Is the Early Cyclosporine a Level Predictive to the Outcome of Immunosuppressive Therapy in Severe Aplastic Anemia?

Abstract

Although there are many recent studies of efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there has been no study to clarify the correlation between variability of CsA level and the response rate of immunosuppressive therapy (IST). Therefore, we assessed whether the early CsA level would be important or not for IST in acquired severe aplastic anemia (SAA), retrospectively. Thirty one patients were treated with ATG combined with CsA for 6 months. The patient group that achieved higher mean CsA level (≥200 ng/ml, higher CsA group) during first 2 weeks, was shown to more higher response rate than the group, lower mean CsA level (< 200ng/ml, lower CsA group)(response rate of 82.3% in higher CsA group, 21.4% in lower CsA group, p=0.0023). There was also a significant difference in survival rate during median 785 days between higher CsA group and lower CsA group (survival rate of 64.7% in higher CsA group, 28.6% in lower CsA group, p=0.0115). Therefore, we suggest that early higher CsA level during first 2 weeks would be an important factor to achieve the overall response of IST in severe aplastic anemia.

Long‐term follow‐up study of porcine anti‐human thymocyte immunoglobulin therapy combined with cyclosporine for severe aplastic anemia

“…There were no consistent mutations in patients with clonal evolution, and patients with monosomy 7 appeared to be relatively common , but some patients had that abnormality prior to treatment. Our data indicated that PNH evolution was found in 4.9% of patients; however, based on our study and other studies in the literature, PNH evolution can also be found in chronic AA patients receiving CsA treatment alone . There is no evidence that ATG treatment leads to PNH clone amplification .…”

Multivariate logistic analysis of predictors of response to immunosuppressive therapy in children with aplastic anemia: a double-center study

“…In univariate logistic regression analysis, the results showed that interval from symptoms occur to IST <126d, ANC > 0.435 × 10 9 /L, CD4/CD8 < 0.408 and rate of decreased ALC after IST >59.12% were predictive factors of responsiveness to IST. In the study of Moo-Kon Song et al [18], mean CSA levels in 1-2 week after IST >200 ng/mL was associated with higher overall response rate. However, our univariate logistic regression analysis showed that mean CSA level during first to second week of IST more than 207.6 ng/mL was not a positive factor.…”

“…Several factors have been proposed to predict the responsiveness to IST in adult patients with AA, include younger age [12,13], a higher absolute neutrophil count (ANC) [14], a higher absolute reticulocyte count (ARC), a higher actual lymphocyte count (ALC) [15], a higher baseline platelet count [16], a shorter interval between diagnosis and IST [13,17], and higher CSA levels during the 1st-2nd week of IST [18]. However, less data are available from pediatric patients with AA in terms of their responsiveness and risk factors to IST.…”

Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia

“…Several clinical factors have been proposed to predict response and treatment outcomes following IST for SAA. Predictive factors for favorable response to IST include younger age, a higher ANC (9, 10), vSAA (7), a higher ARC, a higher ALC (6), a high inducibility of heat shock protein 72 in peripheral blood mononuclear cells (11), higher CSA levels during the first and second week of IST (12), and the presence of a paroxysmal nocturnal hemoglobinuria clone at baseline (13).…”