4Blood Cell ComponentsLymphocytes form in marrow – T cells mature in the thymus. B and T cells are deposited in lymph organs (e.g. spleen) and circulate in lymphatic system.Myeloid cells include all other haematological cell types, which form in bone marrow before release into vascular space.
5LeukaemiaLeukaemic cells (cancerous WBC) infiltrate bone marrow, affecting normal function, i.e. There is inadequate haematopoeisis.Aetiology mostly unknown, but viruses/chemicals/drugs/radiation all implicated
7Leukaemia: Signs & Symptoms Mostly seen in acute leukaemia, late chronic.Due to bone marrow failure – red marrow in central skeleton and proximal long bones
8Leukaemia: Investigations FBC – Hb low, WBC usually highBlood film – shows precursor lymphoblast cellsBone Marrow aspirate – increased cellularity, reduced erythropoeisis, reduced megakaryocytes - replaced by blastsCXR – why?LP for CSF examination in ALL
9Leukaemia: TreatmentWithout treatment, acute leukaemia is invariably fatal within months.ALL in the young has best chance of cure, AML good chance of cure but secondary AML poorest prognosis.Curative treatment carries both morbidity and mortality – Risk vs Benefit
10Leukaemia: Treatment All need supportive treatment: Curative Intent: Transfusions of red cells and platelets and necessary, prevention of infection, treatment of infection with antibiotic/antifungal agents as soon as fever developsCurative Intent:Try to return marrow to normal – complete remission (CR). ‘Induction chemo’ not specific to cancerous cells – major infection risk. Followed by specific ‘consolidation’ regimen – ESSENTIAL or remission will certainly occur.
11Acute Myeloid Leukaemia Treatment with curative intent if <60Risk and prognosis based on bone marrow resultBone marrow transplant in some higher risk patients, or if fail 2 cycles chemo75% achieve CR, 50% of those are ‘cured’ (1/3 overall)
12Acute Lymphocytic Leukaemia ALL commonest childhood malignancy, but can be any ageCR and consolitation achieved with different agents than in AMLEarly transplant if high risk (older pts, high WCC, >3-4 weeks to achieve CR)Major difference is need to treat CNS as soon as CR achieved – intrathecal chemoVery high risk may need cranial radiotherapyMaintenance Tx for at least 2 years
13Acute LeukaemiasALL in childhood good prognosis – 80% alive at 5 yearsOverall cure rate for ALL 30%In both AML and ALL recurrence usually within 3 years – poor prognosis. Transplant usually considered, despite the risks.
14Chronic Myeloid Leukaemia Peak age years.Slow, progressive disease. If untreated acute phase (blast crisis) leads to death rapidly.Often no symptoms in chronic phase. Symptoms often suggest blast crisis is occurring.Philadelphia chromosome associated with 95% casesFluoroscein-in-situ-Hybridisation and reverse-transcriptase PCR helps diagnosis and monitoring response to Tx
15CML: Treatment Supportive treatment as necessary Imatinib is therapy of choice in chronic phase – complete response in 95%, well tolerated, can continue indefinitelyAcute phase treated in similar way to acute leukaemias to try and return to second chronic phase.Stem cell transplant cures 75% where imatinib fails
16Chronic Lymphocytic Leukaemia Commonest leukaemia, presents mostly >65 yearsMostly asymptomatic incidental findingMedian survival approx 10 yearsDiagnosis depends on lymphocyte count >5x 109/LClinical course is variable, difficult to determine prognosis
17CLL: ManagementMajor decision is when to treat – 1/3 never need interventionRai and Binet systems use presence of symptoms and results of investigations to stage – helps determine when to treatTreatment (intermittent chemo) can help the symptoms and signs, effect on life expectancy uncertain.Supportive treatments as above are importantStem cell transplant benefits under Ix in younger patientsCLL can undergo lymphomatous (Richter’s) transformation (7%) – survival is short.
