Treatment of 287 Patients(pts) with Severe Aplastic Anemia(SAA) Using Cyclosporine-A(Csa) and Prednisone(Pred): 15 Year Follow-Up from a Single Instituition.
Authors: Bitencourt Marco A. , Bonfim Carmem M.S. , Ruiz Jefferson , Setubal Daniela C. , Funke Vaneuza M. , Zanis-Neto Jose , deMedeiros Carlos R. , Pasquini Ricardo 
Published: April 2020

Introduction: Allogeneic Stem Cell transplantation from an HLA identical sibling is considered the treatment of choice for young pts. For pts without a suitable donor, immunosupressive treatment with cyclosporine (Csa) + prednisone (Pred) + Antithymocyte globulin (ATG) is an effective alternative treatment. In 1988, as ATG supply was not regular in our country, we decided to initiate a trial using only Csa +Pred to treat SAA without a matched sibling donor.

Material and Methods: All pts had the diagnosis of SAA according to established criteria (Camitta et al Blood1976; 48:63–70) and 95 pts had received previous treatment (androgens, Csa alone or steroids). Treatment: Csa: 12mg/kg/day BID from day(D)1- D8, then 7mg/kg/day BID until 1 year. After 1 year, Csa was slowly weaned (5% each month) until definitively stopped. Csa levels were maintained between 200-400ng/ml. Pred:2mg/kg/day from D1-D14 then 1mg/kg/day from D15- D45. From that day on Pred dose was weaned 20% each week until stopped. Prophylactic antibiotics were given according to common practice. Number of pts: 287. Period: 12/1988 to 01/2004. Age: 2-74y (Median: 22). Disease duration: 10–4015days (Median:100). Previous transfusions: 0-160UI (M:10). At diagnosis, granulocytes counts ranged from 0-3110/ul(M:540/uL) and platelet counts from 1000-53000/uL(M:11000/uL). Treatment evaluation was performed at 6weeks, 3,6 and 12 months and then yearly after. Definition of response: Type I: independence of red cells and platelets transfusions and improvement of hematological parameters (Hb&gt;10g/dL, platelets&gt;50.000/uL and granulocytes&gt;1000/uL). Type II: Improvement of hematological parameters (not enough to reach the hematological counts previously specified) with or without dependence of blood transfusions. Type III: No evidence of improvement and dependence of blood transfusions.

Results: Overall survival is 63% with a median follow-up of 7 y(6months- 15 years). Response to treatment: TypeI was achieved in 138pts (48%) and all but one pt is alive. These pts have a normal life, free of infections and are transfusion independent. TypeII occurred in 21 pts(7,3%) and 13 pts are alive with only 1 pt dependant of red blood cell transfusions every 45 days. TypeIII occurred in 128pts (44%) and 50 pts are still alive. Most pts responded between 3 and 6m of treatment. Response to treatment was significantly influenced by: Granulocytes at diagnosis &gt;500/uL (p=0,0001); platelets at diagnosis &gt;12000/ul (p=0,01); age&gt;22y(p=0,0061) and previous transfusions &lt; 10UI (p=0,008). Granulocytes at diagnosis &gt;500/uL (p=0,02), platelets at diagnosis &gt;10000/uL (p=0,01)and disease duration &gt;45 days (p=0,02) significantly affected survival. Toxicity was tolerated and well controlled. Hypertension, gingival hypertrophy and diabetes mellitus were frequent complications. Relapse occurred in 19% (31pts) and twenty-two pts(70%) responded to a second treatment using the same drugs but 9pts became cyclosporine dependant. Clonal or malignant disease occurred in 5 pts (2AML and 3 PNH).

Conclusion: This data demonstrates that Csa +Pred is an effective treatment for pts with SAA without a suitable donor. Pts may become free of infections and transfusion independent and are able to live normal lives even though their blood counts are still subnormal