The Case Of The Worried Midwife + Samba-playing Grandmother Flashcards
Blood film reviewed by weekend on-call consultant: • Neutropenia • Marked thrombocytopenia • Primitive myeloid blast cells • Auer rods seen
Comment: morphology consistent with diagnosis of acute myeloid leukaemia – minimally differentiated blasts (FAB M1 subtype)
symptoms of AML
Fatigue, SOB (anemia)
Bleeding, bruising (thrombocytopenia)
Infection (neutropenia)
DIC
what do you seen on a blood film in AML?
primitive myeloid blast cells with Auer rods
Auer rods
cytoplasmic inclusion bodies seen in AML (especially the promyelocytic type)
how to diagnose AML?
how to diagnose AML
bone marrow biopsy
what analysis is done with the bone marrow biopsy? (AML)
immunophenotyping
genetic, chromosomal and molecular analysis
3 gene mutations common in AML
DNMT3A
FLT3
NPM1
what affects prognosis in AML?
age at diagnosis
presence of gene mutations
what gene mutations have a poor prognosis in AML?
p53 and FLT3 mutations
treatment for AML
DA 3+10 chemotherapy regime
supportive therapy
allogeneic stem cell transplantation
DA 3+10 regime
daunorubicin infusions on days 1, 3, 5
cytarabine infusions days 1-10
what is supportive therapy for chemo patients?
platelet and red cell transfusions
prophylactic broad spectrum Abx and anti-fungals
expected blood count after chemo?
pancytopenic for around 3 weeks
injection of what can help blood counts recover after chemo?
granulocyte colony stimulating factor (GCSF)
allogeneic transplantation
When a relative or unrelated person having a close HLA type is the donor.
medical emergency caused by chemotherapy
medical emergency caused by chemotherapy
neutropenic sepsis
which organisms are most dangerous in neutropenic sepsis?
gram negative e.g. pseudomonas
treating neutropenic sepsis
blood cultures
blind Abx therapy, 1st line tazocin
big complication of stem cell transplant?
graft vs host disease
symptoms of graft vs host disease
skin rash
diarrhoea
liver failure
How to prevent Graft vs Host disease?
T cell depletion of infused donor cells
immunosuppression of recipient
graft vs leukemia effect
A small degree of graft v host can be good as donor WBCs fight and kill leuemia cells
Acute Promyelocytic Leukemia
Subtype of AML, most curable of adult leukemias
What is disseminated intravascular coagulation (DIC)?
release of procoagulant material causing abnormal clotting throughout the body
common presentation of APML
they present with DIC or acute haemorrhage
gene abnormality seen in APML
t(15;17) PML-RARA rearrangement
prognosis of APML
80-90% 10yr survival
what does PML-RARA translocation create?
fusion oncogene
what is seen on blood film for APML?
what is seen on blood film for APML?
promyelocyte cells full of granules, prominent Auer rods
treatment for APML
All-trans retinoic acid (ATRA) and arsenic trioxide
mechanism of ATRA in APML?
binds to RARA and induces terminal differentiation of promyelocytes
mechanism of arsenic trioxide
degrades the PML-RARA fusion protein, induces apoptosis of promyelocytes
what monitoring is needed with ATRA-ATO regime?
QTc interval as arsenic can prolong it
W hat % of AML is APML?
how much of AML is APML?
11%
complication of ATRA treatment?
differentiation syndrome
complication caused by a large, rapid release of cytokines from promyelocytes
differentiation syndrome
complication caused by a large, rapid release of cytokines from promyelocytes
symptoms of differentiation syndrome
fever dyspnoea hypoxia pleural effusions renal dysfunction
treating differentiation syndrome?
corticosteroids e.g. dexamethasone
what is a risk factor for differentiation syndrome ?
high white cell count
what monitoring should you do after APML goes into remission?
