Haem Flashcards
what is leukaemia + how does it present
leukaemia = uncontrolled proliferation of primitive/stem cells in bone marrow
causes bone marrow failure so:
fatigue/SOBOE = anaemia
bleeding = thrombocytopenia
infections common = neutropenia
what are the types of leukaemia
myeloid = myeloid precursors affected, neutrophils
lymphocytic = lymphoid precursors affected, B cells
acute = immature cells - malignant precursors, as cell differentiation impaired
chronic = mature cells, as cell differentiation normal but excessive proliferation of malignant mature cells
ALL = most common cancer in children
CLL
CML = philadelphia chr 9:22 (BCR-ABL)
AML = poor prognosis if DNMT3A gene present, good risk if CEBPA gene present
what gives good + poor risk/prognosis for AML
good = CEBPA gene present, myeloid transcription factor
poor = DNMT3A gene present, DNA methyl transferase gene
what is Philadelphia chr
gene mutation in CML
translocation of long arms of Chr9 + Chr22
BRC-ABL oncoprotein forms, increases tyrosine kinase activity
FISH identifies t(9:22)
PCR identifies BRC-ABL
what identifies t(9:22) + BCR-ABL
FISH identifies t(9:22)
PCR identifies BRC-ABL
BCR-ABL = oncoprotein increasing tyrosine kinase activity
how do the different leukaemia present
ALL = children, painless lymphadenopathy, CNS palsy
CLL = B symptoms (weight loss, anorexia, night sweat)
CML = gout, B symptoms
AML = gum hypertrophy
ALL = most common cancer in children
CLL
CML = philadelphia chr 9:22 (BCR-ABL)
AML = poor prognosis if DNMT3A gene present, good risk if CEBPA gene present
how is leukaemia investigated
FBC, peripheral blood film
definitive diagnosis = biopsy
BM aspirate = morphology
BM trephine = histology to confirm diagnosis
what are blood film findings for leukaemia
ALL = leucocytosis, blast cells
CLL = smudge/smear cells
antibodies specific for CD5/19/20/23
CML = excess neutrophil/basophil (myeloid lineage)
FISH identifies t(9:22), PCR identifies BCR-ABL oncoprotein
AML = auer rod (red needle-like crystals containing peroxidase)
what determines prognosis + management of CLL
prognosis = IvGH mutation
management = p53 mutation or deletion
if p53 mutated/deleted (17p deletion):
1 - ibrutinib (bruton tyrosine kinase inhibitor)
2 - venetoclax if not tolerated
if p53 wild type:
FCR chemotherapy - fludranib, cyclophosphamide, rituximab (anti-CD20)
if complicated - due to ITP/AIHA (autoimmune haemolytic anaemia):
prednisolone
how are the leukaemia managed
ALL = chemotherapy
CLL = chemotherapy + watchful waiting (rising WCC + lymph nodes in 12months)
if 17p deletion (so p53 mutated/deleted) = ibrutinib (Bruton tyrosine kinase inhibitor)
if p53 wild type = FCR chemotherapy
if complicated by ITP/AIHA = prednisolone
CML = chemotherapy
1 - imatinib (tyrosine kinase inhibitor) + 3monthly PCR to monitor BCR-ABL
to reduce WCC = hydroxyurea/hydroxycarbamide
allogenic bone marrow transplant
AML = chemotherapy or bone marrow transplant
for fever, broad spectrum antibiotics (tazocin - piperralicin/tazobactam)
what is allogenic transplant
donated from another person
to reduce risk of graft vs host disease (as donor + host mismatches in HLA minor/major loci):
T cell depletion in donor + immunosuppressive host with cyclosporin
with chemotherapy, what is given
supportive antibiotic/antifungal therapy to prevent opportunistic infections
neutropenic sepsis due to pseudomonas bacteria (gram -ve) = tazocin (piperralicin/tazobactam) +/- gentamicin
coag -ve staph, staph aureus, strep pneumonia, group A strep
pneumocystis pneumonia due to PJP fungus from HIV
what is APML + how is it treated
APML = acute form of AML
translocation of Chr15 + Chr17 t(15:17), mutating RAR receptor that depends on retinoid acid
definitive diagnosis = PCR showing PML-RARA protein + FISH showing t(15:17)
treat with ATRA - all-trans retinoid acid (acid form of VitA)
what is myeloma
plasma cell dyscrasia (abnormal/disordered state)
so abnormal proliferation of post-germinal B cells = plasma cells (B cells that make monoclonal antibodies)
so myeloma causes excess amounts of that type of antibody to be made + its fragments secreted into serum/urine
also relative deficiency in functional antibodies, causing relative hypogammaglobulinaemia
what is multiple myeloma + MGUS
multiple myeloma = myeloma affects many areas of body
MGUS (monoclonal gammopathy of undetermined significance) = excess of 1 type of antibody, but no CRAB features present so not myeloma
waldestorm macroglubinaemia - progression of MGUS to higher levels of IgM antibodies
what immunoglobulin is most common in myeloma
usually IgG
waldestorm macroglobulinaemia is excess IgM instead
what are CRAB features of myeloma
at least 1 feature present for myeloma diagnosis:
hyperCalcaemia
Renal impairment
Anaemia
Bone pathology - more osteoclast activity, suppressed osteoblast so osteolytic lesions occur causing pathological + vertebral compression fractures
also plasma hyperviscosisty as too many immunoglobulins
so bruise/bleed easily, purple
why does hypogammaglobulinaemia occur if excess antibody made in myeloma
there is relative deficiency in functional antibody
what is antibody in myeloma called + what is protein in urine called
antibody referred to as monoclonal paraprotein
in urine, bence jones proteins found (contains light chains of antibody)
how is myeloma investigated
FBC - anaemia, hyperCa
CT/MRI for osteolytic lesion
high Cr/CRP/LDH = poor prognosis
serum protein electrophoresis - monoclonal paraprotein spike
urine bence-jones protein test - high amount of free light chains
definitive = bone marrow aspirate/biopsy, shows >10% plasma cells in bone marrow
how is multiple myeloma managed
if young pt with few comorbidities = haematopoetic stem cell transplant
1st line - chemotherapy = bortezomid, thalidomide, dexamethasone
manage myeloma bone disease:
bisphosphonate to suppress osteoclast
radiotherapy, surgery
