Leukaemia Flashcards
List the 4 main types of leukaemia
Acute lymphoblastic leukaemia (ALL)
Chronic lymphocytic leukaemia (CLL)
Acute myeloid leukaemia (AML)
Chronic myeloid leukaemia (CML)
List the ways leukaemia patients may become severely ill
Infection
Bleeding
Hyper viscosity
What tests should you order for any leukaemia patient who complains they feel ill
FBC U&E LFT CRP LDH Blood cultures Ca2+ Glucose Clotting and INR CXR if clinically indicated
What must you know for any new leukaemia patient
The treatment plan - cure, prolong disease free survival or palliation
At what level of neutrophils is considered neutropenic?
<0.5X10^9/L
What risk assessment tool is used to predict the risk of serious complications in febrile neutropenia
MASCC score (multinational association for supportive care in cancer)
What does a MASCC score >21 indicate
Risk of septic complications is low and admission may be avoided
What variables are considered in the MASCC score?
Solid tumour/lymphoma Outpatient status at onset of fever Age <60yo Burden of illness - symptoms No hypotension (SBP>90) No COPD No dehydration
Give the flaws of the MASCC score
Symptom burden is subjective
Omission of potentially vital variables such as CRP
What should the MASCC score be used in conjunction with?
Clinical picture
Describe the management for someone with neutropenia
Full barrier nursing in side room, hand washing is vital
Avoid IM injection - risk of infected haematoma
Look for infection (mouth,axilla, perineum, IVI site) Take swabs
Check FBC, U&E, LFT, LDH, CRP, cultures x3 blood and hickman line, urine, sputum, stool if diarrhoea, CXR if clinically indicated
Wash perineum after defecation. Swab moist skin with chlorhexidine. Avoid unnecessary rectal exams. Oral hygiene and candida prophylaxis are important
Check vital signs 4hrly
High calorie diet - avoid foods with high risk of microbial contamination
Vases of flowers pose a pseudomonas risk
When should blind combination antibiotic therapy be started?
If temp >38 or Temp >37.5 on two occasions greater than an hour apart or if the patient is septic
How long should antibiotics be continued for in a neutropenic patient
Until afebrile for 72hrs or 5day course and until neutrophils >0.5x10^9/L
Give the blood results for tumour lysis syndrome
Increased potassium, urate and AKI
Describe hyper viscosity in leukaemia patients
If WCC>100x10^9/L WBC thrombi may form in the brain, lung and heart (leukostais)
Describe the pathophysiology of DIC
The release of procoagulants into the circulation causes widespread activation of coagulation, consuming clotting factors and platelets and causing increased risk of bleeding. Fibrin strands fill small vessels, haemolysing RBCs. Fibrinolysis is also activated
What causes DIC
Malignancy
Sepsis
Trauma
Obstetric events
What are some signs of DIC
Bruising
Bleeding anywhere (eg. venepuncture sites)
Renal failure
What do test results show in DIC
Decreased platelets
Increased PT and APTT
Decreased fibrinogen (correlates with severity)
Increased fibrin degradation products (D-dimers)
Film - broken RBCs (shistocytes)
How do you treat DIC
Treat the cause
Replace platelets if <50x10^9/L
Cryoprecipitate to replace fibrinogen
FFP to replace coagulation factors
What can be given to prevent sepsis in neutropenia?
Give fluoroquinolone (ciprofloxacin)
Granulocyte colony stimulators (G-CSF) can increase the production of WBCs (granulocytes) from bone marrow, but should not be given routinely in chemotherapy.
Herpes, pneumocystis and CMV prophylaxis has a role
What is acute lymphoblastic leukaemia
A malignancy of lymphoid cells, affecting B or T lymphocyte cell lineages, arresting maturation and promoting uncontrolled proliferation of immature blast cells with bone marrow failure and tissue infiltration
Which age group does ALL tend to affect?
Children aged 2-5yo
What is ALL associated with?
Ionizing radiation
Downs syndrome
Describe the 3 classifications of ALL
Morphological - The FAB system divides ALL into 3 types L1,L2,L3 by microscpic appearance
Immunological - surface markers are used to classify ALL into precursor B cell ALL, Tcell ALL and B cell ALL
Cytogenic - chromosomal analysis. Abnormalities are detected in up to 85% which are often translocations. Useful for predicting prognosis (eg. poor with Philadelphia chromosome - 9,22 translocation) and detecting disease recurrence
What are the signs and symptoms of ALL due to?
Infiltration
Marrow failure
Give the signs and symptoms of infiltration in ALL
Hepatosplenomegaly, lymphadenopathy, orchidomegaly, CNS involvement (meningism and CN palsies)
Give the signs and symptoms of bone marrow failure in ALL
Anaemia (decreased Hb)
Infection (decreased WCC)
Bleeding (decreased platelets)
What infections are common in those with ALL
Bacterial septicaemia Mouth Chest Perianal Skin Zoster CMV Measles Candidasis Pneumocystis pneumonia
What investigations should be performed in ALL and what may they show?
Blood film - characteristic blast cells
Bone marrow - characteristic blast cells
WCC - usually high
CXR and CT - mediastinal and abdominal lymphadenopathy
Lumbar puncture - look for CNS involvement
Which leukaemia commonly involves the CNS too
ALL
Describe the treatment of ALL
Education and motivation - increase pt compliance
Support - blood/platelet transfusion, IV fluids, allopurinol (prevent tumour lysis syndrome), insert SC port/hickman line for IV access
Infections - dangerous due to neutropenia, give IV ABx immediately and start neutropenic regime, give prophylactic antivirals, antifungals and ABx
Chemotherapy - complex, multi-drug, multi-phase regimens that may take many years: remission induction, consolidation and maintenance
Matched related allogenic marrow transplantation - once in 1st remission is the best option in standard risk younger adults
What is haematological remission of ALL defined as?