19Lymphomas Commoner than leukaemias Abnormal proliferation of lymphoid tissue – can occur anywhere lymph tissue found (LNs, spleen, thymus, GI tract...)Classifed as Hodgkin’s or Non-Hodgkin’s depending on histology
20Hodgkin’s LymphomaRare, M:F = 1.3:1, 90% in over 16s. Peak incidence in 20sMostly involves LNsDefinition of HL is presence of Reed-Sternberg cells in lymph tissue on biopsy.
21Hodgkin’s Lymphoma: Classification Classical HL:Nodular sclerosing (70%): fibrotic bands and nodules, usually affects young adultsLymphocyte-rich HL (5%): infiltration of many small lymphocytes and R-S cells, peripheral nodes, older age.Mixed Cellularity HL (25%): M>F, associated with B symptomsLymphocyte-depleted HL: rare. Numerous R-S cells, advanced B symptoms, associated with HIV.
22HL: Signs & SymptomsLymph node enlargement (usually cervical) – painless and rubbery.Enlarged spleen/liverOthers include pruritis, fatigue, anorexia, alcohol-induced pain at affected LNs.
23HL: Investigations & Treatment LN biopsy.FBC – Hb can be normal or low. High lymphocytes. ESR raised, abnormal LFTs.CXR and CT, ? PET scanStaging by Ann Arbor classification based on number/spread affected nodes and presence of B symptoms which carry a worse prognosis. Fever, drenching night sweats, >10% weight loss in 6/12Treatment – curative intent. Chemo and site-specific radiation. Recurrence uncommon, but 2nd/3rd remissions achievable
24Non-Hodgkin’s Lymphoma 70% B cell, 30% T cellViruses including HBV, herpesvirus 8, HIV all implicatedMalignant proliferation of lymphocytesSigns and Symptoms: painless superficial LN enlargement, systemic B symptoms. Extra-nodal involvement inc GIT, lung, brain, testes, thyroid, skin...Ix – FBC to look for bone marrow infiltration, ESR raised, U&Es (big nodes obstruct ureters), LFTs, CXR, CT, Bone Marrow Bx, trephine Bx, LN Bx
25NHL: TypesFollicular Lymphoma: painless lymphadenopathy. Remitting/relapsing over ~10 years. Treatment: chemo-immunotherapy, radiotherapy and occasioanlly stem cell transplant. High risk transformation to diffuse large B cell lymphomaLymphoplasmacytic lymphoma: uncommon. Extensive marrow infiltration. Management can be expectant, supportive or chemotx. Survival ~4 yearsDiffuse large B cell lymphoma: commonest. Without Tx fatal in months. >50% younger pts cured. Rapid infiltration of other organs, treated with chemoimmunotherapy.Burkitt’s lymphoma – endemic to Africa. Rapid progression. 30% have meningitis at presentation. 60% cure with chemo.
27Multiple Myeloma Malignancy of plasma (B!) cells within bone marrow Clonal expansion of abnormal proliferative plasma cells paraproteinaemia and excretion of light chains in urine (Bence Jones protein)Disease of elderly, commoner in men
28Multiple Myeloma Features C alciumR enal failureA naemiaB one problemsIf you see back pain and renal failure, think MYELOMABone destruction (vertebral or long bones, can cord compression). Pain and/or pathological fracturesHypercalcaemiaBone marrow infiltration (anaemia, neutropenia, thrombocytopenia)Renal impairment from light chain deposition in tubulesRecurrent infections (healthy immunoglobulins reduced)
31Multiple Myeloma: Treatment Survival is 5-10 years if treatment of complications is successful. Chemo and steroidsThere is no ‘cure’ for multiple myelomaSupportive therapy as beforeOrthopaedic involvement in pathological fractures
32Conclusion Haematological malignancies are COMPLICATED Lots of overlap Symptoms are non-specific and often insidiousEasier to learn if you break it down into different classifications