3.26 GOORHA BM Failure/Hematopoietic Stem Cell Transplants Flashcards Preview

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Flashcards in 3.26 GOORHA BM Failure/Hematopoietic Stem Cell Transplants Deck (16):
1

BM Failure

Pancytopenia due to failure of BM to produce blood cells

-Symptoms of Anemia: diff breathing, chest pain and fatigue

-leukopenia/neutripenia: fever, infection and mouth sores

-Bleeding from thrombocytopenia

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Aplastic Anemia

-Typically younger patients

-Peripheral pancytopenia and hypocellular BM

-Path: reduction or depletion of hematopoietic precursor stem cells with decreased production of cell lines

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Aplastic Anemia: Congenital

Fanconi's anemia: symptomatic ~5yrs and progressive BM hypoplasia, hyperpigmentation of the skin and small stature Familial aplastic anemia: subset of Fanconi's, congenital defects are absent but still ahve hematologic symptoms

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Aplastic Anemia: Aquired

-Most are Idiopathic

-Exposure to Ionizing radiation

-Chemical agents (benzene ring, chemo agents)

-Idiosyncratic rxn to some commonly used drugs

-Infections: mononucleosis, infec hepatitis, parvovirus and cytomeglavirus infec, and miliary tuberculosis

-Pregnancy (rare)

-Paroxysmal nocturnal hemoglobinuria

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Aplastic Anemia Lab Findings

-Severe pancytopenia (w/ relative lymphocytosis-lymphocytes live a longer time)

-Normochromic, normocytic RBCs (s/t macrocytic)

-Mild to mod anisocytosis and poikilocytosis

-Decreased reticulocyte count*** Hypocellular bone marrow with yellow marrow (fat) replacing

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Treatment of Aplastic Anemia

-Supportive care (transfusions, abs)

-Immunosuppressive regimens: shown to improve count (points to auto immuno for idiopathic cause) Hematopoietic cell transplantation (HSCT)

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Pure Red Cell Aplasia

-Selective Decrease in erythroid precursors cells in BM

-WBCs and Plts are unaffected Acquired:

(1) transitory with viral or bacterial infections,

(2) hemolytic anemias may suddenly halt erythropoiesis

(3)pts with thymoma: T-cell mediated response against erythroblasts or erythropoietin

Treatment: Supportive care and immunosuppression

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Myelodysplastic Syndromes

-terminate in AML

-BM is usally normocellular or hypercellular w/ qualitative abnorms (1 or more cell line)

-PB shows dysplastic cells including (1) nucleated RBCs, (2) oval macrocytes, (3) pseudo-Pelger-Huet PMNs (hyposegmented neutros) with hyperchromatic clumping, (4) hypogranulated neutros and  (5) giant biazzare platelets

-Ringed sideroblasts in BM

A image thumb
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MDS vs Aplastic Anemia

Clonal expansion of the abnormal cells results in the production of cells which have lost the ability to differentiate.

***presence of a neoplastic clone differentiates MDS from aplastic anemia

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MDS Treatment

-Goal: control of symptoms, decrease progression to AML

-Supportive care: blood product support and hematopoietic growth factors

-Chemo: 5-azacytidine and decitabine (hypomethylating agents), shown to decrease transfusion requirements and retard progression to AML

-Lenalidomide: only use for 5q-syndrome

-HSCT esp in younger patients (<60), more severly affected pts, offers potential curative therapy

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HSCT

-Transplantation of hematopoietic progenitor cells that have the ability to proliferate and repopulate the marrow spaces, can harvest from PB (less painful)

-HSC: have ability to find way to bone marrow with IV infusion and can cryopreserve (freeze)

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Autologous HSCT

-Use of stem cells collected from a patient, stored and freezer to be reinfused or transplanted at a later date following high dose chemo

-Allows to use high doses of chemo that would otherwise be too toxic for BM

-Rescue hematopoetic system after chemo

-use mainly in treatment of LYMPHOMAS and MULTIPLE MYELOMA

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HSCT Allogenic

-uses related or unrelated HLA matched donors as the source of stem cells

-Advantages: can be used when patients BM fails (aplastic anemia and MDS)

-When pts has certain disease (leukemia or lymphoma) the donor cells can attack theme tumor cells via graft vs disese to prevent tumor relapse (use a new immune system)

Disadvantages: higher risk of chemo complications, high risk of infection (CMV, EBV, fungal and parasitic), risk of rejection and complications of graft vs host disease

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Types of Allogenic HSCT

Myeloablative: chemo right before or right after transplant, ablate BM. Immunosuppressive effect (prevents rejection) high rate of complications esp in older patients

Non-Myeloablative: lower doses of chemo, too low to eradicate all of the BM of host. Just enough chemo to prevent rejection. Lower risk of transplant related mortality

-For older patients, used when graft vs host is wanted in order to attack the cancer (CML AML, Lyphoma)

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Complications of Allogenic HSCT

-Infection: have to have immunosuppression, usually have to be re-vaccinated with childhood vaccines

-Veno-Occlusive disease: severe liver injury, increased bilirubin, hepatomegaly and fluid retention are clinical signs of this condition.

-Mucositis: injury of mucosal lining (chemo) treat with pain medication

-GvHD: inflamm disease attack of new marrow on host

--Acute GvHD: occurs within 3 months prevent with cyclosporine and MTX (immune suppress) and treat with high dose steroids

-Chronic GvHD: After 3 months: may develop fibrosis additionally, similar to autoimmune disease, usually T cell mediated

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Graft vs Tumor Effect

-beneficial aspect of GvHD, mailnly beneficial in slow progressing disease (chronic leukemia, low-grade lymphoma and some mult myelomas)

-less affective against rapidly progressing: AML