Hematologic Malignancies 2024 PDF

Qzlet 226 HEMATOLOGIC MALIGNANCIES Laura Blanchard, PA-C Department of Medicine Division of Hematology UNC Cancer Center ACUTE MYELOID LEUKEMIA ○ Clonal proliferation of immature myeloid cells (“Blasts”) with inability to differentiate into mature cells Immature --------------------------------...

Qzlet 226 HEMATOLOGIC MALIGNANCIES Laura Blanchard, PA-C Department of Medicine Division of Hematology UNC Cancer Center ACUTE MYELOID LEUKEMIA ○ Clonal proliferation of immature myeloid cells (“Blasts”) with inability to differentiate into mature cells Immature ------------------------------------ Mature (Blast) (Neutrophil) AML CONT… Fun facts ● ● ● ● ● Most common acute leukemia in adults ~ 1% of adult cancer deaths Median age 65 years old Incidence increases with age Male:Female ratio is 5:3 Clinical manifestations Fever, infections (of any kind) ● Pale, fatigue, shortness of breath ● Bleeding from gums/nose, hematoma, DIC AND/OR ● Vision changes, headache, chest pain, SOB, stroke like symptoms ● Bone pain ● Rash (Leukemia cutis) ● Mental status changes, numbness ● *Symptoms usually present for days/weeks* AML CONT… Exam ● ● Labs ● ● ● Petechiae, raised skin lesion, pale Cranial nerve palsies, altered mental status CBC with differential ○ Pancytopenia (or leukocytosis with anemia/thrombocytopenia) CMP ○ Tumor lysis syndrome (H potassium, H LDH, H phosphorus, H uric acid, L calcium) ○ AKI Peripheral blood smear ○ +/- Blast present Diagnosis * >20% myeloid blasts OR any blast % with t(8;21), inv(16), APL* ● ● ● ● Bone marrow biopsy ○ Hypercellular with >20% blasts ○ Auer rods Flow Cytometry Cytogenetic analysis Myeloid mutation panel AML CONT… ○ Risk stratification ● ● ● ○ Favorable: 60% chance of cure with chemotherapy alone Intermediate: 40% chance of cure Adverse: 10% chance of cure Treatment ● ● Induction, Consolidation, Salvage Therapy types: ○ ○ ○ ○ ○ ○ ○ Cytotoxic Chemotherapy Hypomethylating agents Targeted therapy Apoptosis regulators Antibody drug conjugates Stem cell transplant (allogenic) Clinical Trials AML CONT ---- APL ○ Acute Promyelocytic Leukemia ● Clinical manifestations ○ ○ ● Exam ○ ● Based on WBC and coagulopathies Labs/Diagnostic ○ ○ ○ ○ ● Low or elevated WBC DIC (bleeding and clotting) CBC with differential Peripheral smear ○ “sliding plate” or “dumbbell” appearance BMBx Cytogenetic/FISH ○ t(15;17) – aka “PML-RAR” pathognomonic Treatment ○ ○ ATRA (all-trans retinoic acid) – pushes the cells to differentiate Arsenic – damages PML-RAR (15;17) fusion HIGHLIGHTS – AML ○ ○ Older adults Non-specific HPI/Exam ● ○ ○ Fatigue Pancytopenia OR Elevated WBC with anemia/ thrombocytopenia BMBx >20% blasts ● Auer Rods ● ○ Chemotherapy within days of presentation Low cure rate ○ APL = DIC ○ ALL ○ Clonal proliferation of immature Lymphoid cells (“lymphoblasts”) that can affect B-cell or T-cells ● ○ B cell and T cell ALL differ in their prognosis and treatment but have similar presentations Fun Facts ● ● 2/3 of cases are B-cell types Disease of children ○ ○ ● 75% of cases in children <6 yo ○ 90% survival rate children ○ 60-70% survival in AYA ○ 30-40% survival in adults Second peak of cases >65 yo Cause is unknown ○ Could be associated with radiation or infectious causes CLASSIFICATION ○ Philadelphia (Ph) chromosome positive ALL T(9;22) also know as “BCR-ABL” ● 2-4% of childhood cases; 25% of adult cases ● ○ ○ Incidence increases with age (~50% of pt >60 yo) Ph “like” ALL Gene expression resembling Ph+ disease, but cells lack t(9:22) translocation ● ○ Ph negative ALL ● Various gene mutations ALL CONT… ○ Clinical Manifestations ● ● ● Similar to AML due to bone marrow involvement Fever, infections (of any kind), Pale, fatigue, shortness of breath, weight loss, swollen lymph nodes, bleeding Neuropathic