Multiple Myeloma Presentation PDF

1 Multiple Myeloma Dr. Halah Awadallah 7 February December 22, 2024 2011  2 7 February 2011 Multiple myeloma is a B-cell malignancy cha...

1 Multiple Myeloma Dr. Halah Awadallah 7 February December 22, 2024 2011  2 7 February 2011 Multiple myeloma is a B-cell malignancy characterized by a monoclonal expansion and accumulation of abnormal plasma cells in the bone marrow. Myeloma belongs to a group of disorders called plasma cell dyscrasias.  3 7 February 2011 Myeloma constitutes 1% of all cancers, but it is the second most common blood cancer after lymphomas and accounts for 10% of haematological malignancies. The median age at diagnosis is 60–65 years. Fewer than 2% of myeloma patients are under 40 years. Men are more affected than women. It is more common in African and Caribbean populations.  4 7 February 2011 Pathogenesis Multiple myeloma is a malignant condition caused by clonal proliferation of plasma cells. These plasma cells are usually confined to the bone marrow but may be seen in the peripheral blood in end-stage myeloma.  5 7 February 2011 The cause of myeloma is unknown, but Exposure to chemicals and radiation may be associated with the development of myeloma in predisposed individuals. Studies have suggested a link between myeloma and herpes virus infections (especially herpes virus 8), Epstein– Barr virus, human immunodeficiency virus & hepatitis viruses.  6 Role of bone marrow 7 February 2011 stroma: The multiple interactions between myeloma, stromal and endothelial cells and osteoclasts reflect the vital role of the bone marrow microenvironment in the biology of the disease. The production of different cytokines by both stromal and myeloma cells enhances myeloma proliferation and growth, osteoclast activation and vessel formation. The inhibition of T-lymphocytes, increases the immunodeficiency in myeloma. Suppression of osteoblasts in combination with osteoclast activation leads to bone loss.  7 7 February 2011  8 7 February 2011 Clinical features Plasma cell infiltration of bone marrow results in bone marrow failure and bone lesions. Patients present with symptoms due to: Bone disease; Hypercalcaemia; Impaired haemopoiesis; Immune paresis; Renal failure.  9 7 February Bone disease 2011 Bone destruction in myeloma is related to increased osteoclastic activity which is not accompanied by a comparable increase in osteoblast formation. This uncoupling of resorption and formation leads to rapid bone loss, osteoporosis, lytic lesions and fractures. Bone pain is the most common symptom (75%) and results from osteolytic lesions and pathological fractures – mainly wedging or collapse of vertebral bodies with or without osteoporosis. kyphosis and loss of height may occur from vertebral compression fractures.  10 7 February 2011 Osteolytic lesions in the skull and humerus bone  11 7 February 2011 Immune paresis Many patients with multiple myeloma have reduced serum levels of normal immunoglobulins which make them susceptible to bacterial infections. Immune paresis, renal failure, neutropenia and anti- myeloma therapy can combine to cause severe immunodeficiency, and infections are a major cause of death in these patients.  12 7 February 2011 Normochromic, normocytic anaemia may be presenting feature at diagnosis. It may be due to: The infiltration of the bone marrow by myeloma cells; Chronic inflammation; The use of cytotoxic drugs.  Thrombocytopenia and neutropenia may also occur due to bone marrow infiltration or due to use of chemotherapy.  13 7 February 2011 Hypercalcaemia Hypercalcaemia occurs in 45% of Pts. It is due to imbalance between bone formation and bone destruction. Hypercalcaemia may be severe enough to cause life- threatening dehydration and renal failure.  14 7 February 2011 Nephropathy: Renal dysfunction occurs when the tubular absorptive capacity of light chains is exhausted, resulting in renal damage. Other causes of renal dysfunction are: Hypercalcaemia with hypercalciuria; Amyloid light chain (AL) amyloidosis associated with λ-light-chain disease; Immunoglobulin light-chain deposition; Infection; Hyperuricaemia Anti-inflammatory drugs use.  15 7 February 2011 Laboratory diagnosis: Full blood count, film and ESR Bone marrow examination Evaluation of kidney function, serum calcium, CRP, β2-microglobulin, LDH, uric acid levels and liver function tests. Protein electrophoresis. Quantitative analysis of the normal immunoglobulins Bence Jones protein excretion  16 7 February 2011 CBC: There is usually normocytic normochromic anaemia ; Rouleaux formation is marked in most cases; Neutropaenia and thrombocytopaenia in advanced disease; Abnormal plasma cell in about 15% of Pts; High ESR.  17 7 February 2011 Bone marrow aspiration and trephine biopsy for morphology. Usually there is increased plasma cells >20% with abnormal forms.(binucleated or trinucleated)  19 7 February 2011 A complete skeletal survey. In most patients with myeloma, the malignant plasma cells secrete an abnormal immunoglobulin (paraprotein), but around 1% of patients have non- secretory disease. Suppression of the normal immunoglobulins is a typical finding in most cases.  20 7 February 2011 A complete skeletal survey. In most patients with myeloma, the malignant plasma cells secrete an abnormal immunoglobulin (paraprotein), but around 1% of patients have non- secretory disease. Nearly 60% have detectable IgG paraprotein, 20% have IgA , 15–20% light-chain only, and less than 1% have IgD or IgE paraprotein. Suppression of the normal immunoglobulins is a typical finding in most cases. Serum protein electrophoresis in MM showing abnormal paraprotein 7 February 2011 21  22 7 February 2011 Staging and prognosis Salmon–Durie staging system is the standard system for staging a myeloma patient. Stage I: 1. Haemoglobin > 10.5 g/dL 2. Serum calcium normal 3. X-rays normal bone structure or solitary plasmocytoma 4. Low paraprotein levels - IgG < 50 g/L - IgA < 30 g/L 5. Urinary light chain < 4 g/24 h  23 7 February 2011 Stage III:- One or more of the following 1. Haemoglobin < 8.5 g/dL 2. Serum calcium > 3 mmol/L 3. Advanced lytic bone lesions (> three lytic lesions) 4. High paraprotein levels - IgG > 70/L - IgA > 50 g/L 5. Urinary light chain > 12 g/24 h  24 7 February 2011 Stage II:- Fitting neither stage I nor stage III. Subclassification: A. Serum creatinine < 170 μmol/L B. Serum creatinine ≥ 170 μmol/L  25 7 February 2011 Prognosis: A number of prognostic indices have been proposed: 1. β2-microglobulin is the most powerful prognostic marker, 2. While CRP, albumin, LDH, and chromosome 13q loss have prognostic values. Only two parameters, are now used: β2-microglobulin and serum albumin.  26 7 February 2011 Treatment: Patients with no symptoms, normal renal function and absence of bone lesions, classified as stage 1 may remain stable for a long time (2-3yrs) without any chemotherapy. Follow up is necessary. They account for about 20% of myeloma patients.  27 7 February 2011  Supportive therapy: ▫ Analgesia ▫ Hydration ▫ Treatment of hypercalcaemia ▫ Treatment of renal impairment ▫ Treatment of any infection ▫ Local radiotherapy if required. ▫ Decompression laminectomy in cord compression. ▫ Blood products.  28 7 February 2011 Conventional chemotherapy Conventional doses of chemotherapy rarely result in complete remission (CR) and cure is not always achieved. Initial chemotherapy can be: Melphalan and prednisolone (MP), A plateau phase- is reached when no response to further doses Maintenance therapy by Interferon-alpha. Unfortunately, most patients die from their disease.  29 7 February 2011 THANKS