Haematological Malignacies Flashcards
Define myelomas
Proliferation of plasma cells
- terminal cell of B lymphocyte
- release immunoglobulins - non-functioning
Features of myelomas
Bone marrow infiltration -> anaemia/thrombocytopenia
Cause bone and renal disease
Can form solid tumours of plasma cells (plasmacytomas)
Impaired immune system
Treatable but not curable
Myeloma presentation
Bones - generalised osteopenia - pathological fractures Hypercalcaemia - polyuria, polydipsia, abdo pain, constipation, lethargy, confusion Bone marrow infiltration - anaemia - thrombocytopenia - neutropenia Infections Hyperviscotisy syndrome - visual disturbance - headache - - - -
What define myeloma
Myeloma defining events S - 60% BM plasmacytosis Li - light chain ratio > 100 M - > 1 focal lesions on MRI > 5 mm Evidence of end organ damage C - calcium elevation > 2.75 R - renal impairment Cr>117 A - anaemia Hb < 100 B - bone lesion
Define haemopoiesis
Formation of blood cells from a hemopoietic stem cell
- cell isolated from blood or bone marrow can renew itself
- able to differentiate to a variety of specialised cells
Where does haemopoiesis go wrong
Loss of normal tight controls on haemopoiesis - too many cells proliferating - don't apoptose/die when should - don't differentiate (maturation arrest) Myeloid - acute myeloid leukaemia - chronic myeloproliferative neoplasms Lymphoid - acute lymphoblastic leukaemia - chronic lymphoblastic leukaemia - lymphoma
Leukaemia vs lymphoma
Leukaemia - affecting mainly bone marrow with or without released circulating neoplastic cells in blood
Lymphoma - predominantly nodal or organ-based
Define leukaemia
Cancer of stem cell line in bone marrow
Increase in number of white blood cells
Classification of leukaemia
Myeloid vs lymphoid
- depends on which lineage is involved
Acute vs chronic
- based on maturity of cells
- acute has proliferation of immature blast cells
- chronic has proliferation of more mature cells
- pace of disease faster in chronic
Define myeloproliferative neoplasms
Chronic proliferation of myeloid cells
Red = polycythaemia
Platelets = thrombocythemia
White = leukaemia (CML)
Features of bone marrow
Where blood cells develop
Mostly found in pelvis, vertebrae, ribs and sternum
Development of blood cells
Pluripotent haematopoietic stem cells
- undifferentiated cells that have the potential to become - myeloid stem cells, lymphoid stem cells and dendritic cells
Red blood cells
- develop from reticulocytes that come from myeloid stem cells
- survive up to 3 months
Platelets
- made by megakaryocytes
- lifespan of 10 days
White blood cells
- myeloid stem cells become promyelocytes
- monocytes then macrophages
- neutrophils
- eosinophils
- mast cells
- basophils
- lymphocytes come from lymphoid stem cells - become B and T cells
- B lymphocytes mature in the bone marrow and differentiate into plasma or memory B cells
- t lymphocytes mature in thymus gland and differentiate into CD4 cells (T helper), CD8 cells (cytotoxic T cells) and natural killer cells
Features of blood films
Anisocytosis - variation in size of red blood cells
- myelodysplastic syndrome as well as anaemia
Target cells - central pigmented area surrounded by pale area surrounded by ring of thicker cytoplasm
- iron deficiency anaemia and post-splenectomy
Heinz bodies - individual blobs seen inside RBC caused by denatured globin
- G6PD and alpha-thalassaemia
Howell-Jolly bodies - individual blobs of DNA material seen in RBC, normally removed by spleen
- post-splenectomy and severe anaemia
Reticulocytes - larger immature RBC, still have RNA material
- haemolytic anaemia
Schistocytes - fragments of RBCs
- haemolytic uraemic syndrome, DIC, thrombotic thrombocytopenia purpura, metallic heart valves, haemolytic anaemia
Sideroblasts - immature RBC that contain blobs of iron, occur when bone marrow unable to incorporate iron into haemoglobin
- myelodysplasic syndrome