or meningeal symptoms ○ ○ Exam ● ● ● ○ High association with CNS disease; ~50% will relapse in CNS Painless lymphadenopathy Splenomegaly Easy/spontaneous bruising/bleeding Labs/Diagnostic tests ● CBC with differential ○ ● Peripheral blood smear ○ ● ● ● High WBC or Low WBC, pancytopenia Lymphoid blasts Bone marrow biopsy +/- Lymph node biopsy (excision/core needle) Cytogenetics ○ ○ ○ FISH ○ Look for t(9;22) Flow cytometry ○ Look for B cell expression markers (CD19, CD20) Hyperdiploidy/Hypodiploidy ○ Prognostic factor HIGHLIGHTS - ALL ○ ○ ○ Children Ph+ or Ph – (Philadelphia chromosome) Non-specific HPI/exam ● ○ BMBx/blood smear/lymph node biopsy ● ○ ○ ○ Fatigue, current fevers, painless lymphadenopathy, and easy bruising (kids hurt themselves more than adults so more common presentation in kids) Lymphoblasts Chemotherapy within days of presentation (2-3 years of therapy) CNS prophylaxis High cure rate CHRONIC LYMPHOCYTIC LEUKEMIA ○ ○ Progressive accumulation of functionally incompetent monoclonal B lymphocytes. Fun Facts: Most common leukemia in adults (25-30% of all leukemias) ● Median age 70 yeas old ● ○ Incidence increases rapidly with age Male > Female ● Genetic factors are the most likely cause as they present similar throughout the world ● CLL CONT ○ Clinical manifestations ● Typically asymptomatic ○ ● ● Can have waxing and waning painless lymphadenopathy that doesn’t completely clear 5-10% will have typical “B” symptoms ○ ○ Elevated WBC found on routine blood work Weight loss, fever, drenching night sweats, fatigue Exam ● Lymphadenopathy ○ ○ ○ ● ● ● Present in 50-90% of patients Most common sites cervical, supraclavicular and axillary Firm, round, non tender and freely mobile Splenomegaly Hepatomegaly Macules, papules, plaques, nodules, ulcers (leukemia cutis) CLL CONT ○ Work up ● CBC with differential ○ ○ ● Peripheral smear ○ ● Smudge cells (also referred to as basket cells) Flow cytometry ○ ● Elevated WBC count >20K with elevated lymphocyte count ○ ALC >5, many patient present with >100 Anemia and Thrombocytopenia (in advanced stages) Looking for B cell antigen markers on cells Lymph node biopsy ○ Specific changes in the architecture HIGHLIGHTS - CLL ○ ○ ○ Most common leukemia in adults Older adults Non-specific HPI/exam ● ○ High WBC ● ○ ○ High lymphocyte count (usually >100) BMBx ● ○ Fatigue, +/- lymphadenopathy (waxing/waning painless) Smudge cells Can observe some patients Not curable HAIRY CELL LEUKEMIA ○ ○ Chronic B cell lymphoproliferative disorder (lymphoid neoplasm) resulting in accumulation of small mature B lymphoid cells with "hairy" projections within the peripheral blood, bone marrow, and splenic red pulp Fun Facts: ● ● ● ● ● ● Pathophysiology not clearly understood Uncommon (~2% of all leukemias) Slow growing, indolent course Median age 50 years old Male predominance 4:1 Incidence is 3x higher in Caucasians than Blacks HCL CONT ○ Clinical manifestations ● ● ● ● ● ○ Asymptomatic (25%) Fatigue, weakness (25%) Bleeding - gingival, bruising, etc (25%) Abdominal fullness (25%) Usually do NOT have “B” symptoms Exam ● Splenomegaly (80-90%) ○ ○ Extending more than 8 cm below left costal margin in 25% Due to expansion of the red pulp by tumor cells HCL CONT ○ Diagnostic work up ● CBC with differential ○ ● Pancytopenia Peripheral smear ○ “Hairy” cell make up <20% of WBC ○ Irregular cytoplasm and cytoplasmic outlines give the “hairy” appearance BMBx ● Flow Cytometry ● ○ ● Looking for B cell antigen markers on cells Genetic testing ○ BRAF mutation ○ Helpful but not diagnostic HCL CONT ○ Treatment ● Observation ○ Asymptomatic – can observe for months or years with routine blood work (q3 -6 months) When to treat?? ● Cytopenias, Symptomatic splenomegaly, Fatigue or weight loss What to use?? ● Cladribine ○ ○ Daily infusion x 5 