Case Study Multiple Myeloma

Amy 54 year old female One year history of :- Fatigue shortness of breath, and dizziness Weight loss Increasingly severe back pain. Bone fractures Skin lesions Enlarged tongue Infections

Amy wented to the doctor, and make physical examination:- - She appeared pale - but otherwise her physical exam was within normal limits

Asked the doctor several tests include :-

Aspirate differential . CBC Bone marrow biopsy: Aspirate differential . Chemistry: Total protein . Serum protein electrophoresis . Immunoglobulins, quantitative Radiography

Parameters Result Normal Rang Observation RBC 2.85 x1012/L 4.7 to 6.1 x 1012/L low HB 7.6 g/dL 13.0-18.0 g/dL Low HCT 23.9 % 40-52 % MCV 83.8 fl 80-97 fl Normal MCH 26.7 pg 27-31 pg Low -nearly normal MCHC 31.8 g/dL 32-36 % Low –nearly normal RDW 16.8 13 ± 1.5 % high WBC 8.4 x109/L 4,5-11 x 109/L normal N 60 % 40-75% L 26 % 20-45% M 12 % 2-10% E 1 % 1-6% B 0-1% PLT 418 x 109/L 150 - 400 x 109/L High - near normal

calcium >11.5 mg/dL high Chemistry Observation Parameters high AlT AST High >2 mg/dL creatinine Uric acid calcium >11.5 mg/dL high HyperCalcemia

Chemistry Observation Normal Rang Result Parameters high 5.2-8.3 g/dL Total protein low 3.0-5.0 g/dL 2.8 g/dL Albumin normal 0.1-0.5 g/dL 0.4 g/dL Alpha1 Globulins 0.5-1.2 g/dL 1.0 g/dL Alpha2 Globulins 0.5-1.1 g/dL 0.8 g/dL Beta Globulins 0.6-1.7 g/dL 5.6 g/dL Gamma Globulins

Immunoglobulins, quantitative Observation Normal Rang Result Parameters seen in gamma fraction 5.5 g/dL Monoclonal protein low 85-450 mg/dL 9 mg/dL IgA high 800-1700 mg/dL 5800 mg/dL IgG 60-370 mg/dL 25 mg/dL IgM

Bone marrow biopsy: Aspirate differential Eccentric : ليست في المركز

Radiography: Multiple lytic lesions of the skull, spine, pelvis, and femurs.

Question What is the most likely diagnosis?

Multiple myeloma (IgG, kappa type)

Discussion : Anemia occurs when the red blood cell count is low. It can cause fatigue, shortness of breath, and dizziness. Bone loss from myeloma causes an excess of calcium to be released into the bloodstream, Hypercalcemia can also be caused by overactive parathyroid glands. Excess protein and calcium in the blood put a strain on the kidneys as they try to keep up with filtering all of the unwanted material out of the blood. The kidneys try to process all of the calcium and protein, but they can’t, and they get overworked. If the kidneys are overworked for too long, kidney failure occurs. raised serum creatinine due to reduced kidney function,

Uric acid levels may be elevated as a complication of multiple myeloma Uric acid levels may be elevated as a complication of multiple myeloma. Serum viscosity, a measure of how "thick" the fluid portion of the blood is; when levels of the abnormal protein become very high, serum viscosity may increase and cause symptoms. ↑ M protein in serum, may have ↓ levels of normal antibodies A monoclonal protein M spike β2-microglobulin ↑ Levels (measure of tumor burden) Staging is an evaluation of how much abnormal immunoglobulin is being produced, how much calcium is in the blood, how extensive and severe the bone damage is, and how anemic the affected person is. Staging helps to determine a person's prognosis.

Clinical Course : The patient was treated with chemotherapy and radiation therapy. Her bone pain lessened, and her serum protein levels gradually decreased to within normal ranges. After several months, however, she was again experiencing bone pain and abnormal protein levels. She continued to be followed in Hematology Clinic, and at her last visit--four years after the original diagnosis--the disease still appeared to be progressing slowly.

Multiple Myeloma: Abnormal Proliferation of Malignant Plasma Cells Angiogenesis : تكوين الاوعية .

Epidemiology Second most common hematological malignancy. Incidence and rates : 1% of all cancers. US incidence: 19,900 new cases per year. US prevalence: 100,000 patients. Deaths: estimated 10,790 per year. More than 80% of affected patients >age 60. Affects slightly more men than women (1.6:1).

Clinical Manifestations of Multiple Myeloma Over proliferation of plasma cells can cause : Risk of infection Osteolytic bone lesions Hypercalcemia Bone marrow suppression (pancytopenia) Renal complication risk

2- Production of monoclonal M proteins causes : Decreased levels of normal immunoglobulins Hyperviscosity

Major Symptoms at Diagnosis Bone pain - 58% Fatigue - 32% Weight loss - 24% Asymptomatic - 11%

Common Sites for Bone Involvement Skull Spine : Thoracic Lumbar Vertebrae Pelvis Long bones Spinal cord : - compression can occur 23

Diagnostic Evaluation of Multiple Myeloma Test Finding (s) With Myeloma CBC with differential counts ↓ Hgb, ↓ WBC, ↓ platelets Electrolytes ↑ Creat, ↑ Ca+, ↑ Uric acid, ↓ Alb Serum electrophoresis with quantitative immunoglobulins ↑ M protein in serum, may have ↓ levels of normal antibodies Immunofixation Identifies light/heavy chain types M protein β2-microglobulin ↑ Levels (measure of tumor burden) 24-hour urine protein electrophoresis ↑ Monoclonal protein (Bence Jones) Bone marrow biopsy ≥ 10% plasma cells Skeletal imaging Osteolytic lesions, osteoporosis Serum free light chain ↑ Free light chains MRI Evaluation of involvement of disease The early stages of multiple myeloma are often asymptomatic and the disease may be discovered on routine laboratory testing When myeloma is suspected (ie, older patients with unexplained pain, fracture, anemia), the diagnostic evaluation should include: Laboratory tests of both serum and urine Radiographic imaging Bone marrow biopsy The alterations associated with myeloma are listed here Quantitative immunoglobulins measure the antibodies IgG, IgA, IgM, IgE, and IgD with normal ranges: (IgG 650-1500 mg/dL; IgA (76-390 mg/dL; IgM 40-345 mg/dL; IgE 0-380 IU/ml) Beta 2 microglobulin is a standard measure of tumor burden for myeloma (normal range, 2.0–2.5 µg/mL) C-reactive protein is a surrogate marker for IL-6, a growth factor for myeloma cells A 24-hour urine protein electrophoresis (UPEP) measures the presence and amount of myeloma protein in the urine A serum-based assay (Freelite™) detects and quantifies free light chains, which may help predict the risk of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma. This test is also easier for patients to complete than a 24-hour urine collection. Emerging evidence suggests that use of magnetic resonance imaging (MRI) is more sensitive and specific than x-ray and scintigraphy for detecting bone metastases in multiple myeloma patients. Thus, MRI may also be used for initial assessment of multiple myeloma. Alb = albumin; Creat = creatinine; Hgb = hemoglobin; MRI = magnetic resonance imaging .

Stem cell transplantation: MM Treatment Options Conventional chemotherapy: Melphalan Doxorubicin Cyclophosphamide Steroid therapy: Dexamethasone Prednisone Stem cell transplantation: Autologous Allogenic Radiation therapy

Prepration : Presentation : Asmaa Ashour Noor Al-Safadi Areej Abuzubaida Nermeen Al-Ashi