Heme Malignancies 2025 PDF

HEMATOLOGIC MALIGNANCIES Medical Practice Spring 2025 Dr. Tom Hatten, DO Objectives: HEM1.1-1.10 Hematologic Malignancies Acute/Chronic Lymphocytic Leukemia (ALL/CLL) Acute/Chronic Myelogenous Leukemia (AML/CML) Leukopenia Lymphoma (Hodgk...

HEMATOLOGIC MALIGNANCIES Medical Practice Spring 2025 Dr. Tom Hatten, DO Objectives: HEM1.1-1.10 Hematologic Malignancies Acute/Chronic Lymphocytic Leukemia (ALL/CLL) Acute/Chronic Myelogenous Leukemia (AML/CML) Leukopenia Lymphoma (Hodgkin and non-Hodgkin) Multiple Myeloma Myelodysplasia LEUKEMIA Leukemia is a malignancy of the blood-forming tissues characterized by a large increase in the numbers of white blood cells (leukocytes) in the circulation or bone marrow. Caused by disruptions in the normal cell regulatory process that leads to uncontrolled proliferation of hematopoietic stem cells in bone marrow. The four general leukemia subtypes are: Acute Lymphoblastic leukemia (ALL)…aka Acute Lymphocytic Leukemia Acute Myelogenous Leukemia (AML) Chronic Lymphocytic Leukemia (CLL) Chronic Myelogenous Leukemia (CML) LYMPHOMA A heterogeneous group of malignant neoplasms of lymphocytes, which can involve lymphatic tissue, bone marrow, or extranodal sites. The World Health Organization’s classification system identifies more than 90 different lymphoma subtypes. The initial stratification is derived from B-cell, T-cell or natural killer cell origin. Hodgkin lymphoma (HL) refers to lymphoid neoplasms in which distinctive malignant lymphoid cells (Hodgkin/Reed-Sternberg cells) are admixed with a much larger population of non-neoplastic inflammatory cells and/or fibrosis. Non-Hodgkin lymphoma (NHL) consists of a diverse group of malignant tumors of the lymphoid tissues variously derived from the clonal expansion of B cells, T cells, natural killer (NK) cells or precursors of these cells. Leukopenia/Neutropenia Leukopenia – Reduced total WBC count (50% have one or more symptoms) ▪ Lymphadenopathy (~50%) ▪ MSK/Bone pain (21-38%) – limp or refusal to bear weight in young children ▪ Fever ▪ Pallor, fatigue (manifestations of anemia) ▪ Bleeding or bruising (manifestations of thrombocytopenia) ▪ Frequent headaches ( 20% of total cellularity of the bone marrow biopsy Auer Rods in a myeloid blast cell MANAGEMENT ▪ Remission Induction ▪ Intensive combination therapy given with goal of achieving a complete remission by rapidly reducing # of leukemia cells and restoring normal bone marrow function ▪ Post Remission Therapy- ▪ Consolidation – intense and immediately follows above ▪ Chemotherapy vs. hematopoietic cell transplantation (often called a stem cell transplantation) ▪ Maintenance – non-myelosuppressive treatment with chemo or targeted therapeutic agent for months to years ▪ Depends on type of AML PROGNOSIS ▪ Adults: ▪ Depends on cytogenetic and molecular features ▪ Indicators of poor prognosis: ▪ Advancing age ▪ Poor performance status (see next slide) ▪ History of prior exposure to cytotoxic agents or chemotherapy ▪ History of prior Myelodysplastic syndrome. ▪ Children: ▪ Overall survival is 65-70% ▪ Approximately 30% will experience relapse COMPLICATIONS: ▪ Hyperleukocytosis (WBC >50,000-100,000) ▪ A MEDICAL EMERGENCY ▪ Is associated with the following…. ▪ Leukostasis – hemorrhagic or thromboembolic organ damage from the elevated WBCs ▪ Treatment: leukapheresis ▪ Tumor lysis syndrome – lysis of large amounts of leukemic cells results in massive elevations in potassium, phosphate and nucleic acids (more than 25% increase over baseline.) Causes an increase in uric acid and can result in acute kidney injury (AKI) ▪ Treatment: hyperhydration (best treatment is prevention with allopurinol) ▪ DIC – hemorrhage and microvascular thrombosis that can lead to end-organ damage ▪ Prominent in APL (acute promyelocytic leukemia) ▪ Treatment: ATRA (all-trans retinoic acid) CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) ▪ Is a mature B cell neoplasm characterized by a progressive accumulation of monoclonal B lymphocytes. ▪ Grouped as chronic lymphocytic leukemia/small lymphocytic lymphoma (non Hodgkin lymphoma) ▪ Identical pathologic & immunophenotypic features; difference is in where they primarily manifest ▪ Malignant clonal disorder of B lymphocytes ▪ Indolent (slow growing, not immediately problematic), progressive accumulation of functionally incompetent lymphocytes EPIDEMIOLOGY ▪ The most common leukemia in adults in Western countries ▪ 25-30% of all leukemias in US ▪ Men>Women ▪ 90% of cases occurring after age 50 years ▪ Median age at presentation = 70 years ▪ In the US, higher incidence among White Americans RISK FACTORS ▪ No clear environmental/occupational risk factors ▪ Family hx of CLL/SLL SYMPTOMS ▪ Painless swelling of lymph nodes (often cervical) ▪ Typical “B” symptoms: ▪ Unintentional weight loss >/= 10% of body weight within previous 6 months ▪ Fevers > 100.5 for >/= 2 weeks without evidence of infection ▪ Drenching night sweats ▪ Extreme fatigue SIGNS ▪ Lymphadenopathy (50-90%) ▪ Firm, rounded, discrete, nontender, and freely mobile upon palpation ▪ MC cervical, supraclavicular, and axillary ▪ Splenomegaly (25-55%) ▪ Hepatomegaly (15-25%) ▪ Leukemia cutis ▪ Most often affects the face DIAGNOSTICS ▪ CBC ▪ WBC with differential ▪ Elevated with absolute lymphocytosis >5000/microliter ▪ Required for the diagnosis ▪ Cytopenias: Neutropenia, Anemia, Thrombocytopenia ▪ Peripheral smear ▪ Smudge/smear cells present ▪ Bone marrow aspirate and biopsy – not always required ▪ Lymph node and/or spleen biopsy ▪ Immunoglobulin abnormalities CLINICAL INTERVENTIONS ▪ Patient Education ▪ Hematology/Oncology Consultation ▪ Therapy depends on the stage ▪ CLL is an indolent disease which cannot be cured by conventional chemotherapy ▪ Current chemotherapy regimens can achieve complete remission but patients eventually relapse  CLINICAL INTERVENTIONS ▪ Early stage, asymptomatic CLL = Observation ▪ Localized stage I & maybe stage II disease = radiation to the involved field ▪ “Active”/advanced disease = chemotherapy +/- radiation ▪ Progressive marrow failure (worsening cytopenias) ▪ Massive/progressive lymphadenopathy or splenomegaly ▪ Progressive lymphocytosis (inc > 50% over 2 month period) ▪ Autoimmune anemia/thrombocytopenia unresponsive to traditional therapy ▪ Symptomatic extranodal involvement (skin, kidney, lung, spine) ▪ Constitutional symptoms – wt loss, fatigue, fever, night sweats COMPLICATIONS ▪ Chemotherapy-induced neutropenic fever ▪ Chemotherapy-induced tumor lysis syndrome CHRONIC