minimal residual disease monitoring with PCR
Chronic Myeloid Leukemia (CML)
a form of leukemia characterized by overproduction of granulocytes
blood film in CML
myeloid cells at all stages of maturation
symptoms of CML
symptoms of CML
mostly after age 50. fatigue, malaise, low grade fever, wt loss, bone pains. night sweats, splenomegaly
treating CML
hydroxycarbamide
hydration
allopurinol
dasatinib/imatinib
gene mutation in CML
t(9;22) creating BCR-ABL
BCR-ABL
tyrosine kinase oncogene - fusion protein
Imatinib and dasatinib
Tyrosine kinase inhibitors of BCR-ABL
life expectancy for CML
normal if on treatment
purpose of hydroxycarbamide in CML treatment is to..
reduce white cell count
Chronic Lymphocytic Leukemia (CLL)
a form of leukemia characterized by extremely high levels of lymphocytes; most often found in middle-age adults
how do you diagnose CLL?
Flow cytometry
how do you diagnose CLL?
fatigue, shortness of breath, night sweats, lymphadenopathy, splenomegaly
what is the signature phenotype of CLL cells?
CD5 and CD19+ve B cells
symptom staging system for CLL
Binet system
A no impact
B lymphadenopathy
C reduction in Hb and/or platelets
what determines management in CLL?
whether p53 is wild type, mutated or deleted
treating CLL if wild type p53
standard chemo: fludarabine, cyclophosphamide, rituximab
treating CLL if mutated p53
targeted therapy with ibrutinib, venetoclax or idelalisib
ibrutinib
BTK inhibitor
venetoclax
BCL-2 inhibitor
Idelalisib
PI3K inhibitor
how does venetoclax work?
inhibits BCL-2 which stops apoptosis so apoptosis of CLL cells can occur
side effect of venetoclax
tumour lysis syndrome
Massive release of cellular breakdown products, medical emergency
Symptoms of tumour lysis syndrome
Massive release of cellular breakdown products, medical emergency
nausea and vomiting arrythmias seizures AKI death
treating tumour lysis syndrome
haemodialysis
how to prevent tumor lysis syndrome
Pretreat with IV fluids and allopurinol or rasburicase
Myeloproliferative disorders
a group of disorders considered clonal malignancies of the hematopoietic stem cell
myelofibrosis
replacement of bone marrow by fibrous tissue
primary myelofibrosis blood film
leucoerythroblastic, granulocyte left shift and teardrop red blood cells
granulocyte left shift
increase in proportion of immature leucocytes
symptoms of primary myelofibrosis
fatigue, shortness of breath, bloating, abdo discomfort (splenomegaly)
What mutation is myelofibrosis associated with?
JAK2 V617F mutation
treatment of primary myelofibrosis
hydroxycarbamide
Ruxolitinib
Ruxolitinib… inhibitor
JAK2 inhibitor
3 types of myeloproliferative disorders
primary myelofibrosis
polycythaemia vera
essential thrombocytothemia
how does V617F mutation cause myeloproliferation?
permanently activates JAK2 tyrosine kinase so overproduction of red cells and platelets
symptoms of multiple myeloma
CRAB:
hyperCalcemia
Renal insufficiency
Anemia
Bone/Back pain
investigations for multiple myeloma
FBC U&Es albumin LDH CRP electrophoresis light chain assay whole body MRI
mechanism of multiple myeloma
infiltration of bone marrow by plasma cells, causes bone marrow failure
Treating Multiple Myeloma
iv fluids
pamidronate (if hypercalcaemia)
haemodialysis
chemotherapy
chemotherapy for myeloma
Velcade, cyclophosphamide, thalidomide and dexamethasone
how to confirm myeloma diagnosis
bone marrow biopsy showing plasma cell infiltration
treating acute hypercalcaemia
hydration
pamidronate
Pamidronate
Pamidronic acid or pamidronate disodium or APD, is a nitrogen-containing bisphosphonate used to prevent osteoporosis.
Used in cancer
what do plasma cells produce in multiple myeloma?
monoclonal Ig, usually IgG sometimes IgA
what is light chain ratio in multiple myeloma?
abnormally skewed towards light chain
Monoclonal gammopathy of undetermined significance (MGUS)
no CRAB symptoms and less than 10% plasma cell infiltration
watch and wait
treating multiple myeloma?
chemotherapy
autologous stem cell transplant