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Chapter: Medicine Study Notes : Haematology and Immunology


Cancer dominantly of white cells arising in MARROW. Lymphoma primarily arises in lymph nodes



·        Leuk: Greek for white

·        = Cancer dominantly of white cells arising in MARROW.  Lymphoma primarily arises in lymph nodes

·        Summary:


Chronic Leukaemia


·        Chronic Myeloblastic Leukaemia (CML): Converts to AML/AGL.


·        Chronic Lymphoblastic Leukaemia (CLL)


Acute Leukaemia


·        Rapid onset, 100% mortality within 3 months if untreated

·        Very undifferentiated (anaplastic) cells: blasts, no normal cells in blood

·        Types: 

o   Acute Myeloblastic Leukaemia (AML). Chance of cure with chemo alone = 20 – 40%. With transplant = 60%. Has Auer rob in blast

o   Acute Lymphoblastic Leukaemia (ALL)

·        Presentation:

o   Tired due to anaemia, breathless 

o   Bleeding due to ¯platelets, nose bleeds

o   Bacterial infection

o   Hepatosplenomegaly, ­lymph nodes, bone pain (push on sternum)

·        Investigations: 

o   FBC: ¯Hb, ¯platelets, white count: High, normal or low (sometimes leukaemia cells stay in marrow) 

o   Bone marrow: > 30% of nucleated cells in the marrow are leukaemic blasts

·        Classification:

o   Cytochemistry: 

§  Staining.  PAS - +ive stain for glycogen Þ lymphoblastic

§  Sudan black +ive for peroxidase Þ myeloblastic

o   Immunology: flow cytometry

o   Cytogenetics 



·        Supportive Care:

o   Antibiotics, platelet/RBC transfusion

o   Venous catheter: Hickman catheter

·        Cytotoxic Treatment:

o   Complex multi-drug protocols 

o   Remission induction: 1-4 weeks depending on protocol. FBC normal and < 5% blasts in marrow (that‟s normal). AML – achieved in 70 – 80%. ALL – achieved in 70 – 80% of adults, 95% of kids 

o   Consolidation: more drugs to mop up residual blasts, including CNS prophylaxis (some drugs don‟t penetrate CNS well)

o   But 60 – 80% chance of relapse over next 2 – 4 years

·        Bone Marrow Transplantation:

o   = Haematopoietic stem cell transplantation

·        ­Kill of leukaemic cells with ­dose: but limited by marrow toxicity. With marrow transplantation can push dose higher (limit is organ toxicity) if cancer is responsive 

·        Process: patient and donor preparation, conditioning (chemo & high does radiation), stem cell infusion, neutropenic phase, post neutropenic phase 

·        Sources of stem cells: Self (autologous), twin (syngenic), HLA matched sibling (allogenic), HLA partial matched sibling, matched unrelated donor (MUD)

·        Peritransplant mortality = 20%


Fever in a Neutropenic Patient


·        Eg in patients undergoing chemotherapy

·        Indicators of serious infection:

o  Signs and symptoms of infection will be reduced – can‟t mount an inflammatory response

o  Temperature:

§  > 38.5 C

§  > 38 for 4 hours

§  Patient fells unwell but no temperature

o  Neutropenia: 

§  Neutrophils < 0.5 * 10E9/L (less than 0.2 Þ serious concern)

§  Neutrophils falling

§  Prolonged neutropenia (> 7 days)

·        Types of infection (drives focused history)

o  Respiratory: SOB, cough

o  Skin infection

o  Mouth and teeth

o  Perianal (pain on moving bowels and wiping)

o  Pain around central line

o  Less often: bowel & UTI

·        Focused exam:

o  Signs of septic shock: Pulse, BP and peripheral circulation

o  Chest: percussion and auscultation

o  Mouth: a good look around – abscesses will be sensitive to pain

o  Skin infections, especially lines

o  Quick abdominal 

o  Exam perianal area – test for sensitivity to touch. Don‟t do PR (risk of minor trauma ® bacteraemia) 

·        Investigations:

o  FBC

o  Blood culture (debate about whether to take it from the central line or not)

o  CXR

o  Swabs from anything that looks infected, including central line 

o  Maybe CRP: ­ in bacteraemia

·        Normally don‟t find anything.  Over half infections are low grade line infections

·        If in doubt, treat empirically now.  If infected will deteriorate quickly:

o  Gentamycin + Ticarcillin (synthetic penicillin)

o  Monotherapy (eg imipenem)

o  +/- Vancomycin (for staph line sepsis)

·        Causes of infection:


·        Subsequent fevers: longer in hospital (­hospital acquired infection), longer on antibiotics, etc

·        If fever persists:

o   Repeat the above exam and investigations – but unlikely to add anything new

o   Choices:

§  Change antibiotics

§  Consider antifungal: Amphotericin.  Watch for nephrotoxicity and the patient feels awful

·        Obscure fevers:

o   Central venous line infection

o   Occult sinusitis (check with CT) 

o   Hepatosplenic candidiasis (check with CT ® abscess ® biopsy)

o   Pulmonary/disseminated aspergillus (doesn‟t respond to amphotericin)

o   Viral

o   Drugs

·        Prevention:

o   Avoid hospitalisation

o   Strict hand washing

o   Avoid invasive procedures (beware interventionist surgeons!)

o   Care of IV devices

o   Consider prophylactic antimicrobials

·        Prophylaxis 

o   Bacteria: selective gut decontamination (origin of many infections is bowel flora): Ciprofloxacin (fluorinated quinolone). Arguments for and against 

o   Anti-fungal: Fluconazole, Itraconazole (OK for prophylaxis, not so good as amphotericin for established infection) 

o   Anti-viral: acyclovir (for HSV), ganciclovir (for CMV)

o   Anti-pneumocystis: co-trimoxazole (but beware marrow suppression) or aerolised pentamidine

·        Other possible treatments: 

o   Granulocyte-CSF: try to ­ marrow production of neutrophils

o   Maybe g-globulin infusions

o   Transfuse granulocytes: emerging area


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