Abstract

Abstract 3194

Poster Board III-131

Background

Immunosuppressive therapy (IST) is considered to be the first-line treatment in patients with severe aplastic anemia (AA) who are not eligible for hematopoietic stem cell transplantation (HSCT). Most IST schemes are based on the combination of anti-thymocyte globulin (ATG) plus cyclosporine A (CsA). Differently from other countries, two ATGs have been approved in Spain for AA from 2003 to 2007: Lymphoglobuline (LG) (raised in the sera of horses) and Thymoglobuline (TG) (produced in rabbits). So, during this period of time, the standard therapeutic protocol of the Spanish study group for AA included both options, and the physicians chose LG or TG based on their own wishes. Most published studies in AA are with LG, which is no longer manufactured. Recent limited data have confirmed therapeutic efficacy of TG, but no randomized studies have been performed comparing both products' activity. The aim of this report is to communicate the outcomes of a group of patients with AA who received either a LG- or TG-based scheme as first-line treatment.

Patients and methods

we retrospectively investigated the outcome of 110 patients with AA treated with IST at front line between 2003 and 2008. Thirty-five patients (32%) got LG (15 mg/kg/day/x5 days), and 75 patients (68%) got TG (2.5 mg/kg/day/x5 days). All patients also received methylprednisolone and CsA. Response rate (RR) was assessed at post-IST day +90, day +180, and day +365. If complete response (CR) was not reached, patients received a second course of IST, a second-line therapy (HSCT or androgens), or no treatment. When a second course of IST was employed, it included LG at the same dose as in the first course (15 mg/kg/day/x5 days), or TG at a higher dose (3.5 mg/kg/day/x5 days). CR was defined as a neutrophil count >1.5×109/L, a platelet count >100 ×109/L, and a hemoglobin level >120 g/L. Partial response (PR) was defined as a neutrophil count >0.5×109/L, a platelet count >20 ×109/L, and a hemoglobin level >80 g/L. Subgroup analyses were conducted and differences in response were tested using the chi-square statistic test.

Results

After the first course of IST, CR was achieved in 31 patients (28%) (group A), and PR in 20 patients (18%). Overall response (OR) was similar for both globulins (LG: 49%, TG: 45%). Thirty-five of the patients who did not reach CR after the first IST course, received a second course of IST (6 with LG and 29 with TG) (group B), and 44 patients underwent a different approach (second-line therapy or no treatment) (group C). After the second course of IST, 14 patients achieved CR (40%) and 11 patients PR (31%). OR was similar for LG (67%) and TG (72%). If we exclude patients in group C, the RR among the remaining 66 patients (who underwent 1 or 2 courses of IST) was 85% (68% CR, and 17% PR). No major drug-related toxicities were reported in the whole group of patients.

Conclusions

ATG-based schemes with both LG and TG were well tolerated as treatment of patients with AA. OR after first course of IST was similar in the LG and in the TG group (49% versus 45%). RR after second course of IST was also similar when LG and TG were employed (67% versus 72%). After excluding those patients who, not having reached CR after the first course, underwent an approach different from a second course of IST, RR to IST was 85%, with 68% of CR. No statistical differences were found based on the type of ATG administered. The results of this study show that TG is, at least, as effective as LG for the treatment of AA patients. Based on these and other recently published data, the current standard therapeutic protocol of the Spanish study group for AA includes TG at the dose of 3.75 mg/kg/day/x5 days for both the first and, if necessary, second course of IST. To our knowledge, no reports are available in the medical literature comparing the outcome of patients with AA who received LG or TG as the first-line therapy for AA. So, in spite of the fact that our study is retrospective and not randomized, we think our data are unique and very useful for helping physicians in switching from LG to TG.

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.