3.26 GOORHA BM Failure/Hematopoietic Stem Cell Transplants

Question 1

BM Failure

Answer 1

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

Question 2

Aplastic Anemia

Answer 2

• Typically younger patients
• Peripheral pancytopenia and hypocellular BM
• Path: reduction or depletion of hematopoietic precursor stem cells with decreased production of cell lines

Question 3

Aplastic Anemia: Congenital

Answer 3

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

Question 4

Aplastic Anemia: Aquired

Answer 4

• 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

Question 5

Aplastic Anemia Lab Findings

Answer 5

• 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

Question 6

Treatment of Aplastic Anemia

Answer 6

• Supportive care (transfusions, abs)
• Immunosuppressive regimens: shown to improve count (points to auto immuno for idiopathic cause) Hematopoietic cell transplantation (HSCT)

Question 7

Pure Red Cell Aplasia

Answer 7

• 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

Question 8

Myelodysplastic Syndromes

Answer 8

• 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

Question 9

MDS vs Aplastic Anemia

Answer 9

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

Question 10

MDS Treatment

Answer 10

• 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

Question 11

HSCT

Answer 11

• 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)

Question 12

Autologous HSCT

Answer 12

• 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

Question 13

HSCT Allogenic

Answer 13

• 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

Question 14

Types of Allogenic HSCT

Answer 14

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)

Question 15

Complications of Allogenic HSCT

Answer 15

• 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

Question 16

Graft vs Tumor Effect

Answer 16

• 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