Haem Cancer

Question	Answer
Complications of leukaemia	infection bleeding hyperviscosity tumour lysis syndrome DIC
How would you manage a case of neutropenic sepsis secondary to leukaemia?	Prevention: full barrier nursing, hand washing, side room. Avoid IM injections (infected haematoma risk). Oral hygeine (H202 mouthwash/2h & candida prophylaxis). Wash perineum after defacation. Investigation: look for infection - urine, blood x 3, sputum, stool, CXR. Bloods - FBC, U&E, LFT, INR
ALL pathophysiology	Affects B & T cell lymphocyte lines Uncontrolled proliferation of immature blast cells Bone marrow failure Tissue infiltration X rays during pregnancy and Down's syndrome are risk factors Commonest cancer of childhood, rare in adults. CNS involvement is common.
How would you classify ALL?	1.Morphology: FAB system divides into L1, L2 & L3 by microscopic appearance. Limited use. 2. Immunology: surface markers group into precursor B cell, T cell, or B cell. 3. Cytogenetics: Chr analysis to look for abnormalities (often translocations), useful for prognosis e.g. poor with Philadelphia chr, & for detecting disease recurrence.
Signs & Sx of ALL	Marrow failure --> anaemia, infection, bleeding Infiltration --> hepatosplenomegaly, lymphadenopathy (superficial or mediastinal), orchidomegaly, CNS involvement ( CN palsies, meningism)
Common infections in ALL	Chest, mouth, perianal, skin Bacterial septicaemia, Herpes zoster (chickenpox/shingles), CMV, measels, candidiasis, Pneumocystis pneumonia
Ix in ALL	WCC high Blood film & bone marrow --> blast cells CXR & CT to look for mediastinal & abdo lymphadenopathy LP to exclude CNS involvement
Supportive Tx in ALL	Transfusion (blood/plts) IV fluids Allopurinol (tumour lysis syndrome prevention) Hickman line (IV access)
Chemo Tx in ALL	1. Remission induction = vincristine, prednisolone, L-asparaginase + daunorubicin 2. Consolidation = high/medium dose therapy in 'blocks' over several weeks 3. CNS prophylaxis = intrathecal (or high dose IV) MTX + CNS irradiation 4. Maintenance = prolonged chemo for 2 yrs e.g. metocaptopurine daily, MTX weekly, vincristine + prednisolone monthly. Relapse common in blood, CNS & testes -therefore check at follow up.
Principles of Tx in ALL	1. Supportive Tx e.g. transfusions 2. Chemo 3. Infection Tx secondary to neutropaenia (from disease or Tx) 4. Matched related allogeneic marrow transplant (best Tx when in 1st remission in standard-risk, younger adults)
Define Haematological remission	1. No evidence of leukaemia in the blood 2. Normal or recovering blood count 3. <5% blasts in a normal, regenerating marrow
Prognosis in ALL	Cure rates 70-90% in children, but only 40% in adults Poor prognostic factors = adult, male, Philadelphia chr, BCR-ABL gene fusion, presentation with CNS signs, low Hb, WCC> 100, B cell-type ALL
Parotid swelling differential	Acute - Mumps, HIV Unilateral, recurrent - Stone Chronic, bilateral - Bulimia, Myxoedema, ALL/tumour, AI disease (hypoT, Sjogrens) Sarcoid, amyloid, Wegener's
AML pathophysiology & epidemiology	blast cells derived from myeloid lineage rapid progression (death in 2mo if untreated) 20% survival rate @ 3yrs after Tx Commonest acute leukaemia of adults; incidence incr with age (ALL = children, AML = adults) Assoc with myelodysplastic states, radiation & syndromes e.g. Down's
AML classification	WHO histological classification: 1. AML with recurrent genetic abnormalities 2. AML multi-lineage dysplasia (usually secondary to existing MDS) 3. AML therapy related 4. AML, other 5. Acute leukaemias of ambiguous lineage (myeloid and lymphoid)
Signs and Sx of AML	Marrow failure --> anaemia, infection, bleeding. DIC is common with the promyelocytic subtype. Infiltration --> hepatosplenomegaly, gum hypertrophy, skin involvement (CNS involvement a presentation is rare in AML, common in ALL)
Diagnosis and Ix for ALL	WCC raised, (may be normal or low) NEED a BM biopsy, as blast cells may be sparse in blood Differentiate from ALL via immunophenotyping/molecular methods Cytogenetic analysis (e.g. type of mutation) guides Tx and prognosis