Smudge cells - ruptured WBC, occur during process of preparing the blood film due to aged or fragile WBC
- chronic lymphocytic leukaemia
Spherocytes - spherical RBCs
- autoimmune haemolytic anaemia or hereditary spherocytosis
Define anaemia
Low level of haemoglobin
- women 120-165
- men 130-180
Causes of microcytic anaemia
TAILS
- thalassaemia
- anaemia of chronic disease
- iron deficiency anaemia
- lead poisoning
- sideroblastic anaemia
Causes of normocytic anaemia
3As and 2Hs
- acute blood loss
- anaemia of chronic disease
- aplastic anaemia
- haemolytic anaemia
- hypothyroidism
Causes of macrocytic anaemia
Megaloblastic - result of impaired DNA synthesis preventing cell from dividing normally - B12 or folate deficiency Normoblastic - alcohol - reticulocytosis - hypothyroidism - liver disease - azathioprine
Symptoms of anaemia
Fatigue SOB Headaches Dizziness Palpitations
Specific symptoms of iron deficiency anaemia
Pica - dietary cravings
Hair loss
Signs of anaemia
General - pale skin - conjunctival pallor - tachycardia - raised RR Specific - koilonychia, angular cheilitis, atrophic glossitis - iron deficiency - jaundice - haemolytic - bone deformities - thalassaemia
Ix for anaemia
Haemoglobin Mean Cell Volume (MCV) B12 Folate Ferritin Blood film
Causes of iron deficiency anaemia
Blood loss - most common in adults - menorrhagia - GI tract cancer Dietary insufficiency - most common in growing children Poor iron absorption Increased requirements during pregnancy
Features of iron deficiency
Ferritin - form of iron when deposited and stored in cells
- low suggestive of iron deficiency
- high is difficult to interpret as related to inflammation
Serum iron - varies throughout day
Total iron binding capacity - marker for how much transferrin is in blood
Transferrin saturation - good indication of total iron in body
Mx of iron deficiency anaemia
Blood transfusion
Iron infusion
Oral iron
Pathophysiology of pernicious anaemia
Autoimmune condition
Antibodies form against parietal cells or intrinsic factor preventing absorption of vitamin B12
Symptoms of B12 deficiency
Peripheral neuropathy with numbness or paraesthesia
Loss of vibration sense or proprioception
Visual changes
Mood or cognitive changes
Ix for B12 deficiency
Testing for auto-antibodies
- intrinsic factor antibody - 1st line
- gastric parietal cell antibody
Mx of B12 deficiency anaemia
Dietary deficiency - oral replacement - cyanocobalamin
Pernicious anaemia - 1mg IM hydroxycobalamin 3x weekly for 2 weeks, then every 3 months
Define autoimmune haemolytic anaemia
Antibodies created against patients RBCs
Leads to destruction of RBC
Types of autoimmune haemolytic anaemia
Warm - more common - haemolysis occurs at normal or above normal temperatures - idiopathic Cold - antibodies attach at lower temperatures causing RBC to clump together - agglutination -> destruction of RBC - secondary to other conditions - lymphoma - leukaemia - SLE - EBV - CMV - HIV
Mx of autoimmune haemolytic anaemia
Blood transfusions
Prednisolone
Rituximab - monoclonal antibody against B cells
Splenectomy
Define thalassaemia
Genetic defect in protein chains that make up haemoglobin
- defects in alpha-globin -> alpha thalassaemia - chromosome 16
- defects in beta-globin -> beta thalassaemia - chromosome 11
Both autosomal recessive
Clinical features of thalassaemia
Microcytic anaemia (low mean corpuscular volume) Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead and malar eminences
Ix for thalassaemia
FBC - microcytic anaemia
Haemoglobin electrophoresis
DNA testing
Complications of thalassaemia
Iron overload
- faulty RBC, recurrent transfusions and increased iron absorption
Monitor serum ferritin
Mx involves limiting transfusions and iron chelation
Mx of alpha-thalassaemia
Monitoring the full blood count Monitoring for complications Blood transfusions Splenectomy may be performed Bone marrow transplant can be curative
Types of beta-thalassaemia
