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Aplastic Anemia
Aplastic anemia is a bone marrow failure syndrome characterized by peripheral pancytopenia and marrow hypoplasia.
Bone marrow failure is a term with a larger meaning, referring to disorders of the hematopoietic stem cell which involves either one cell line or all of the myeloid cell lines
Acquired:
1. Drugs
- Cytotoxic drugs - Antibiotics - Chloramphenicol - Anti-inflammatory - Anti-convulsant - Sulphonamides - 2-3 months usually between exposure and the development of aplastic anemia.
Important clinically in patients with hemolytic anemias 5-10% of cases of AA in the West and 10-20% in the Far East. 2-3 months between exposure to the virus and the development of AA.
Absent or defective stem cells (stem cell failure). Abnormal marrow micro-environment. Inhibition by an abnormal clone of hemopoietic cells. Abnormal regulatory cells or factors. Immune mediated suppression of hematopoiesis.
It is believed that genetic factors play a role. There is a higher incidence with HLA (11) histo comp. Antigen. Immune mechanism is involved.
Inevitable:
dose related e.g. cytotoxic drugs, ionizing radiation. The timing, duration of aplasia and recovery depend on the dose. Recovery is usual except with whole body irradiation.
Idiosyncratic:
unpredictable to drugs e.g., anti-inflammatory antibiotics, anti-epileptic, these agents usually do not produce marrow failure in the majority of persons exposed to these agents.
Transition to a clonal disorder of hemopoiesis can occur in any patient who has recovered bone marrow function, suggesting that fragility of the hemopoietic system is common to all forms of aplasia.
BM Aspiration
BM Biopsy
Hemoglobin electrophoresis may show elevated fetal hemoglobin. Biochemical profile, including evaluation of transaminases, bilirubin, lactic dehydrogenase, Coombs test, and kidney function, is useful in evaluating etiology and differential diagnosis. Serologic testing for hepatitis EBV, CMV, and HIV Autoimmune disease evaluation for evidence of collagenvascular disease The Ham test or sucrose hemolysis test frequently is performed for excluding PNH. Histocompatibility testing should be conducted early to establish potential related donors, especially in younger patients.
Causes of pancytopenia
1.Failure of production of blood cells
a) bone marrow infiltration - acute leukemias - hairy cell leukemia - multiple myeloma - lymphoma - myelofibrosis - metastatic carcinoma b) aplastic anemia
2. Ineffective hematopoesis
- myelodysplastic syndrome - vit.B12 and folate deficiency
2. Restrictions
- age below 40 - suitable donor available in less than 30% (sibling) - 25-40% risk of GVHD - 5-15% risk of graft failure in multitransfused patients - high mortality after MUD-HSCT - solid tumors (12%)
Immunosuppressive therapy
Indicated for patients > 40 years Patients with no HLA matched sibling donors. Anti-Thymocyte Globulin(ATG) or antilymphocyte globulin (ALG), cyclosporin, methylprednisolone. Best results are for combination therapy. Response is slow, 4-12 weeks to see early improvement.
Immunosuppressive therapy
Immunosuppressive therapy
Antithymocyte globulin, equine (Atgam) - 10-20 mg/kg/day for 8-14 days. Antithymocyte globulin, rabbit (Thymoglobulin) - 0,75 mg/kg/day for 8 days. Cyclosporine (Sandimmune, Neoral) - 1.5-2 mg/kg IV q12h, Methylprednisolone (Medrol, Solu-Medrol) - :5 mg/kg IV on days 1-8; then tapered using PO 1 mg/kg on days 9-14; further tapering over days 15-29. Stop after 1 mo except in evidence of serum sickness. Cyclophosphamide (Cytoxan) : 45 mg/kg/d IV for 4 d.
Immunosuppressive therapy 2
Response rates 60-70% Relapses are common and continued supportive care needed. Up to 50% of relapsed patients will respond to 2nd course of immunosuppressive therapy.
Hematopoietic growth factors - G-CSF and GM-CSF, may be useful in patients with neutropenia who have infections, without requiring a WBC transfusion.