Aplastic Anemia: A Retrospective Review of Outcomes after Prolonged-Duration Calcineurin Inhibitor-Based Immunosuppression

Abstract Introduction: Solid organ transplant recipients may receive calcineurin inhibitor therapy for years without lethal consequences. Severe aplastic anemia is a cellular immunological rejection of hematopoiesis that is amenable to calcineurin-based immunosuppressive therapy. A general guideline exists to discontinue immuno-suppressive therapy following a complete response or after 4-6 months, despite a relapse rate of 30-50% and often less than optimal choices for second-line treatment. Anecdotal conversions from late and/or lengthy partial remissions to complete responses prompted this single-institutional retrospective analysis of patients who received extended calcineurin inhibition (ECI). Objective: To assess outcomes of extended cyclosporine therapy (greater than six months) in patients with aplastic anemia with one of the following circumstances: (1) no matched sibling bone marrow donor; (2) relative contraindication to a second course of intensive immunosuppressive therapy; or, (3) not able to access a promising investigational protocol. Design, Setting, and Patients: Fifty patients with severe aplastic anemia treated at Indiana University Melvin and Bren Simon Cancer Center between 1994 and 2014 were screened. Treatment groups included extended calcineurin inhibitor (n=16) and matched sibling-donor (MRD) bone marrow transplantation (BMT, n=9). Patients who received matched unrelated (MUD) BMT or supportive care or those with missing data were excluded from analysis. Methods: After an initial treatment with anti-thymocyte globulin, glucocortico-steroids and calcineurin inhibition, patients who received MRD-BMT were compared to those who received ECI. Changes in hemoglobin (Hb), white blood cell (WBC) and platelet (Plt) counts were monitored and survival rates were analyzed for the two groups. Results: Median follow-up was 93 months. Table 1 describes improvements in cell counts with ECI and BMT over 6 months, 12 months, 24 months and 36 months. Survival for ECI group was 87.5% versus 88.9% for patients undergoing BMT, p-value 0.759. Conclusion: Patients with severe aplastic anemia who received MRD-BMT had a more rapid improvement in Hb, WBC and plt counts compared to those who received ECI. However, the difference of improvement in Hb, WBC and plt counts at 36 months and survival between these two groups was not statistically different. Table 1: . ECI BMT p-value WBC Improvement at 6 months 1.1 k/cumm 1.5 k/cumm 0.629 WBC Improvement at 12 months 0.9 k/cumm 2.9 k/cumm 0.034 WBC Improvement at 24 months 1.0 k/cumm 3.0 k/cumm 0.023 WBC Improvement at 36 months 1.8 k/cumm 3.2 k/cumm 0.289 Hb Improvement at 6 months 2.0 GM/dl 5.8 GM/dl 0.002 Hb Improvement at 12 months 2.0 GM/dl 6.8 GM/dl 0.001 Hb Improvement at 24 months 2.5 GM/dl 7.1 GM/dl 0.012 Hb Improvement at 36 months 3.3 GM/dl 7.0 GM/dl 0.130 Plt improvement at 6 months 25 k/cumm 151 k/cumm 0.001 Plt improvement at 12 months 37 k/cumm 172 k/cumm 0.007 Plt improvement at 24 months 45 k/cumm 164 k/cumm 0.010 Plt improvement at 36 months 54 k/cumm 167 k/cumm 0.078 Disclosures No relevant conflicts of interest to declare.