Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia

Abstract

Horse anti-thymocyte globulin (h-ATG) and ciclosporin are the initial therapy for most patients with severe aplastic anaemia (SAA), but there is no practical and reliable method to predict response to this treatment. To determine whether pretreatment blood counts discriminate patients with SAA who have a higher likelihood of haematological response at 6 months to immunosuppressive therapy (IST), we conducted a single institution retrospective analysis on 316 SAA patients treated with h-ATG-based IST from 1989 to 2005. In multivariate analysis, younger age, higher baseline absolute reticulocyte count (ARC), and absolute lymphocyte count (ALC) were highly predictive of response at 6 months. Patients with baseline ARC > or = 25 x 10(9)/l and ALC > or = 1 x 10(9)/l had a much greater probability of response at 6 months following IST compared to those with lower ARC and ALC (83% vs. 41%, respectively; P < 0.001). This higher likelihood of response translated to greater rate of 5-year survival in patients in the high ARC/ALC group (92%) compared to those with a low ARC/ALC (53%). In the era of IST, the baseline ARC and ALC together serve as a simple predictor of response following IST, which should guide in risk stratification among patients with SAA.

Figure 1

Baseline peripheral blood count values are plotted against the estimated probability of response based on univariate logistic regression. A positive correlation was observed between the absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), absolute neutrophil count (ANC) and response at 6 months. There was no significant correlation between the baseline platelet count or the PNH clone size and response. Age correlated inversely with the probability of response at 6 months. The vertical bars “|” represent the covariate values (jittered for PNH to separate multiple subjects with the same values) for responders (top) and nonresponders (bottom). The dotted lines represent the 95% pointwise confidence intervals.

Figure 2

Survival probability in all patients with a high baseline absolute reticulocyte count (ARC), low ARC and a high absolute lymphocyte count (ALC), and a low ARC and ALC (× 10⁹ /l). Those who underwent haematopoietic stem cell transplantation were censored at the time of transplant.

Figure 3

Survival probability in children less than 18 years (N=77) according to baseline ARC (× 10⁹ /l) with haematopoietic stem cell transplantation (HSCT) censored (3A) and not censored (3C). Survival probability in adults only (N=239) according to baseline ARC and ALC (× 10⁹ /l) with HSCT censored (3B) and not censored (3D).