No evidence of leukaemia in the blood, normal/recovering blood count and <5% blasts in a normal regenerating marrow
What are the cure rates for ALL
Children = 70-90% Adults = 40%
What is associated with a poor prognosis in ALL
Adult Male Philadelphia chromosome Presentation with CNS signs Decreased HB WCC >100 B-cell ALL
What is the Philadelphia chromosome
BCR-ABL gene fusion due to translocation of chromosomes 9 and 22
What can be used to detect minimal residual disease?
PCR
Which chemo drugs increase prognosis for ALL in adults?
Rituximab/ibrutinib
What is acute myeloid leukaemia
Neoplastic proliferation of blast cells derived from marrow myeloid elements
Describe the prognosis of AML
Poor - death in 3 months if not treated, 20%3yr survival after treatment
Describe the incidence of AML
Commonest acute leukaemia in adults
1 in 10000 per year
What is associated with AML?
Increasing age Syndromes such as downs Radiation Myelodysplastic state Long term complication of chemotherapy eg. lymphoma
Describe the classification of AML
1) AML with recurrent genetic abnormalities
2) AML multilineage dysplasia
3) AML therapy related
4) AML other (M0-M7 maturation sub classification)
Describe the signs and symptoms of AML
Marrow failure - Anaemia and bleeding
Infiltration - hepatosplenomegaly, gum hypertrophy, skin involvement
Fever
Which subtype of AML presents with DIC
Acute promyelocytic leukaemia
Describe how acute promyelocytic leukaemia causes DIC
Thromboplastin release
Describe the diagnosis of AML
WCC may be high, normal or low
Few blasts in blood film - Auer rods (crystals of coalesced granules)
Diagnosis mainly by bone marrow biopsy, immunophenotyping and molecular methods
Cytogenic analysis guides treatment options and prognosis
List the complications of AML
Infection - candida and aspergillus
Tumour lysis syndrome
Leukostais
Describe the treatment for AML
Supportive care
Chemo - daunorubicin and cytarabine for 5 cycles given in 1 week blocks to get remission
Bone marrow transplant - cyclophosphamide and total irradiation, transplant and ciclosporin and methotrexate
What are some complication of bone marrow transplant
GVHD
Infection
Relapse
Infertility
What are myelodysplastic syndromes?
Heterogenous group of disorders that manifest as marrow failure and risk of life threatening infection and bleeding
What are the causes of myelodysplastic syndromes?
Most primary
Can be secondary to chemo and radiotherapy
What do tests show in myelodysplastic syndromes
Pancytopenia with reduced reticulocyte count
Marrow cellularity is increased due to ineffective haematopoiesis
Ring sideroblasts may also be seen in the marrow
Describe the treatment of myelodysplastic syndromes
Multiple red cell/platelet transfusions
G-CSF and EPO infusions
Allogenic stem cell transplantation
Low intensity treatments may lead to increased quality of life such as thalidomide analogues (lenalidomide) or hypomethylating agents (azacitidine and decitabine)
Give an example of a myeloproliferative disorder
Polycythaemia rubra vera - too many red cells
What is chronic myeloid leukaemia?
Characterized by an uncontrolled clonal proliferation of myeloid cells
What percentage of leukaemia is CML
15%
What age does CML occur?
40-60 yo
Which gender does CML affect more?
Male
What proportion of people with CML is the Philadelphia chromosome present in?
> 80%
Which patients have a worse prognosis in terms of the Philadelphia chromosome?
Ones without it
Give the symptoms of CML
Weight loss Tiredness Fever Swears Gout Bleeding Abdominal discomfort
What are the signs of CML
Splenomegaly
Hepatomegaly
Anaemia
Bruising
What tests diagnose CML
Increased WCC Increased neutrophils, basophils, eosinophils, monocytes Decreased Hb Platelets variable Increased urate Increased B12 Bone marrow hypercellular Cytogenetic analysis of blood or bone marrow for Ph
Describe the natural history of CML
Variable with median survival 5 or 6 years
3 phases
Chronic - lasting months or years of few symptoms
Accelerated phase - increased symptoms, spleen size and difficulty controlling counts
Blast transformation - features of acute leukaemia and death
Describe the treatment of CML
BCR-ABL inhibitors - monoclonal antibody - imatinib
Stem cell transplant
Give the side effects of imatinib
Nausea Cramps Oedema Rash Headache Arthralgia Myelosuppression
Describe CLL
The hallmark is progressive accumulation of malignant clone of functionally incompetent B cells
What influences the risk of CLL
Mutations
Trisomy’s
Deletions
What staging system is used in CLL
Rai
What symptoms present with CLL
Often none, surprise finding on FBC
Patients may be anaemia, infection prone, decreased weight, sweats, anorexia
What are some signs of CLL
Enlarged, rubbery, non tender nodes, splenomegaly, hepatomegaly
What investigations are done in CLL?
Increased lymphocytes
Later - autoimmune haemolysis, marrow infiltration, decreased Hb, Decreased neutrophils, Decreased platelets
What are the complications of CLL
Autoimmune haemolysis Increased Infection due to hypogammaglobinaemia (decreased IgG) Bacterial Vital especially herpes zoster Marrow failure
What is the first line chemo for CLL
Fludarabine
Rituximab
Cyclophosphamide
Describe the natural history of CLL
1/3 never progress (or even regress)
1/3 progress slowly
1/3 progress actively
What is death from CLL often due to?
Infection
Transformation to aggressive lymphoma (Richter’s)
