Common Haematological Malignancies Clare Kettlewell GPST1.

Objectives Curriculum requirements Referral pathways Common haematological malignancies – the basics. Case discussion.

Curriculum Requirements Recognise cancer illness in its early stages. Knowledge of the epidemiology of major cancers along with risk factors and unhealthy behaviours. Knowledge of referral guidelines and protocols, both local and national. Knowledge of the appropriate investigations of patients with cancer and of how they fit in with national guidelines. The ability to communicate effectively with the patient and carer(s) regarding difficult information about the disease, its treatment or its prognosis.

The 20 most commonly diagnosed cancers, UK, 2005.

Referral Guidelines for suspected haematological cancers. Primary healthcare professionals should be aware that haematological cancers can present with a variety of symptoms that may have a number of different clinical explanations. A patient who presents with symptoms suggesting haematological cancer should be referred to a team specialising in the management of haematological cancer, depending on local arrangements.

Referral Guidelines for suspected haematological cancers. Combinations of the following symptoms and signs may suggest haematological cancer and warrant full examination, further investigation (including a blood count and film) and possible referral: • fatigue • drenching night sweats • fever • weight loss • generalised itching • breathlessness • bruising • bleeding • recurrent infections • bone pain • alcohol-induced pain • abdominal pain • lymphadenopathy • splenomegaly. The urgency of referral depends on the severity of the symptoms and signs, and findings of investigations.

Referral Guidelines for suspected haematological cancers. Investigation of patients with persistent unexplained fatigue should include a full blood count, blood film and ESR, plasma viscosity or CRP (according to local policy), and repeated at least once if the patient’s condition remains unexplained and does not improve. The same investigations should be performed in patients with unexplained lymphadenopathy.

Referral Guidelines for suspected haematological cancers. Any of the following additional features of lymphadenopathy should trigger further investigation and/or referral: • persistence for 6 weeks or more • lymph nodes increasing in size • lymph nodes greater than 2 cm in size • widespread nature • associated splenomegaly, night sweats or weight loss.

Referral Guidelines for suspected haematological cancers. Investigation of a patient with unexplained bruising, bleeding, and purpura or symptoms suggesting anaemia should include a full blood count, blood film, clotting screen and erythrocyte sedimentation rate, plasma viscosity or C-reactive protein (according to local policy). A patient with bone pain that is persistent and unexplained should be investigated with full blood count and X-ray, urea and electrolytes, liver and bone profile, PSA test (in males) and erythrocyte sedimentation rate, plasma viscosity or C-reactive protein (according to local policy).

Common Haematological Cancers Acute lymphoblastic leukaemia Acute myeloid leukaemia Chronic myeloid leukaemia Chronic lymphocytic leukaemia Hodgkins lymphoma Non Hodgkins lymphoma Myeloma

Acute lymphoblastic leukaemia (ALL) Malignancy of lymphoid cells with uncontrolled proliferation of blast cells. Genetic susceptibility and environmental trigger. Associated with Downs Syndrome. Commonest cancer of childhood, rare in adults. Signs/symptoms – Marrow failure (pancytopenia) leading to anaemia, infection and bleeding. Hepato/splenomegaly. CNS infiltration (meningism, nerve palsies) Investigation – FBC, blood film, CXR/CT, LP. Treatment – Supportive (transfusion,antibiotics), chemotherapy (often intrathecal), allogenic marrow transplant. Prognosis – cure rates for children 70-90%, adults ~ 40%.

Acute myeloid leukaemia (AML) Neoplastic proliferation of blast cells derived from marrow myeloid elements. Commonest acute leukaemia of adults (1/10,000/year) Associated with radiation and Downs Syndrome. Symptoms – marrow failure, infiltration (gum hypertrophy, CNS involvement at presentation rare.) Investigation – FBC and film, bone marrow aspirate with immunophenotyping. Treatment – supportive (walking exercises can relieve fatigue), chemotherapy (intensive, long periods of immunosuppression) bone marrow transplant. Prognosis – Death in ~ 2 months if left untreated. - After treatment ~ 20% 3 yr survival.