MYELOGENOUS LEUKEMIA (CML) ▪ A myeloproliferative disorder characterized by uncontrolled production of mature and maturing granulocytes ▪ Mostly neutrophils ▪ But also basophils & eosinophils  PHILADELPHIA CHROMOSOME ▪ Characterized by a specific chromosomal abnormality and specific molecular abnormality ▪ Philadelphia chromosome is a reciprocal translocation between the long arms of chromosomes 9 and 22 EPIDEMIOLOGY ▪ 15-20% of leukemias in adults ▪ Slight male predominance ▪ Median age 50-60 yrs ▪ Only known risk factor = exposure to ionizing radiation SYMPTOMS ▪ Asymptomatic (20-50%) ▪ Fatigue (34%) ▪ Night sweats (15%) ▪ Low-grade fever ▪ Abdominal fullness (15%) ▪ Weight loss (20%) ▪ Abnormal bleeding (21%) SIGNS ▪ Splenomegaly ▪ Possibly abdominal tenderness to palpation in left upper quadrant ▪ Possibly tenderness to palpation over lower sternum ▪ Acute gouty arthritis DIAGNOSTICS ▪ Absolute leukocytosis (median of 100,000/µL) with a left shift ▪ WBC Differential – all cells of neutrophilic series ▪ “Leukemic hiatus/myelocyte bulge” = greater % myelocytes than metamyelocytes ▪ Normochromic, normocytic anemia ▪ Normal to elevated platelets Left shift: the abnormal presence of immature blood cells and their precursors in the peripheral blood, mainly neutrophils. DIAGNOSTICS ▪ Peripheral smear – leukocytosis ▪ Bone marrow biopsy – differential count key to determining disease stage ▪ Genetics – all patients will have evidence of Philadelphia chromosome on FISH, RT-PCR or karyotyping ▪ This is a CONFIRMATORY finding CLINICAL COURSE—TYPICALLY 3 PHASES: ▪ Chronic phase ▪ 85% are in the chronic phase at time of diagnosis ▪ Accelerated phase ▪ Neutrophil differentiation becomes progressively impaired ▪ Leukocyte counts more difficult to control with treatment ▪ Blasts 10-19% in peripheral blood or bone marrow ▪ Blast crisis ▪ Resembles acute leukemia ▪ Blasts > 20% of peripheral blood or bone marrow ▪ Uncontrolled proliferation TREATMENT ▪ If no treatment, will progress to terminal blast crisis ▪ Can start hydroxyurea to reduce WBC count while awaiting confirmation of dx and phase ▪ Curative = allogenic hematopoietic cell transplantation (HCT) ▪ Consider in younger patients with donor, accelerated phase and blast crisis ▪ Tyrosine kinase inhibitors – not curative, but help achieve long- term control in majority of patients (chronic phase) ▪ Imatinib, Dasatinib, Nilotinib, Bosutinib  PROGNOSIS ▪ Prognosis has improved with available treatments ▪ Generally, those diagnosed in earlier age with better prognosis ▪With treatment, the five-year survival rate for CML is around 85% in the chronic phase, but lower in the accelerated or blast phase. SUSPECT CML IN A PATIENT WITH: ▪ Systemic complaints (fatigue, malaise, sweating, weight loss) ▪ Early satiety/abdominal discomfort (due to splenomegaly) ▪ Tenderness of the lower sternum (due to an expanding bone marrow) ▪ Hepatosplenomegaly ▪ Gouty arthritis due to rising uric acid level ▪ Lab findings: ▪ Elevated WBC with smear demonstrating myelocyte bulge (more myelocytes than the more mature metamyelocytes; aka “leukemic hiatus”) ▪ Mild anemia ▪ Thrombocytosis ▪ Basophilia ▪ Confirmed with Philadelphia chromosome LYMPHOMA Hodgkin Lymphoma Non-Hodgkin Lymphoma LYMPHOMA VS LEUKEMIA ▪ Lymphoma = malignant proliferation of lymphoid cells, usually in association with and arising from lymphoid tissues (ie, lymph nodes, thymus, spleen) ▪ Leukemia = malignancy arising from the bone marrow, which may include lymphoid cells HODGKIN LYMPHOMA (HL) Classic “Owl’s Eyes” appearance of HRS cell ▪ Uncommon (10% of all lymphomas) hematologic malignancy arising from mature B cells ▪ Most commonly presents with painless cervical and/or supraclavicular lymphadenopathy in a young adult ▪ Characterized by the presence of HRS cell is a collective term for classic Reed- Sternberg cells and characteristic variant cells that Hodgkin/Reed-Sternberg (HRS) cells are referred to as Hodgkin cells. How Did Hodgkin’s Lymphoma Get Named? Hodgkin's Lymphoma is named after the physician who first described the disease, Thomas Hodgkin. In 1832, Hodgkin published a paper describing several cases of patients with enlarged lymph nodes and splenomegaly. He noted that these cases were distinct from other types of lymphomas, and that they had a characteristic type of cell, now known as the Reed-Sternberg cell, present in the lymph nodes. The disease was initially called "Hodgkin's disease" in honor of Thomas Hodgkin, and later came to be known as "Hodgkin's Lymphoma" to reflect the fact that it is a type of cancer of the lymphatic system. EPIDEMIOLOGY ▪ Bimodal age distribution ▪ First peak at ~25 years, Second peak after age 50 (usu around 65) ▪ In pediatric population = most common form of lymphoma ▪ Children have better response than adults ▪ Most cases occur 16 years + 2 MAJOR CATEGORIES OF HL: 1. Classic HL (cHL)--(90% of cases) ▪ Nodular sclerosis cHL (70 percent) ▪ Mixed cellularity cHL (20 to 25 percent) ▪ Lymphocyte rich cHL (5 percent) ▪ Lymphocyte depleted cHL (less than 1 percent) 2. Nodular lymphocyte predominant HL *Biopsy required to determine histologic subtype RISK FACTORS: ▪ EBV infection ▪ Smoking ▪ Immunosuppression ▪ Autoimmune disorders ▪ Family member with HL PRESENTATION ▪ Most common symptoms: ▪ Lymphadenopathy (80%) – painless cervical ▪ Mediastinal mass (present in ~75%) may result in dysphagia, dyspnea, wheezing, cough, stridor or superior vena cava (SVC) syndrome ▪ Almost 30% of patients greater than 12 years of age have a mass >1/3 of chest diameter ▪ May also have B symptoms ▪ Drenching night sweats ▪ Recurrent fevers >38℃ ▪ Unintentional weight loss >10% over 6 months prior to diagnosis ▪ Pruritus – 10-15% - generalized EVALUATION: ▪ Comprehensive physical examination including: ▪ Height and weight ▪ Documentation of lymphadenopathy (if present) ▪ Liver and spleen size ▪ Can have enlargement in advanced HL ▪ Skin examination ▪ Can have cutaneous manifestations ▪ Pulmonary examination ▪ ECOG performance status (determines a pt’s ability to tolerate therapies, specifically chemo, see next slide) DIAGNOSTICS ▪ Basics ▪ CBC with differential, peripheral smear, CMP, ESR, LDH, UA ▪ AP and lateral CXR ▪ *CT neck/chest/abdomen/pelvis ▪ *PET scan Tissue biopsy can be from lymph node, ▪ Bilateral bone marrow aspirates and biopsies mediastinal mass or extranodal sites identified on imaging. ▪ Definitive ▪ Requires (lymph) tissue biopsy – Reed-Sternberg cells are diagnostic ▪ Treatment of HL is primarily guided by