Predicting Response and Survival for Severe Aplastic Anemia Patients Treated with Immunosuppression.

Prognosis in acquired aplastic anemia is predicted by blood counts. The popular “Camitta criteria” were developed about 40 years ago, prior to the introduction of immunosuppressive therapies (IST) and the wide application of hematopoietic stem cell transplantation (HSCT), both of which have markedly improved survival in bone marrow failure. The hematologic response rate to anti-thymocyte-globulin (ATG) has been reported by many centers to be 60–70%; however, a practical and reliable predictor of response to IST is not available. Therefore, the decision to pursue HSCT or IST in SAA often relies on the patient’s age, availability of an HLA-matched sibling donor and in the presence of comorbidities. We conducted a retrospective analysis of 316 patients who received initial IST with a horse ATG-based regimen at the NIH Clinical Center from 1989 to 2005 for criteria that were predictive of hematologic response at 6 months and survival long-term. In multivariate analysis, younger age and higher baseline absolute reticulocyte count (ARC) and absolute lymphocyte count (ALC) were predictive of response at 6 months. Patients with a baseline ARC ≥ 25,000/uL (96 patients) had a much greater probability of response at 6 months following IST compared to the 91 patients with an ARC < 25,000/uL and an ALC < 1,000/uL (80% vs. 41%, respectively; p < 0.001). Those with an ARC < 25,000/uL and an ALC ≥ 1,000/uL (129 patients) formed an intermediate risk group with a probability of response to IST of 62%. This higher likelihood of response translated to better survival in patients in the high ARC and ALC group (92% at 5 years) compared to those with a low ARC and ALC (53%). The probability of response in patients younger than 18 years of age was 74% regardless of the pre-treatment blood counts. When the predictive criteria of the ARC and ALC was used in pediatrics patients only, the ALC was not predictive, however a high baseline ARC remained a significant predictor of response in the pediatric cohort with a response rate of 90% (in those with an ARC ≥ 25,000/uL) vs. 65% (in those with an ARC < 25,000/uL; p=0.02). In the post-ATG era, baseline ARC and ALC together serve as simple predictor of response following IST, which should guide in stratifying risk among patients with SAA. These criteria should be useful for comparison between studies and in clinical decision making, particularly regarding timing of transplantation, as the indication for matched sibling HSCT (now offered to older patients) and alternative donor HSCT (in patients who lack an HLA-matched sibling) broadens.