days Remission rate in the 90% with 9-11 year disease free survival HIGHTLIGHTS – HAIRY CELL ○ ○ ○ ○ ○ ○ Rare Slow growing disease Asymptomatic with splenomegaly “hairy” projections on cells Can observe some patients Not curable MYELOPROLIFERATIVE DISORDERS ○ ○ ○ ○ Chronic Myelogenous Leukemia - WBC Polycythemia Vera - RBC Essential Thrombocythemia – Platelets Myelofibrosis – scar tissue all of them are specific to a cell line but all of them are slow growing *These are a group of slow growing blood cancers in which the bone marrow makes too many cells within the myeloid linage with relatively normal differentiation. CHRONIC MYELOID LEUKEMIA ○ Uncontrolled proliferation and production of granulocytes (WBC) with fairly normal differentiation ● ○ Philadelphia Chromosome t(9;22) is pathognomonic Fun Facts ● ● ● ● AML = stuck in blast phase, CML = multiple ton of mature 15-20% of all adult leukemias Median age 50-60 years old Slight male predominance Only known risk factor is ionizing radiation Normal smear CML smear CML CONT ○ Clinical course – 3 phases ● Chronic phase (85% of patients) ○ ● Accelerated phase ○ ○ ○ ● <10% blasts; usually asymptomatic 10-20% blasts Plt <100K (not related to therapy) Cytogenetic changes Blast phase ○ ○ >20% blasts Extra medullary disease CML CONT Clinical manifestations *Symptoms vary depending on phase of disease at presentation ○ Asymptomatic ● Fatigue, Weight loss, Sweats ● Abdominal fullness ● Bleeding ● ○ Exam Normal ● Splenomegaly ● Pale ● CML CONT ○ Diagnostic work up ● CBC with differential ○ ○ ○ ● Bone marrow biopsy ○ ● WBC >100K Increased basophils and eosinophils Normal OR Elevated platelet count (>600K) To calculate blast count Cytogenetic/FISH ○ Philadelphia chromosome present (~95% of patients) CML CONT ○ Treatment Chronic phase: ○ TKIs : Imatinib and dasatinib ○ Multiple generation of drug available ○ Drug choice - patient specific based on side effect profile Accelerated phase ○ ○ TKIs ○ If previously treated with TKIs, send TKI mutation testing (resistance) – requiring different generation TKI for tx Stem cell transplant Blast phase ○ ○ AML induction chemotherapy + TKIs Stem cell transplant *Hydrea: Used to decrease WBC count while awaiting diagnosis HIGHLIGHTS - CML ○ ○ ○ ○ High WBC Philadelphia chromosome 3 phases of disease Non-specific HPI/Exam ● ○ Fatigue, splenomegaly Treatment = Imatinib (Gleevec) POLYCYTHEMIA VERA (PV) ○ Clonal proliferation of myeloid cells resulting in elevated red blood cells. ● ○ Characterized by a JAK2 mutation Fun Facts: Median age 60 years old ● Slight male predominance ● Risk factors unknown ● PV CONT ○ Clinical Manifestation ● ● ● ● ● ○ Asymptomatic (found incidentally) Headache, dizziness, vision changes Itching (usually post-bath) GI complaints (early satiety, ulcers) Complications of clotting (CVA, MI, DVT, PE, superficial thrombophlebitis) Exam Normal ● Hypertension ● Splenomegaly ● Excoriation of the skin ● Major Criteria PV CONT ○ Diagnostic work up ● CBC with differential ○ ● ● ● Elevated Hgb >16 EPO level (low) JAK2 mutation analysis +/- Bone marrow biopsy ○ Used when diagnosis is questionable 1. Hgb/Hct > 16.5/49 in male; 16/48 in female OR Increased red cell mass 2. BMBx: hypercelluar; trilineage growth; varying size of mature megakarycytes 3. Presence of JAK2 mutation Minor Criteria 1. Subnormal serum EPO levels Diagnosis of PV requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion *Diagnosis made by sustained elevation in hgb/hct, a low EPO level AND a JAK2 mutation* ○ Treatment ● Phlebotomy ○ ● Low dose Aspirin (unless contraindicated) ○ ● To prevent thrombosis Hydrea ○ ● Maintain hematocrit <45% (titrate to needs; starting once weekly) Decreases bone marrows ability to make RBCs Ruxolitinib (JAK2 inhibitor) HIGHLIGHTS – PV ○ ○ ○ ○ Older