the clinical stage of disease (determined by the Lugano classification): ▪ Stage I ▪ Stage II ▪ Stage III ▪ Stage IV ▪ Majority of pts will be cured but there are treatment-related toxicities causing late mortality. TREATMENT: ▪ Stage I to II: ▪ Usually treated with combo of chemo plus radiation ▪ Chemo alone is acceptable alternative for those with favorable disease characteristics who are at a higher risk of complications from radiation ▪ Stage III to IV: ▪ Combination chemotherapy PROGNOSIS ▪ Pediatrics – ▪ Stage I and II→ 90-95% 5 year survival ▪ Stage II - IV slightly worse, but improving ▪ Adults – ▪ Stage I and II have high likelihood of achieving long-term complete remission ▪ Use International Prognostic Score COMPLICATIONS: ▪ Gonadal dysfunction ▪ Cardiopulmonary toxicity ▪ Second malignancies ▪ Functional impairment and reduced overall general health ▪ Impaired growth of soft tissue and bones (radiation related) ▪ Thyroid dysfunction (more so radiation related) NON-HODGKIN LYMPHOMAS (NHL) ▪ Heterogeneous group of malignancies of the lymphoid system ▪ Derived from B cell progenitors, T cell progenitors, mature B cells, mature T cells, or natural killer cells ▪ In the US, more common in males and in Caucasians ▪ Incidence increases with age ▪ 5th most common diagnosis of pediatric cancer—more aggressive in peds than adults NHL VARIANTS ▪ Presentation varies tremendously depending upon the type of lymphoma and the areas of involvement ▪ Aggressive lymphomas – diffuse large B-cell lymphoma, Burkitt lymphoma, adult T-cell lymphoma and precursor B and T lymphoblastic leukemia/lymphoma ▪ Indolent – follicular, CLL/small lymphocytic lymphoma and splenic marginal zone lymphoma ▪ Diffuse large B-cell lymphoma is the most common type of lymphoma in adults RISK FACTORS IN THE ADULT ▪ Age >50 years ▪ Male gender ▪ Immunocompromised host ▪ EBV, HIV, HCV, HBV ▪ Personal or family history of lymphoma or other hematopoietic malignancy ▪ Past radiation or chemo ▪ Exposure to pesticides, hair dyes and dioxins ▪ Autoimmune disease ▪ Inflammatory GI diseases PRESENTATION Emergency symptoms Symptoms ▪ SVC or IVC compression ▪ B Symptoms (40%) ▪ Airway obstruction ▪ Enlarging, non-tender ▪ Intestinal obstruction lymphadenopathy ▪ Spinal cord compression ▪ Fever of unknown origin ▪ Pericardial tamponade ▪ Lymphomatous meningitis ▪ Tumor lysis syndrome ▪ Ureteral obstruction ▪ Venous thromboembolic disease ▪ Hypercalcemia (adult T-cell) ▪ Hyperleukocytosis PHYSICAL EXAM ▪ Isolated or diffuse lymphadenopathy ▪ May have extranodal sites of disease (ex. Skin, GI tract, CNS) EVALUATION ▪ Basics ▪ CBC, CMP, LDH, serum uric acid ▪ CT neck/chest/abdomen/pelvis ▪ PET (+/- CT) ▪ Bone marrow biopsy for staging ▪ Definitive ▪ Excisional Biopsy – REQUIRED for diagnosis ▪ Enlarged peripheral lymph nodes preferred – easily accessed and high diagnostic yield MANAGEMENT ▪ Prognosis is dependent on histopathology – ▪ Use Lanugo classification response scale ▪ Treatment ▪ Completely dependent on specific histologic subtype + clinical and pathologic prognostic factors ▪ Chemotherapy ▪ Immunotherapy ▪ Radiation therapy ▪ Combo of above COMPLICATIONS ▪ Development of second malignancies in long-term survivors ▪ Cardiovascular complications from chemo/radiation ▪ Gonadal dysfunction ▪ PTSD ▪ Progressive multifocal leukoencephalopathy ▪ If treated with rituximab MYELODYSPLASTIC SYNDROMES MYELODYSPLASTIC SYNDROME ▪ Group of hematologic malignancies ▪ Characterized by dysplastic and ineffective blood cell production, clonal hematopoiesis, and abnormal cellular maturation ▪ Anemia ▪ Neutropenia ▪ Thrombocytopenia ▪ Shares clinical and pathologic features of AML but Infections ▪ Anemia -> fatigue, weakness, exercise intolerance, angina, dizziness, etc PHYSICAL DIAGNOSIS ▪ Pallor (60%) ▪ Petechiae/Purpura (26%) ▪ Hepatomegaly, Splenomegaly, lymphadenopathy = UNCOMMON ▪ Cutaneous manifestations that may herald a transformation to acute leukemia ▪ All 3 of the following must be present for diagnosis: 1. Unexplained quantitative change in one or more blood/marrow elements ▪ Hgb < 10 g/dl ▪ ANC < 1.8 x 109/L (Absolute neutrophil count) ▪ Platelets < 100,000/microL 2. Unexplained morphologic evidence of dysplasia on peripheral blood smear/Bone marrow biopsy 3. Blast forms < 20% of the total nucleated cells of bone marrow aspirate or peripheral blood MANAGEMENT ▪ Referral to Heme/Onc ▪ Depends upon the performance score & symptoms ▪ Asymptomatic Patients = serial monitoring of symptoms/blood counts ▪ Updated immunizations ▪ Smoking cessation ▪ Most cases cannot be cured by current treatment options ▪ Goal = maximize quality of life, minimize toxicity of therapy ▪ May live a decade or more without treatment PRE-TREATMENT EVALUATION ▪ CBC w/ diff, peripheral smear, retic count, EPO level, folate, B12, ferritin, iron, TIBC, copper level, HIV testing ▪ HLA typing (in case of future stem cell transplant) ▪ Unilateral bone marrow aspiration & biopsy ▪ ECOG Performance status SYMPTOMATIC TREATMENT ▪ Symptomatic anemia ▪ RBC transfusion ▪ Erythropoetin (EPO) ▪ Symptomatic thrombocytopenia ▪ Platelet transfusion ▪ Neutropenia ▪ Granulocyte colony-stimulating factor (G-CSF) can increase counts but doesn’t change endpoints (survival, infection rates) ▪ Antibiotics for infection DISEASE MODIFYING TREATMENT ▪ Low intensity therapies: ▪ EPO ▪ Azacitidine, decitabine – antineoplastic agent, antimetabolite, DNA methylation inhibitor ▪ Lenalidomide – Antineoplastic agent, immunomodulator ▪ High intensity therapies: ▪ Combination chemotherapy ▪ Allogenic HCT ▪ Recurrent/refractory disease: ▪ Clinical trials LEUKOPENIA LEUKOPENIA = TOTAL WBC’S < 4300/MICROL NEUTROPENIA ▪ Absolute neutrophil count < 2,000/microL ▪ Increased risk of bacterial infection once < 1,000/microL ▪ Causes: ▪ Drugs (chemo, Abx, immunosuppressive agents) ▪ Infections: viral, bacterial, malaria ▪ Nutritional – B12/folate deficiency ▪ Hematologic disease: Leukemia/MDS/aplastic anemia ▪ Hypersplenism – Felty’s syndrome, congestive splenomegaly ▪ Autoimmune disease ▪ Genetics NEUTROPENIA ▪ If febrile + Neutropenia: ▪ Broad spectrum antibiotic ▪ Consider treatment for fungal infection if > 7 days ▪ If chemo induced neutropenia: ▪ Consider G-CSF (granulocyte-colony stimulating factor) to shorten the duration LYMPHOPENIA ▪ Absolute lymphocyte count < 1,000/microL ▪ Causes: ▪ Acute stressful illness ▪ Glucocorticoid therapy ▪ Lymphoma ▪ Immunodeficiency syndrome ▪ Immunosuppressive therapy ▪ Radiation therapy ▪ Chronic illness ▪ Bone marrow