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524 Part VI: The Erythrocyte Chapter 35: Aplastic Anemia: Acquired and Inherited 525

TABLE 35–6. Immunosuppressive Therapy of Aplastic Anemia: Source of Antithymocyte Globulin
Year of Age Range Percent Percent Percent
Report Agents Used No. Pts (years) Response Survival Relapse Comments Citation
2013 H-ATG + CYA 46 14–75 48 @ (NR) 84 @ 5 years 23 @ 3 years H-ATG 174
+GM-CSF 53 15–66 51 @ (NR) 83 @ 5 years 27 @ 3 years & R-ATG
R-ATG +CYA equivalent
2012 R-ATG + CYA + 24 19–81 64 @ 3 70 @ 5 years 28 @ 5 years 170
G-CSF + glucoc months
2012 R-ATG + CYA 46 2-15 85 @ 1 year ?? ?? Pediatric age 172
2012 R-ATG + CYA 35 17–75 60 @ 6 68 @ 27 NR H-ATG better 173
months than R-ATG*
2011 H-ATG + CYA 60 37±3 68 @ 6 96 @ 3 years NR H-ATG better 169
R-ATG + CYA 60 31±3 months 76 @ 3 years than R-ATG
37 @ 6
months
2011 R-ATG + CYA + 20 19–80 50 @ 1 years 65 @ 3 years NR ?R-ATG simi- 171
glucoc lar to H-ATG*
2010 H-ATG 42 1–66 59 @ 6 78 @ 2 years NR H-ATG better 167
R-ATG 29 4–63 months 55 @ 2 years than R-ATG
34 @ 6
months
2009 R-ATG + CYA + 13 20–83 92 @ 1y NR 30 @ 18 ?R-ATG 168
G-CSF months better than
H-ATG*
2006 H-ATG +CYA 30 2–71 73 @ (NR) 80 @ 5 years NR H-ATG better 166
+GM-CSF +EPO 32 2–71 53 @ (NR) 66 @ 5 years NR than R-ATG
R-ATG +CYA
+GM-CSF +EPO
CYA, cyclosporine; EPO, erythropoietin; Glucoc, glucocorticoids; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-monocyte,
colony-stimulating factor; H-ATG, horse antithymocyte globulin; No., number; NR, not reported; Pts, patients; R-ATG, rabbit antithymocyte
globulin.
*Based on prior studies of H-ATG.

either (1) primary treatment, 185–188 (2) in patients refractory to ATG or crossover study of newly diagnosed patients, survival of approximately
glucocorticoids, 186–191 (3) in combination with G-CSFs, 192,193 or (4) in 65 percent was observed 12 months after diagnosis.
varying combinations with other modes of therapy. Cyclosporine is Combination Immunotherapy Combination treatment of
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administered orally at 10 to 12 mg/kg per day for at least 4 to 6 months. severe aplastic anemia usually includes, for example, ATG, 40 mg/kg
Dosage adjustments may be required to maintain trough blood levels per day, for 4 days; cyclosporine, 10 to 12 mg/kg per day, for 6 months
of 200 to 400 ng/mL. Renal impairment is common and may require and methylprednisolone, 1 mg/kg per day, for 2 weeks. The dose of
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increased hydration or dose adjustments to keep creatinine values cyclosporine is adjusted to maintain a trough level of 200 to 400 ng/
below 2 mg/dL. Cyclosporine also may cause moderate hypertension, mL. Prophylaxis for Pneumocystis carinii with daily trimethoprim-
a variety of neurologic manifestations, and other side effects. Several sulfamethoxazole or with monthly pentamidine inhalations should
drug classes interact with cyclosporine to either increase (e.g., some be considered for these patients as they receive immunosuppressive
antibiotics and antifungals) or decrease (e.g., some anticonvulsants) therapy.
blood levels. Responses usually are seen by 3 months and may range The addition of cyclosporine to the combination of ALG and glu-
from achieving transfusion independence to complete remission. cocorticoids improves response rates to approximately 70 percent of
Approximately 25 percent of patients respond to this agent when used patients (Table 35–7). 197,198 G-CSF added to the combined immunosup-
alone, but the response rate has ranged from 0 to 80 percent in various pressive therapy does not increase response rate or survival. Response
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reports. 194 is usually defined as a significant improvement in red cells, white cells,
Although immunosuppression with ALG or ATG has been used and platelets to eliminate risk of infection and bleeding and the require-
the longest and has a seemingly better response rate, there are certain ment for red cell transfusions.
advantages to cyclosporine. This drug does not require hospitaliza- The 5-year survival after completion of combination immuno-
tion or use of a central venous catheter. Fewer platelet transfusions are suppressive therapy may approximate that after stem cell transplan-
required during the first few weeks of therapy compared to treatment tation. Forty-eight children treated between 1983 and 1992 had a
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with ALG or ATG. A French cooperative trial showed equal effec- 10-year survival of approximately 75 percent for marrow transplanta-
tiveness of cyclosporine compared to ATG plus prednisone. In this tion and approximately 75 percent for combined immunosuppressive
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