Blood cancers Flashcards
Define ALL
• Malignancy of the bone marrow and blood characterised by the proliferation of lymphoblasts (primitive lymphoid cells)
Pathophysiology of ALL
- Lymphoblasts undergo malignancy transformation and proliferation
- This leads to the replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues
RF of ALL (9)
- Environmental (Radiation, Smoking, Viral Infection)
- Genetic (Down’s syndrome, Neurofibromatosis type 1, Fanconi’s anaemia, Xeroderma Pigmentosum)
- Age < 6 or mid-late 30s/mid 80s
- Family history
- History of malignancy
Epidemiology of ALL
- MOST COMMON malignancy of CHILDHOOD
- Peak incidence: 2-5 yrs old
- There is a second peak in incidence in the elderly
- Annual UK incidence: 1/70,000
In which 2 ways does ALL manifest
Bone marrow failure and organ infiltration
S/s of ALL (8 for 1 manifestation, 14 in the other)
• Symptoms of Bone Marrow Failure: o Anaemia (fatigue, dyspnoea) o Bleeding (spontaneous bruising, bleeding gums, menorrhagia) o Opportunistic infections o Pallor o Bruising o Bleeding o Infection
• Symptoms of Organ Infiltration: o Tender bones o Enlarged lymph nodes o Mediastinal compression o Meningeal involvement (headache, visual disturbances, nausea) o Lymphadenopathy o Hepatosplenomegaly o Cranial nerve palsies o Retinal haemorrhage o Papilloedema on fundoscopy o Leukaemic infiltration of the anterior chamber of the eye o Testicular swelling
Ix for ALL (11)
• Bloods o FBC - normochromic normocytic anaemia, low platelets, variable WCC o High uric acid o High LDH o Clotting screen • Blood Film o Abundant lymphoblasts
• Bone Marrow Aspirate or Trephine Biopsy
o Hypercellular with > 20% lymphoblasts
• Immunophenotyping - using antibodies to recognise cell surface antigens
• Cytogenetic - karyotyping to look for chromosomal abnormalities or translocations
• Cytochemistry
• Lumbar Puncture - check for CNS involvement
• CXR - may show mediastinal lymphadenopathy, lytic bone lesions
• Bone Radiographs - mottled appearance with punched out lesions due to leukaemic infiltration
Define AML and how is it classified
AML describes malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the bone marrow and blood (clonal expansion of myeloid blasts in bone marrow, peripheral blood or extramedullary tissues).
Classified using the FAB (French-American-British) System into 8 morphological variants (M0-M7).
Pathophysiology of AML
- Myeloblasts undergo malignant transformation and proliferation
- This leads to replacement of normal marrow and bone marrow failure
- Usually due to mutations of transcription factors
RF of AML (5)
- Age > 65
- Family history
- Radiation Exposure
- Benzene Exposure
- History of chemotherapy
Epidemiology of AML
- MOST COMMON acute leukaemia in ADULTS
- Incidence INCREASES with age
S/s of AML (9 for 1 manifestation, 8 in the other)
• Symptoms of Bone Marrow Failure: o Anaemia (lethargy, dyspnoea) o Bleeding (due to thrombocytopaenia or DIC) o Opportunistic or recurrent infections o Pallor o Cardiac flow murmur o Ecchymosis o Bleeding o Opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections)
• Symptoms of Tissue Infiltration:
o Gum swelling or bleeding
o CNS involvement (headaches, nausea, diplopia)
o Hepatosplenomegaly
o Skin rashes
o Gum hypertrophy
o Deposit of leukaemic blasts in the eye, tongue and bone (RARE)
Ix for AML (8)
• Bloods o FBC - low Hb, low platelets, variable WCC o High uric acid o High LDH o Clotting studies, fibrinogen and D-dimers (to check for DIC) • Blood Film o Myeloblasts o Auer Rods o Bilobed nucleus/indented nucleus • Bone Marrow Aspirate or Biopsy o Hypercellular with > 20% blasts o Biopsy is diagnostic • Immunophenotyping o Antibodies against surface antigens used to classify the lineage of the abnormal clones – this is to differentiate from ALL • Cytogenetics – helps decide treatment and guide prognosis • Immunocytochemistry
Define CLL
• Characterised by progressive accumulation of functionally incompetent mature B cells, which are monoclonal in origin, which have escaped programmed cell death. There is an overlap between CLL and non-Hodgkin’s lymphoma
Chromosomal changes leading to CLL
o Trisomy 12
o 11q and 13q deletions
RF of CLL (3)
- Age > 60 (median age at diagnosis is 70)
- Male, white ethnicity
- Family history of CLL
Epidemiology of CLL
- 90% are > 50 yrs
- Commonest leukaemia – incidence 4/100,000/yr
- More common in MALES
- Rare in Asians
S/s of CLL (12)
• Asymptomatic - 40-50% of cases are diagnosed following routine blood tests • May be anaemic or infection-prone • Systemic Symptoms: o Lethargy o Malaise o Night sweats • Symptoms of Bone Marrow Failure: o Recurrent infections o Herpes zoster infection o Easy bruising or bleeding • If severe: weight loss, sweats, anorexia
• Non-tender lymphadenopathy – enlarged, rubbery, non-tender
• Hepatomegaly
• Splenomegaly
• LATE STAGE signs of bone marrow failure:
o Pallor
o Cardiac flow murmur
o Purpura/ecchymosis
Ix for CLL (FBC 6, 3 others)
• Bloods
o FBC
• Lymphocytosis – marked raised lymphocytes
• Low Hb
Could be due to bone marrow infiltration, hypersplenism or autoimmune haemolysis
• Low platelets – marrow infiltration
• Low serum Ig – marrow infiltration
• Low neutrophils – marrow infiltration
• Later: autoimmune haemolysis
• Blood Film
o Small lymphocytes with thin rims of cytoplasm
o Smudge cells
• Bone Marrow Aspirate or Biopsy
o Lymphocytic replacement of normal marrow
• Cytogenetics
What can CLL be associated with
CLL may be associated with autoimmune phenomena such as haemolytic anaemia (warm agglutinins) or thrombocytopaenia/