Minor
- one normal and one abnormal gene
- causes mild microcytic anaemia
Intermedia
- two defective genes or one defective and one deletion
- more significant microcytic anaemia
Major
- homozygous for deletion genes
- severe anaemia and failure to thrive in early childhood
- causes severe microcytic anaemia, splenomegaly and bone deformities
Define sickle cell anaemia
Genetic condition that causes sickle shaped red cells
Pathophysiology of sickle cell anaemia
Foetal haemoglobin replaced by haemoglobin A at around 6 weeks
Patients with sickle cell have abnormal haemoglobin variant S
- causes red blood cells to sickle
Autosomal recessive
Abnormal gene for beta-globin on chromosome 11
Complications of sickle cell anaemia
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as the hip Pulmonary hypertension Painful and persistent penile erection (priapism) Chronic kidney disease Sickle cell crises Acute chest syndrome
Mx of sickle cell
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin)
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
Define sickle cell crisis
Umbrella term for spectrum of acute crises related to the condition
Occur spontaneously of triggered by stresses
- infection
- dehydration
- cold
- significant life events
Mx of sickle cell crisis
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
Types of leukaemia
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
Pathophysiology of leukaemia
Genetic mutation in one of the precursor cells leads to excessive production of single type of abnormal WBC
Suppression of the cell lines -> pancytopenia
- low RBC - anaemia
- low WBC - leukopenia
- low platelets - thrombocytopenia
Epidemiology of leukaemia
Under 5 and over 45 - ALL
Over 55 - CLL
Over 65 - CML
Over 75 - AML
Presentation of leukaemia
Non-specific - need urgent FBC Fatigue Fever Failure to thrive (children) Pallor due to anaemia Petechiae and abnormal bruising due to thrombocytopenia Abnormal bleeding Lymphadenopathy Hepatosplenomegaly
Differential diagnosis of petechiae
Caused by thrombocytopenia
- leukaemia
- meningococcal septicaemia
- vasculitis
- idiopathic thrombocytopenia purpura
- non-accidental injury
Ix for leukaemia
FBC - within 48 hrs Blood film LDH - raised but not specific CXR - infection or mediastinal lymphadenopathy Lymph node biopsy Lumbar puncture - if CNS involvement CT/MRI/PET for staging and assessing
Types of bone marrow biopsy
Bone marrow aspiration - taking liquid sample full of cells Bone marrow trephine - solid core sample of bone marrow - better assessment of cells and structure Bone marrow biopsy - usually taken from iliac crest - local anaesthetic and specialist needle - samples can be examined straight away
Define Acute Lymphoblastic Leukaemia
Malignant change in one the lymphocyte precursor cells
- > acute proliferation of a single type of lymphocyte - usually B lymphocytes
- > replace other cell types created by bone marrow - pancytopenia
Epidemiology of ALL
Most common cancer in children - peaks 2-4 years Also affects adults over 45 Associated with Downs syndrome Associated with Philadelphia chromosome translocation
Features of blood film of ALL
Blast cells - large cell with very large nucleus
Define chronic lymphocytic leukaemia
Chronic proliferation of single type of well differentiated lymphocyte - usually B lymphocytes
Epidemiology of CLL
Adults over 55
Can transform into high-grade lymphoma - Richter’s transformation
Clinical features of CLL
Asymptomatic Infection Anaemia Bleeding Weight loss Can cause warm autoimmune haemolytic anaemia
Blood film features of CLL
Smear or smudge cells
- aged or fragile WCC rupture leaving a smudge on the film
Features of chronic myeloid leukaemia
3 phases - chronic - accelerated - blast Associated with Philadelphia chromosome
Feature of chronic phrase of CML
Lasts around 5 years
Often asymptomatic - patients diagnosed incidentally with raised WCC