adults Elevated Hemaglobin Itching after shower Phlebotomy + ASA ESSENTIAL THROMBOCYTHEMIA (ET) ○ ○ Clonal proliferation of myeloid cells resulting in elevated platelets. Fun Facts 90% of cases have JAK2, CALR or MPL mutation ● 1/3 of all myeloproliferative disorders ● Life expectancy is near normal population ● Female predominance ● ● Median age 60 years old; increases with age Normal smear Essential thrombocythemia ET CONT ○ Clinical manifestations ~50% are found incidentally ● Headache, dizziness, vision changes ● Thrombosis events and bleeding ● First trimester fetal loss ● ○ Exam Normal ● Splenomegaly (moderate size) ● ET CONT ○ Diagnostic work up ● CBC with differential ○ ○ ● CMP ○ ● Elevated platelets >450K (median count 1 million) ○ Platelet size varies RBC and WBC usually normal To rule out other causes BMBx ○ ○ Genetic testing ○ JAK2 mutation 65% Megakaryocytes Diagnostic Criteria Major Criteria 1. Platelet count ≥450 × 109/L 2. BMBx with increased megakaryocytes 3. Not meeting criteria CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms 4. Presence of JAK2, CALR, or MPL mutation Minor Criteria 1. Presence of a clonal marker or absence of evidence for reactive thrombocytosis ET CONT Treatment Low risk: ○ Observation ● Low-dose Aspirin (optimal dosing unknown) ● ○ Avoid in patient with acquired von Willebrand disease (thrombocytosis may alleviate aVWD and reduce bleeding) High and intermediate risk: ● Hydrea ○ Cytoreduction to target plt 100K – 400K Others: ● Platelet pheresis (take away plt from circulation) ○ ● Used in extreme thrombocytosis prior to cytoreduction as the intervention is temporary Ruxolitinib (JAK2 inhibitor) HIGHLIGHTS – ET ○ ○ ○ ○ Older adults Elevated platelets Blood clots/bleeding issues Observation  ASA  Hydrea MYELOFIBROSIS ○ ○ Clonal proliferative disorder with abnormal megakaryocytes (platelets) and bone marrow fibrosis (scarring) resulting in impaired hematopoiesis Fun Facts: Rare ● Median age 65 years old ● Familial occurrence have been reported ● MF CONT ○ Clinical manifestations Asymptomatic (~30%) ● Fatigue (~70%), weight loss, bone pain, night sweats ● ○ Exam Normal ● Splenomegaly ● Hepatomegaly ● MF CONT ○ Diagnostic work up ● CBC with differential ○ ○ ● Peripheral smear ○ ○ ○ ● Anisocytosis (varying RBC size) Poikilocytosis (varying RBC shape) Teardrop- shaped RBCs BMBx ○ ● Anemia (usually hgb <10) WBC and platelets can be mildly increased or decreased Reveals fibrosis (scarring) Genetic testing ○ JAK2, MPL and CALR MF CONT ○ Treatment ● Blood transfusion PRN ○ ● Clinical trials ○ ● JAK2 inhibitor Hydrea ○ ● Need better treatment options Ruxolitinib ○ ● Given progressive anemia Controls proliferation Stem cell transplant (allogenic) ○ Only chance of cure HIGHLIGHTS - MF ○ ○ ○ ○ ○ ○ Rare Older adults Cell lines don’t function well due to bone marrow scarring Teardrop cells BMBX= scarring Treatment = stem cell transplant MYELODYSPLASTIC SYNDROME ○ Group of diverse blood disorders characterized by abnormal development (dysplastic) and ineffective production in one or more blood/marrow elements (RBCs, WBCs or platelets). ● Can develop after: ○ ○ ○ ○ ○ Chemotherapy (alkylating agents) ○ Associated with 5q- and 7q- (deletions) Environmental (benzene) Radiation (therapeutic or accidental) De novo Fun Facts: ● ● ~10,000 cases diagnosed annually in the US Median age >65 years old ○ ○ ● ● Younger if treatment related Incidence increases with age Male predominance Sometimes referred to as “pre-leukemia” MDS CONT ○ Clinical manifestations Asymptomatic ● Fatigue, dizziness ● Infection ● Easy bruising or bleeding ● ○ Exam Normal ● Pale ● Petechiae ● MDS CONT ○ Diagnostic work up ● CBC with differential ○ ○ ○ ● Peripheral smear ○ ● Pancytopenia (anemia, neutropenia, thrombocytopenia) Can have isolated