Hematology

     

    Summary of Heme Oncology

    Heme Malignancies.png

    Cell Lines (Simple)

     

    Hematopoiesis.png

     

    Hematopoietic Growth Factors

    • Erythropoietic Stimulating Agents (ESAs)
      • Benefits:
        • Increase Hb
        • Can improve anemia-related symptoms
      • Risks!!! (use with caution)
        • Increase in all-cause mortality, cardiovascular disease, and stroke (thrombogenic)
        • Lower survival in patients with solid tumors (perhaps due to increased thromboembolism or inferior level of tumor control??)
        •  
      • Indications:

        • Generally use of erythropoietic growth factors in cancer is restricted to those with symptomatic chemo-related anemia with Hb < 100 and treatment is NOT curative. (Do not target >110).
        • Must check/follow iron stores, target:
          • Iron Saturation > 20%, and ferritin >100 
          • Works better when iron levels are sufficient
      • In dialysis: Target Hb=100-110 (lower than before)... Use lowest dose necessary to reduce the need for erythrocyte transfusion.
      • Check Iron stores before and during treatment.  
         
    • GCSF (GmCSF no longer avaialble)
      • Avaialble in regular and pegylated form.
      • Stimulate production of neutrophils in:
        • Primary prophylaxis in myelosuppressive chemo and cancers with high risk of febrile neutropenia such as lung/bladder ca...
        • Also used in infectious complications in non-maligant diseases (i.e. autoimmune neutropenia) with high risk of infection.
      • DO NOT deliver these agents <24hrs after chemo (promote cell cycle).
    • Thrombopoietin Memetics
      • Restricted to use only in ITP

    Hematopoietic Stem Cell Transplant (HSCT)

    • HSCT used to treat:
      • Hematologic Malignancies
      • Congenital/Acquired bone marow failure syndromes
      • Other disorders...
    • Two sources: Autologous (own) and Allogeneic (from HLA-matched donor).
    • Steps:
      • 1. Mobilize stem cells with high doses of GCSF, increases CD34+ stem cells (stem cell marker).
      • 2. Conditioning therapy
        • Give myeloablative doses of cytotoxic chemotherapy +/- total body irradiation.
        • Eradicate residual disease + allow stem cells to engraft.
        • High risk (splenic, pulmonary hemorrhage), so now looking at less-intensive myeloablative therapy. (i.e. fludarabine).
          • Also allows some older patients to be eligible. (>60yo)
          • Using lower-intensity conditioning decreased early toxicity/mortality.
    • The idea with autologous SCT is a rescue to repopulate the BM, but the idea with allogeneic is graft-vs-tumor effect (it is a treatment).  Unfortunately also get graft-vs-host (GVHD) as well.j
    • GVHD (generally from allogeneic)
      • Transplanted lymphocytes attack organs --> skin (rashes), GI tract (diarrhea), Liver (veno-occlusive disease, transamanitis), Eyes, Lungs, Bone Marrow.
      • Can moderate response with MTX and calcineurin inhibitors.

     

    Thrombocytopenia and Anticoagulation

    • Platelets 20,000-50,000 = DVT prophylaxis only (other anticoagulation including antiplatelet agents generally contraindicated)
    • Platelets < 20,000 = No anticoagulation. (even if ACS)

     

    Lymphadenopathy

    • Causes:
      • Cause Examples
        Cancer Hematological vs. Non-Hematological
        Hypersensitivity Serum sickness, Drugs, Vaccination, GVHD
        Infection

        Viral (EBV, CMV, HIV)

        Bacterial (TB, Syphilis, cat scratch etc...)

        Chlamydial (LGV)

        Protozoan (Toxoplasma)

        Fungal (Histo)

        Rickettsia (Scrub Typhus)

        Helmith (filariasis)

        Connection Tissue Lupus, RA, etc.
        Atypical LPD Castleman, AILD
        Granulomatous Disease Sarcoid, Wegener, berylliosis, silicosis
        Other Sinus histiocytosis and massive lymphadenopathy (Rosai Dorfman)
    • Malignancy?
      • Factor Interpretation
        Age of Patient More likely in older
        Location (tonsillar less likely malignant, inguinal more likely)
        Size Cancer more likely with incr. size

        Consistency

        Tenderness

        Appearance

        Mobility

        Rocky hard (non-hematological cancer)

        Rubbery (Lymphoma)

        Tender (Infection)

        Fixed (non-heme cancer)

        Local v General Local more likely reactive
        Other fever, splenomegaly, etc..
    • History:
      • Cat/kittens scratch? (toxoplasomosis)
      • Undercooked meat? (Toxoplasmosis)
      • Tick Bites (Lyme/Tularemia)
      • TB (TB adenitis)
      • Transplant (CMV, HIV, PTLD)
      • High Risk Sex (HIV, Syphilis, HSV, CMV, HepB)
      • IVDU (HIV endocarditis, HepB)
      • Hunter/sTra
      • Sothern US (coccidiomycosis)
      • Medications?
        • Allopurinol, Atenolol, Captopril, etc.... through hypersensitivity.

     

    Splenomegaly

    • Causes
      • Cause Example  
        Passive Congestion Portal HTN, Budd-Chiari, CHF  
        Work Hypertrophy

        Chronic extravascular Hemolysis

        (herediatory spherocytosis)

         
        Infiltrate Non-Neoplastic

        - Infections, connective tissue dz (SLE, RA)

        granulomas (sarcoid)

        - All Myeloid/lymphoid malignancy (CML, MPN, Lymphoma)

        - Any (usually not that apparent)

         
        Neoplastic Hematological
        Non-Hematological
        Acellular Infiltrate Amyoid, storage disorders (Gaucher, etc)  

     

    Hematologic Emergencies

    • Leukostasis
      • Lower WBC (Hydroxyurea, aggressive hydration)
    • DIC
      • Give cryoprecipitate Fibrinogen > 1-1.5
    • Tumor Lysis
      • Allopurinol (Xanthine oxidase inhibitor)
      • Rasburicase (converts uric acid) - add if a lot of electrolyte abnormalities

     

    General Approaches

    High Eosinophils

    • CHINA mnemonic
      • Connective tissue diseases
      • Helminthic infection
      • Idiopathic [HES]
      • Neoplasia
      • Allergy
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