
lower Hb, platelets and WBC counts
what is chronic myeloid leukaemia
too many white cells
Buffy coat expanded in blood sample
translocation philadelphia chromosome (9;22)
how is CML diagnosed
FISHing for CML
FLUORESCENT IN STIU HYBRIDISATION
Translocation event of 9;22
what other DNA mutations can contribute to CMLF
BCR-ABL oncogene
what is the major CML treatment
imatinib
targeted therapy to bind to BCR-ABL oncoprotein - normalises white cell count and improves CML survival (over 90% from 50% after 5 years)
what can CML occasionally do
transforms to AML
What is acute myeloid leukaemia
uncontrolled proliferation of primitive cells in bone marrow
causes failure - anaemia, infections, bleeding
blasts identified on blood film (mitosis, large nucleus)
what are the clinical features of AML
anaemia infections DIC Ulcers Infiltration bruising
how is AML diagnosed
bone marrow biopsy morphology immunophenotyping genetic cytogenetic molecular
how is AML treated
chemotherapy - kills rapidly dividing cells, combo regimes, myeloid-ablative cycles of treatment
how can AML be treatment by allogenic stem cell transplantation
allograft (full or reduced intensity)
slibling (1 in 4 chance of match)
matched unrelated donor
what are supportive measures for AML treatment
transfusions (RBCs, Ps, Cryo/FFP)
AB (prophylactic, broad spec)
Antifungals
what is the aim of chemo
drive cell count low enough for body’s immune system to deal with it
transfusions to deal with each cycle
age and genetics also play a role
what is allogeneic transplantation
new bone marrow (harvest stem cell from matched donor) infused into patient (conditioned by chemo so donor cells can take up residence)
also needs intensive support, immunosuppression and close monitoring
what can result from allogeneic transplantation
opportunistic infections
Fungal infections
pneumocystis pneumonia
what is neutropenic sepsis
ME Gram -ve bacteria most dangerous blood cultures and blind antibiotic therapy if fever (Tazocin, meropenem, add AF) iv fluids if hypotensive inotropic support on ITU
what is graft vs host disease
donor/host mismatches in major and minor HLA loci
rejection reactions - skin rash, diarrhoea, deranged liver function
acute GVH and chronic GVH post transplant
what is graft vs leukaemia
how stem cell transplant cures leukaemia
how can graft vs host disease be treated
T-cell depletion of infused donor cells (graft)
Immunosuppression of recipient (ciclosporin)
Donor lymphocyte infusions (DLI) post-Tx can treat relapse by augmenting GVL effect
what gene can also cause AML
DNMT3A methyltransferase