anemia ○ Low reticulocyte response <20% blasts >10% Dysplasia BMBx MDS CONT MDS CONT ○ Treatment ● Supportive Care ○ ○ ● Low intensity ○ ● Antibiotics for infections Blood/platelet transfusions Hypomethylating agents (Decitabine) High intensity ○ ○ Combination chemotherapy Stem cell transplant (allogenic) HIGHLIGHTS – MDS ○ ○ ○ Older adults Abnormal (dysplastic) development of cells in one or more blood cell lines Difficult to treat HODGKIN LYMPHOMA ○ Lymphoid neoplasm caused by the proliferation of malignant Hodgkin/Reed-Sternberg cells mixed with non-malignant inflammatory cells and a variable degree of fibrosis ● Classification: ○ ○ ○ Classical Hodgkin Lymphoma (90%) ○ Nodular sclerosis cHL most common subtype Nodular Lymphocyte-predominant HL (10%) Fun Facts: ● ● ● 10% of all Lymphomas 8500 new cases annually Bimodal age distribution ○ ● Esptein-Barr Virus (EBV) linked to pathogenesis ○ ● ~20 years old and ~70 years old Although risk of HL following EBV is very small Geography, HIV infections, immunosuppression and family history also play a role HL CONT ○ Clinical manifestations Non-tender lymphadenopathy ● “B” symptoms/Constitutional symptoms ● ○ Fever, night sweats, weight loss, fatigue Generalized itching ● Cough, Chest discomfort and SOB ● ○ ○ Due to mediastinal mass Exam ● Non-tender, firm, rubbery lymphadenopathy ○ ● Cervical and supraclavicular nodes most common Splenomegaly Lymph node regions in lymphoma HL CONT ○ Diagnostic work up ● CBC with differential ○ ● ESR (erythrocyte sedimentation rate) ○ ● Identify sites of disease for biopsy and staging Lymph node biopsy ○ ● High risk marker in localized disease CT scan /PET scan ○ ● Often normal Excisional or core BMBx ○ Morphology ○ Reed-Sternberg cells ● ○ “Owl’s eyes” appearance Flow cytometry ○ B cell markers and EBV antigens HL CONT ○ Lymphoma Staging Stage Involvment I Single lymph node region or lymphoid structure II Two or more lymph node regions/structure on the SAME side of the diaphragm III Lymph node regions/structures on BOTH sides of the diaphragm IV Diffuse involvement of one or more extranodal organ/tissue HL CONT ○ Treatment ● ABVD + Radiation ○ ○ ○ Doxorubicin (anthracycline), Bleomycin, Vinblastine, Dacarbazine Site involvement radiation Monitoring PET scan within 3 months of therapy to document negative disease ● CT scan at 6, 12 and 24 months ● F/u visits every 3-6 months for 1-2 years, then every 6-12 months until 3 years, then annually ● HIGHLIGHTS – HODGKIN ○ ○ ○ ○ ○ ○ Bimodal age (20s and 70s) Linked to EBV Non tender, firm, mobile lymphadenopathy in the neck “B” symptoms Reed Sternberg cells (owls eyes) Chemotherapy + radiation NON-HODGKIN LYMPHOMA NON- HODGKIN’S DISEASE ○ Group of malignant neoplasms that derive from progenitor and mature B cells and T cells and rarely natural killers cells. B-Cell Lymphoma T-cell Lymphoma NK cell Lymphoma Follicular Peripheral T-Cell Extranodal NK-Cell Marginal Zone Breast Implant-Associated Anaplastic Large Cell Mantle Cell T-Cell Large Granular Lymphocytic Diffuse Large B-Cell Adult T-Cell Burkitt T-Cell prolymphocytic AIDS-Related B-Cell Hepatosplenic Gamma-Delta T-Cell Lymphoblastic Post-Transplant Lymphoproliferative disorders Castleman’s Small Lymphocytic Lymphoma/CLL NHL CONT Divided into Aggressive and Indolent lymphomas ○ Highly Aggressive ● ○ Burkitt Lymphoma Aggressive Diffuse Large B cell Lymphoma (DLBCL) ● AIDS-Related B cell Lymphoma ● Post-Transplant Lymphoproliferative disorder (PTLD) ● Peripheral T cell Lymphoma ● ○ Indolent Follicular lymphoma ● Marginal Zone Lymphoma ● Mantle Cell Lymphoma ● BURKITT LYMPHOMA Highly aggressive germinal center B-cell lymphoma characterized by the translocation 8;14 of the MYC gene. ○ Fun Facts: Clinically divided into 3 forms: ○ - Endemic (African) - - Sporadic (non-endemic) - - Incidence is ~50-fold higher than US Accounts for 30-50% of all childhood cancers in Africa EBV positive US and Western Europe Accounts for 30% of childhood lymphomas and <1% of adult NHL Peak age is 11 years, with adult median age of 30 More common in Caucasians Male predominance 4:1 Immunodeficiency-associated - HIV patients with high CD4 counts (all other forms of HIV-associated lymphoma have low CD4 counts) Incidence has NOT decreased with advance in HIV treatment BL CONT ○ Clinical manifestations +/- “B” symptoms ● Rapidly growing mass ● ○ ● ○ Develop in days Electrolyte disturbances (from Tumor lysis syndrome) Exam ● Mass ○ ○ ○ African: Jaw or facial bone tumor Sporadic: Abdominal, Jaw/facial bones, bone marrow, CNS Immunosuppressed: lymph node, bone marrow, CNS BL ○ Diagnostic Work up ● CBC w differential ○ ● CMP, uric acid, LDH ○ ○ ● ● ○ ○ ○ Disease involvement Testicles are “sanctuary sites” for disease with high association for CNS involvement Ki-67 nearing 100% (very aggressive) Flow Cytometry ○ ● “Moth-eaten” appearance (low power) “starry-sky” pattern Proliferation index ○ ● Staging (Lymphoma staging I-IV) Disease involvement BMBX/Lumbar Puncture ○ ● “Starry-sky” pattern Tissue Biopsy ○ ● TLS Organ dysfunction HIV testing PET/CT scan ○ ● cytopenias B- Cell antigens Cytogenetics/FISH ○ Myc translocation; t(8;14) most common BL CONT ○ Lymphoma Staging Stage Involvment I Single lymph node region or lymphoid structure II Two or more lymph node regions/structure on the SAME side of the diaphragm III Lymph node regions/structures on BOTH sides of the diaphragm IV Diffuse involvement of one or more extranodal organ/tissue BL CONT ○ Treatment ● TLS prophylaxis ○ ● Pre-phase steroids ○ ○ ● ● AFTER tissue biopsy Reduce tumor burden which decreases risk of TLS Clinical trials Intensive chemotherapy ○ ○ ● Sevelamer, allopurinol, IV fluids R-CODOX-M (4 cycles) ○ Rituxan, Cyclophophamide, Vincristine, Doxorubicin, HDMethotrexate Dose adjusted R-EPOCH (6 cycles) ○ Rituxan, Etoposide, Prednisone, Vincristine, Doxorubicin, Cyclophosphamide ○ Used in older adults, less fit patients or HIV – related Intrathecal chemotherapy ○ CNS prophylaxis (1-2 IT treatments per cycle) HIGHLIGHTS – BURKITT ○ ○ ○ ○ ○ Young adolescents Fast growing abdominal mass (US) or Jaw mass TLS Starry sky appearance on biopsy Chemotherapy with CNS prophylaxis DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) ○ ○ A diverse group of tumors consisting of large B cells with diffuse pattern and high proliferation rates. Fun Facts: ● Most common subtype of Non-Hodgkin lymphoma ○ 25% of all cases Highest incidence in Blacks ● Median age 65 yo ● Male predominance ● Can arise from other indolent lymphomas or de novo ● DLBCL CONT ○ Clinical manifestation Rapidly growing lymphadenopathy ● +/- “B” symptoms ● Symptoms of obstructive mass ● ○ ○ Abdominal pain, SOB, swelling, SVC syndrome Exam ● Mass ○ ● Neck, abdomen or mediastinal most common but can be anywhere Evidence of obstructive Mass ○ bowel obstruction, JVD, edema, SVC syndrome DLBCL CONT ○ Diagnostic work up ● CBC w differential ○ ● CMP, uric acid, LDH ○ ○ ● ○ ○ ○ Ki-67: 40-90% (aggressive) Flow Cytometry ○ ● Staging CNS disease Proliferation index ○ ● Excisional or less preferred core biopsy Morphology reveals Large cells in diffuse pattern BMBx/Lumbar puncture ○ ● Staging (Lymphoma staging I-IV) Disease involvement Tissue Biopsy ○ ● TLS Organ dysfunction PET/CT scan ○ ● Cytopenias can occur B- Cell antigens Cytogenetics/FISH DLBCL DLBCL CONT ○ Lymphoma Staging Stage Involvment I Single lymph node region or lymphoid structure II Two or more lymph node regions/structure on the SAME side of the diaphragm III Lymph node regions/structures on BOTH sides of the diaphragm IV Diffuse involvement of one