Complications of AML	1. Infection (disease & during Tx)- beware as AML itself can cause a fever and common organisms can present oddly. 2. Tumour lysis syndrome - incr plasma urate levels, so give allopurinol & IV fluids with chemo 3. Leukostasis if WCC v high
Principles of Tx of AML	1. supportive e.g. transfusions like ALL 2. Chemo 3. Bone marrow transplant In elderly pts --> supportive care or low dose chemo for disease control may be more appropriate
Chemo in AML	V intense, long periods of marrow suppression (low N & plts) Main drugs - daunorubicin, cytarabine 5 cycles in 1 week blocks to achieve remission
Bone marrow transplant in AML	Allogeneic transplants (from matched siblings/donors) indicated in first remission with poor prognosis 1. destroy leukaemic cells and immune system with cyclophosphamide and total body irradiation 2. repopulate marrow from a matched donor via IV infusion 3. Ciclosporin + MTX reduce risk of new marrow attacking the patient's body (graft vs host disease) Complications - graft vs host disease, opportunistic infections, relapse of leukaemia, infertility Autologous BMT (from the patient) - indicated with intermediate prognosis
Myelodysplastic syndromes (MDS/myelodysplasia) What is it and how would you diagnose it?	Group of disorders characterised by marrow failure, leading to life-threatening infection and bleeding. Most are primary, but may be secondary to chemo or radio. 30% transform to acute leukaemia. Ix - FBC (pancytopaenia), film (low retic count), marrow (incr cellularity due to ineffective haematopoeisis; ring siderobasts)
Tx of MDS	multiple transfusions EPO & G-CSF may reduce transfusions Immunosuppression - ciclosporin, antithymocyte globulins Curative allogeneic (from donor) stem cell transplant (but often can't as pts >70yrs old) Thalidomide analogues for low risk MDS Hypomethylating agents for symptomatic MDS Median survival 6mo to 6y according to type
What is Philadelphia chromosome?	hybrid chromosome, reciprocal translocation of 9 & 22, forming a fusion gene BCR/ABL on chr 22 that has tyrosine kinase activity Present in >80% with CML
CML	myeloid cell proliferation 15% of leukaemias 40-60 year olds most common slightly more males rare in childhood
Signs and Sx of CML	chronic, insidious weight loss, tiredness, fever, sweats Gout (purine breakdown) Bleeding (plt dysfunction) abdo discomfort (large spleen)
Ix in CML	30% detected by chance. WBC v high - often >100 All myeloid cells raised - Neutrophils, myelocytes, basophils, eosinophils Urate & B12 incr Marrow - hypercellular Phil chr found by cytogenetic analysis of blood or BM
Prognosis in CML	median survival 6 yrs Phase 1 - chronic (months - years) with few Sx Phase 2 - accelerated phase, incr Sx, spleen size & difficulty controlling counts Phase 3 - blast transformation with features of acute leukaemia, +/- death
Chemo Tx of CML	Imatinib - BCR/ABL tyrosine kinase inhibitor. Response rate >90%. alpha-IFN - the old gold standard, that may still have a role in combo therapy or 2nd line. Hydroxycarbamide - another 2nd line option Dasatinib (more potent BCR/ABL inhibitor)
Stem cell Tx in CML	allogeneic (from donor) - only curative Tx but bears high mortality & morbidity. Only use first line in young pts (low mortality rates) Offer everyone else imatinib 1st line R/v annually to decide whether to cont. imatinib, offer combo Tx, or stem cell transplant.
What is CLL?	Mature B cell accumulation Commonest leukaemia (>25% incidence) M>F (2:1)
Staging CLL	Rai staging system (with median survivals) 0 = lymphocytosis alone (>13y) 1 = lymphocytosis + lymphadenopathy (8y) 2 = lymphocytosis + spleno or hepatomegaly (5y) 3 = lymphocytosis + anaemia <11 (2y) 4 = lymphocytosis + plts <100 (1y)
Signs and Sx of CLL	incidental on FBC (incr lymphocytes) anaemic, infection prone weight loss, sweats, anorexia in severe cases enlarged, rubbery, non-tender nodes hepatosplenomegaly Later - autoimmune haemolysis, marrow infiltration, low Hb, low N, low plts

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	Created by Luke Granger over 10 years ago