Acute myeloid leukaemia (AML)

Chronic myeloid leukaemia (CML) Uncontrolled clonal proliferation of myeloid cells. Associated with Philadelphia chromosome ( present in >80%) Symptoms/Signs – chronic and insiduous – weight loss, fever, fatigue, sweats , gout, bleeding (platelet dysfunction), abdominal discomfort (splenomegaly >75%, often massive) Around 30% detected by chance on routine FBC. Investigations – WCC ↑, Hb low or normal. Bone marrow diagnosis. Treatment – Chemotherapy (imatinib- >90% response rate), allogenic transplant only hope of long term survival. Prognosis – Median survival 5-6 years.

Chronic lymphocytic leukaemia (CLL) Accumulation of mature B cells. Commonest leukaemia (~4/100000/year) Symptoms/signs – often none, found on routine FBC. May have enlarged rubbery non tender lymphadenopathy, hepato/spleomegaly, systemic symptoms. Investigations – increased lymphocytes, later autoimmune haemolysis and pancytopenia. Treatment – monitoring, chemotherapy only indicated if symptomatic/specific genetic mutations, radiotherapy to enlarged nodes. Prognosis – 1/3 never progress, 1/3 progress in time and 1/3 are actively progressing.

Chronic lymphocytic leukaemia (CLL)

Hodgkins Lymphoma Malignant proliferation of lymphocytes. Reed – Sternberg cells. Two peaks of incidence, young adults and elderly. Increased risk – affected sibling, EBV, SLE, post transplantation, westernisation, obesity. Symptoms/Signs – enlarged non tender lymphadenopathy. ‘B’ symptoms (weight loss, fever, night sweats), other systemic symptoms (lethargy, pruritus) SVCO emergency presentation (mediastinal involvement) Investigation - FBC, ESR, LFTs, LDH, lymph node biopsy, CT for staging (Ann Arbor system) Treatment – chemotherapy, radiotherapy or both. Prognosis – depends on stage and grade: 1a - >95% 4b - <40%

Non Hodgkins Lymphoma All lymphomas without Reed Sternberg cells. Overall incidence doubled since 1970 – (1:10,000) Causes – immunodeficiency (congenital/acquired), infection (EBV, H.Pylori) environmental toxins. Signs and symptoms – nodal disease, extranodal disease (oropharynx, skin, bone, gut, CNS, lung), systemic upset, pancytopenia due to marrow involvement. Investigations – FBC, U&Es, LFTs, LDH (increased = worse prognosis), lymph node biopsy, CT for staging (Ann Arbor) Treatment – dependent on disease subtype (basically chemotherapy +/- steroids) Prognosis – dependent on histology. Worse if age>60, systemic symptoms, bulky disease, increased LDH.

Myeloma Malignant clonal proliferation of B lymphocyte derived plasma cells. Incidence 5/100,000, peak age 70 years. Symptoms /signs: - osteolytic bone lesions – backache, pathological fractures. - Hypercalcaemia - Anaemia, thrombocytopenia, neutopenia - Recurrent bacterial infections - Renal impairment (light chain deposition) - Can present acutely with SCC, hyperviscocity, ARF. Investigation – check serum electrophoresis and ESR in all patients over 50 with back pain, xrays (punched out lesions, pepperpot skull), bone marow biopsy. Treatment – supportive (analgesia, bisphosphonates, vertebroplasty, fluids, dialysis), chemotherapy. Prognosis – median survival 3-4 years, death usually due to infection or renal failure.

Myeloma

Case Discussion

References NICE: CG27 – Referral Guideline for suspected cancer, Full Guideline. 14 July 2005. Oxford Handbook of Clinical Medicine 8th Edition. www.cancerresearch .org.uk