failure/replacement MONOCYTOPENIA ▪ Absolute monocyte count < 100/microL ▪ Causes: ▪ Acute stressful illness ▪ Glucocorticoid therapy ▪ Aplastic anemia ▪ Leukemia ▪ Chemo/immunosuppressive therapy EOSINOPENIA ▪ Absolute eosinophil count < 50/microL ▪ Causes: ▪ Acute stressful illness ▪ Glucocorticoid therapy MULTIPLE MYELOMA PATHOPHYSIOLOGY OF MM: ▪ Neoplastic proliferation of plasma cells (from B lymphocytes) producing a monoclonal immunoglobulin (can be seen on SPEP or UPEP) ▪ The plasma cells proliferate in the bone marrow and can result in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures. Normal antibody production  SUSPECT WHEN ONE OR MORE OF THE FOLLOWING ARE PRESENT: ▪ Bone pain with lytic lesions discovered on routine skeletal films or other imaging modalities ▪ An increased total serum protein concentration and/or the presence of a monoclonal protein in the urine or serum (Bence-Jones protein) ▪ Systemic signs or symptoms suggestive of malignancy, such as unexplained anemia ▪ Hypercalcemia, which is either symptomatic or discovered incidentally ▪ Acute renal failure due to concurrent immunoglobulin light chain (AL) amyloidosis MULTIPLE MYELOMA Epidemiology: ▪ 1-2% of all cancers ▪ >17% of hematologic cancers in US ▪ Males slightly > Females ▪ All geographic areas ▪ Median age at diagnosis is 66 y/o CLINICAL MANIFESTATIONS: ▪ Intermittent bone pain that becomes chronic, worse with activity ▪ Anemia ▪ Renal failure and proteinuria ▪ Hypercalcemia ▪ Systemic signs or sx’s suggestive of malignancy (B sx’s) ▪ Often found on radiograph for worsening bone pain ▪ The classic appearance is that of multiple, small, well-circumscribed, punched- out, round lesions within the skull, spine, & pelvis; “lytic lesions” EVALUATION--THOROUGH H&P ▪ Labs ▪ History: ▪ CBC with diff and peripheral smear ▪ Bone pain? ▪ CMP ▪ Constitutional sx’s? ▪ Serum LDH (lactate dehydrogenase) ▪ Neurologic sx’s? ▪ CRP (C-reactive protein) ▪ Infections? ▪ Beta-2 Microglobulin ▪ Serum free monoclonal light chain (SFLC) analysis ▪ Physical: ▪ Serum protein electrophoresis (SPEP) ▪ Should include a detailed neuro ▪ UA exam ▪ 24-hour urine for electrophoresis (UPEP) & immunofixation ▪ Bone marrow bx CRAB: increased plasma Ca++, Renal Insufficiency, Anemia, Bone lesions MULTIPLE MYELOMA ▪ Most frequent findings on peripheral smear: ▪ Rouleaux formation (>50%) ▪ Leukopenia (20%) ▪ Thrombocytopenia (5%) ▪ Imaging ▪ Skeletal survey (suspected MM) ▪ AP & lat skull, AP chest, AP & lat C-spine, T-spine, L-spine, humeri, AP pelvis and femurs ▪ Whole-body CT or MRI reserved for non-dx skeletal survey, compression fx, or possible spinal cord compression MULTIPLE MYELOMA ▪ Treatment: ▪ No curative treatment exists but the available treatment can manage multiple myeloma for years. ▪ Treatment depends on the stage/ aggressiveness of disease ▪ Targeted drug therapy, biological therapy (these drugs use your body’s own immune system to fight myeloma cells), chemotherapy, corticosteroids, radiotherapy and stem cell transplant can be used to prolong life, but relapse is inevitable QUESTIONS? ▪ Sources: ▪ Current Medical Diagnosis & Treatment 2022, Chapter 13 ▪ UpToDate ▪ American Family Physician Journal (aafp.org) ▪ Stat Pearls (https://pmc.ncbi.nlm.nih.gov/)