or more extranodal organ/tissue DLBCL CON ○ Treatment ● Limited stage disease (Stage I or II) ○ ○ ● R-CHOP (Rituxan, Cyclophosphamide, Doxorubicin, Vincristine and prednisone) Radiation to affected area Advance stage disease (Stage III or IV) – based on molecular subtype ○ ○ R-CHOP DA-R-EPOCH HIGHLIGHTS – DLBCL ○ ○ ○ ○ Most common NHL Older adults Lymphadenopathy Tissue biopsy ● ○ Large cells in a diffuse pattern Chemotherapy FOLLICULAR LYMPHOMA FOLLICULAR LYMPHOMA ○ ○ Indolent lymphoma of the follicle center with germinal center expressed B cell markers Fun Facts: ● ● ● ● ● Most common indolent lymphoma 35% of all NHLs Caucasian predominance Incidence increases with age; median age 65 years old 85% have the t(14:18) FL CONT ○ Clinical manifestation Painless adenopathy that waxes and wanes ● “B” symptom (20%) ● Asymptomatic ● ○ Exam ● Lymphadenopathy ○ Cervical, axillary, inguinal and/or femoral regions FL CONT ○ Diagnostic work up ● CBC with differential ○ ● Tissue biopsy ○ ● Staging Characteristic nodules close together and varying in size and shape Flow cytometry ○ ○ ● Lymph node of FL Morphology ○ ● Excision or core BMBx ○ ● Usually normal Germinal center B cell phenotype Cytoplasm positive for BCL2 (80-90%) Cytogenetic/FISH ○ t(14;18) FL CONT ○ Treatment Observation (stage I or II) ● Chemotherapy (stage III or IV) -75% of patients ● ○ ○ ○ ● R-CHOP Rituxan + Bendamustine Stem cell transplant +/- Maintenace therapy ○ Rituxan q2 months x 2 years (controversial) – no prolonged overall survival HIGHLIGHTS – FOLLICULAR ○ ○ ○ ○ Most common indolent lymphoma Older adults Slow growing Asymptomatic for years ● ○ Tissue biopsy ● ○ +/- waxing and waning lymphadenopathy Multiple nodules of varying size Observation or chemotherapy based on stage MULTIPLE MYELOMA MULTIPLE MYELOMA ○ Proliferation of plasma cells producing a monoclonal immunoglobulin ● ○ One immunoglobulin (IgM, IgA, IgG) is over produced MM is a continuum ● MGUS (Monoclonal gammopathy of unknown significance) ○ ○ ○ ○ ● Smoldering MM ○ ○ ○ ○ ● >10% plasma cells in bone marrow Asymptomatic; no end-organ damage >3 g/dL of serum monoclonal protein Observation MM ○ ○ ○ ○ ● <10% plasma cells in bone marrow Asymptomatic; no end-organ damage <3 g/dL of serum monoclonal protein Observation >10% plasma cells in bone marrow Symptomatic; end-organ damage (CRAB) Any spike of serum monoclonal protein Treatment Plasma Cell Leukemia ○ ○ Any amount of circulating serum plasma cells Treatment MM CONT ○ Proliferation of plasma cells producing a monoclonal immunoglobulin ● ○ One immunoglobulin is over produced (IgA or IgG most common) Fun Facts: ● ● ● ● ● Accounts for 1-2% of all cancers and 17% of hem malignancies Incidence is 2-3 times higher Blacks than Whites Male predominance Median age 66 years old Small set of familial cases (not well understood) An Antibody – which are effected in MM MM CONT ○ Clinical manifestation ● ● Fatigue Bone fracture with minimal trauma (slamming the door) ○ ● Bone pain ○ ● ○ Usually from thoracic or lumbosacral areas Possible cord compression Hyperviscosity (thick blood) – rare ○ ○ Usually back or chest Numbness/tingling ○ ● “pathologic fractures” Bleeding, headache, vision change, etc Exam ● ● ● Pain over bone Pale Paresthesias, weakness, loss of bowel/bladder control MM CONT ○ Diagnostic work up ● CBC with differential ○ ○ ● CMP ○ ○ ● ○ Determines type (ex: IgG Kappa) BMBx ○ ● M-spike Urine dipstick is usually negative for protein Immunofixation ○ ● Monoclonal spike “M-spike” UPEP (urine protein electrophoresis) ○ ● Rouleaux formation – “stacking poker chips” SPEP (serum protein electrophoresis) ○ ● Elevated Creatinine Hypercalcemia Peripheral smear ○ ● Cytopenia Plasma cells in peripheral blood = plasma cell leukemia >10% plasma cells Imaging ○ ○ Skeletal survey (X-ray) ○ “Punched out” lesions CT, MRI or PET (more sensitive) Rouleaux formation MM CONT Diagnosis….. CRAB criteria Clonal plasma cell population + One disease related end organ impairment (CRAB) ○ C – hyperCalcemia R – Renal insufficiency A - Anemia B - Bone lesions MM CONT ○ Staging ● ISS (Internataion Staging system) ○ ○ ○ ● Stage I – Beta-2 Microglobulin <3.5 mg/L and serum albumin ≥3.5 g/dL Stage II - neither stage I nor stage III Stage III – Beta-2 Microglobulin ≥5.5 mg/L Median overall survival ○ ○ ○ Stage I - ~5 years Stage II - ~3.5 years Stage III - ~2.5 years MM CONT ○ Treatment Bortezomib, Lenalidomide, Dexamethasone ● Stem Cell Transplant (autologous) ● Lenalidomide maintenance therapy ● ○ Supportive Care Radiation ● Surgery (fractures) ● Bisphosphonates (bone strength) ● *Several other therapy regimens for relapsed disease or Non-transplant candidates HIGHLIGHTS - MM ○ ○ ○ ○ ○ Older adults with pathologic fracture Plasma cell problem >10% plasma cells in bone marrow CRAB criteria SPEP/UPEP ● ○ ○ ○ ○ M-spike (monoclonal spike) Rouleaux formation Punched out lesion Chemotherapy Not curative WALDENSTROM MACROGLOBULINEMIA (WM) – AKA LYMPHOPLASMACYTIC LYMPHOMA ○ ○ Chronic, slow growing lymphoproliferative disorder which affects B cells causing them to overproduce abnormal IgM proteins Fun Facts: Rare – 3 per million people per year ● Median age 70 years ● Large Caucasian predominance ● Familial cases in up to 20% ● WM CONT ○ Clinical manifestations Asymptomatic ~25% ● Weakness, fatigue, weight loss, oozing blood from gums ● Anemia, lymphadenopathy, hepatosplenomegaly ● ○ ● Hyperviscosity, peripheral neuropathy – common ○ ○ Bone marrow/organ infiltration IgM monoclonal protein Exam Normal ● Lymphadenopathy ● Hepatosplenomegaly ● WM CONT ○ Diagnostic work up ● CBC with differential ○ ● Peripheral smear ○ ● Rouleaux SPEP/Immunofixation ○ ● Anemia M spike (from IgM) BMBx ○ >10% plasma cell differentiation Serum IgM Symptoms Bone marrow involvement Waldenstrom Macroglobulinemia High levels Present – lacks bone involvement >10% MGUS Low levels Absent <10% Multiple Myeloma Rare (<0.5%) Present - CRAB >10% WM CONT ○ Treatment ● Chemotherapy + Immunoglobulin ○ ○ ● Bendamustine + Rituximab Bortezomib + Dexamethasone + Rituximab Stem cell transplant (Autologous) HIGHLIGHTS - WM ○ ○ ○ Rare Older adults SPEP/immunofixation ● ○ M-spike - IgM NO bone involvement or CRAB symptoms AMYLOIDOSIS ○ Extracellular tissue protein deposits (fibrils) which clump together to become insoluble ● Several types, most common: ○ ○ ○ AL amyloidosis – plasma cell dyscrasia by light chain fragments AA amyloidosis – recurring inflammation results in production of amyloid A protein which forms amyloid deposits Fun Facts: Can be hereditary (rare types) ● ~2,000 cases per year ● Median age ~65 years old ● Male predominance ● AMYLODI CONT ○ Clinical manifestation ● Skin changes, Edema, Speech changes, etc *All symptoms are related to location and amount of protein deposits ○ Exam ● ● ● Waxy thickening of skin Pleural effusion Enlarged muscles (tongue, deltoids) ○ ● ● ● “Shoulder pad sign” Heart failure (edema, arrhythmias) Neuropathy Bleeding (abnormal liver function) AMYLOIDOSIS CONT ○ Diagnostic work up ● Work up to rule out other causes… ○ CXR, EKG, Thoracentesis, etc Tissue biopsy ● Urine analysis ● ○ Increased protein BMBx ● Pathology ● ○ Congo red stain ○ Results in apple-green birefringence with polarized light microscopy AMYLOID CONT ○ Treatment ● Stem cell transplant (autologous) ○ ● Generally without induction treatment Bortezomib + Cyclophosphamide + Dexamethasone (CyBorD) ○ Transplant delayed or no eligible HIGHLIGHTS – AMYLOID ○ ○ ○ ○ ○ ○ RARE Older adults Protein depositions (enlarged tongue or heart) Tissue biopsy Not curative High mortality rate