Haematological Malignancies - Part 3 PDF

Haematological Malignancies – Part 3 Chronic Myeloid Leukaemia (CML) Dr Ross Pallett HCPC Biomedical Scientist: BS71638 [email protected]  Preparation For this lecture you’ll need… Listened to lectures on Have something to look H...

Haematological Malignancies – Part 3 Chronic Myeloid Leukaemia (CML) Dr Ross Pallett HCPC Biomedical Scientist: BS71638 [email protected]  Preparation For this lecture you’ll need… Listened to lectures on Have something to look Haemopoiesis AML and ALL forward to on the weekend  Aim and Objectives Aim Introduce you to the pathology of chronic leukaemia Following this lecture you should be able to: 1. Classify the chronic leukaemia’s 2. Describe their clinical features 3. Laboratory diagnosis 4. Treatment  Leukaemia Classification Leukaemia is the most common type of white cell malignancy Accumulation of malignant white cells in the bone marrow or blood Malignant cells can arise from haemopoietic stem cell or progenitor Children & Adults Adults Leukaemia Rapid onset Slow onset Symptoms Subclinical/Incidental Immature cells Acute Chronic More mature cells Aggressive treatment Generally controllable Acute Chronic Acute Myeloid Chronic Myeloid Lymphoblastic Lymphocytic Leukaemia (AML) Leukaemia (CML) Leukaemia (ALL) Leukaemia (CLL) 3. Chronic Myeloid Leukaemia (CML)  Chronic Myeloid Leukaemia (CML) - Introduction Slower rate of progression compared to AML 15-20% of all leukaemias Acquired genetic change in a single pluripotent stem cell CML Massive overproduction of myeloid Chronic phase, accelerated precursors and mature effector phase and blast phase cells  CML – Philadelphia Chromosome Philadelphia chromosome – diagnostic! Translocation between chromosome 9 and 22 t(9;22)(q34;q11) Oncogene Ableson leukaemia virus ABL on chromosome 9 transferred to breakpoint cluster region (BCR) on chromosome 22 BCR-ABL fusion gene – fusion protein Constitutive tyrosine kinase activity – activation of genes involved in cell division, inhibits DNA repair and impairment of apoptosis  CML - Symptoms Typically asymptomatic – chronic phase 61 year old female presents to her GP Weight loss Raised metabolism Splenomegaly Neutrophil sequestration in the spleen Pallor Anaemia  CML – Laboratory Diagnosis 1. FBC Parameter Result Reference Range Haemoglobin 94 120-170 g/L Anaemia Red Cell Count 3.7 3.5-4.5 x 1012/L Platelets 119 150-450 x 109/L Hyperleukocytosis White Cell Count 21 3.0-11.0 x 109/L Normal platelet count Neutrophils 12 2.0-7.5 x 109/L Neutrophilia Lymphocytes 2.0 1.5-4.0 x 109/L Basophilia Monocytes 6.0 0.2-0.8 x 109/L Eosinophils 0.8 0-0.4 x 109/L Eosinophilia (sometimes) Basophils 0.2 0.01 x 109/L  CML – Laboratory Diagnosis 2. Peripheral Blood Film Myeloid precursors (1) Blast cell (2) Band Cell (3) Band cell (4) Dysplastic cell (5) Metamyelocyte  CML – Laboratory Diagnosis 3. PCR Detect BCR-ABL1 fusion gene by RT-PCR - EDTA sample  CML – Treatment Chronic Phase Tyrosine Kinase Inhibitors (TKIs) o Effectiveness monitored by bone marrow karyotyping and blood and bone marrow BCR-ABL1 PCR o Resistance? Stem Cell Transplant Allogenic – Only curative treatment for CML  Lecture Summary CML is a clonal malignancy of an acquired genetic change in a pluripotent stem cell Hallmark of the disease is the Philadelphia chromosome (t(9;22)) and the chimeric BCR-ABL1 fusion protein with tyrosine kinase activity Often asymptomatic until progression to the accelerated phase of the disease Diagnosis based on FBC, blood film, bone marrow examination, PCR and cytogenetics First line treatment is typically in the form of tyrosine kinase inhibitors Stem cell transplantation can be curative Haematological Malignancies – Part 4 Chronic Lymphocytic Leukaemia (CLL) Dr Ross Pallett HCPC Biomedical Scientist: BS71638 [email protected]  Preparation For this lecture you’ll need… Listened to CML lecture Immunology 101 Chocolate Chip Cookies  Leukaemia Classification Children & Adults Adults Leukaemia Rapid onset Slow onset Symptoms Subclinical/Incidental Immature cells Acute Chronic More mature cells Aggressive treatment Generally controllable Acute Chronic Acute Myeloid Chronic Myeloid Lymphoblastic Lymphocytic Leukaemia (AML) Leukaemia (CML) Leukaemia (ALL) Leukaemia (CLL)  Chronic Lymphocytic Leukaemia (CLL) - Introduction Most common leukaemia Clonal proliferation of small in the West mature B cells found in the blood Divided into unmutated and mutated Ig Chronic relapses heavy chain variable region (IGHV)  Classification of CLL As seen with ALL - important for determining whether to commence treatment and to determine prognosis Binet staging classification Criteria Life Expectancy Stage A No anaemia or thrombocytopenia 13 years 3 lymphoid areas enlarged Stage C Anaemia and/or 2 years thrombocytopenia Sites of lymphoid organs: cervical, axillary and inguinal nodes, the spleen and the liver  CLL - Symptoms 77 year old male presents to his GP complaining of fatigue and a swollen abdomen Lethargy and pallor Recurrent infections Bruising Splenomegaly Lymphadenopathy  CLL – Laboratory Diagnosis 1. FBC Parameter Result Reference Range Haemoglobin 120 120-170 g/L Thrombocytopenia Red Cell Count 3.4 3.5-4.5 x 1012/L Hyperleukocytosis Platelets 139 150-450 x 109/L White Cell Count 32.7 3.0-11.0 x 109/L Lymphocytosis Neutrophils 4 2.0-7.5 x 109/L Lymphocytes 26 1.5-4.0 x 109/L Monocytes 2 0.2-0.8 x 109/L Eosinophils 0.3 0-0.4 x 109/L Basophils 0.4 0-0.1 x 109/L  CLL – Laboratory Diagnosis 2. Peripheral Blood Film Small lymphocytes Smudge cells  CLL – Laboratory Diagnosis 4. Immunophenotyping Markers CD19 smIg CD5 CD20 CD23 FMC7  CLL – Laboratory Diagnosis 6. Additional Tests Biochemistry Low antibody levels Cytogenetics e.g. del13q14, ZAP-70 DAT Autoantibodies against erythrocytes  CLL – Treatment Rituximab + Chemotherapy Begin when symptoms become significant Rituximab (anti-CD20), fludarabine and cyclophosphamide Corticosteroids Aid recovery from pancytopenia Splenectomy Reduce pain and in patients who do not respond to steroids Immunoglobulin replacement Well tolerated and improve quality of life  Lecture Summary Most common leukaemia in the Western world Clonal proliferation of B-lymphocytes Symptoms include anaemia, recurrent infections, weight loss, lymphadenopathy and hepatosplenomegaly Diagnosis includes FBC, blood film, bone marrow biopsy and immunophenotyping Best prognosis is the stage of the disease Chemotherapy is not often immediately needed in early CLL