Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia

Abstract

Summary.In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n ¼ 25) or relapse (n ¼ 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0·2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0·2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13 d; P ¼ 0·008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 Ϯ 8% at 10 years. The probability of developing a late clonal disorder was 53 Ϯ 10% after multiple, as compared to 34 Ϯ 7% after single exposure (P ¼ 0·15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.

Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia

“…12 In relapsed SAA, reported response rates with retreatment have been more consistent, approximately 50%-60%. 12,29,30 Unfortunately, the use of more potent immunosuppressive therapy has been controversial because of toxicity 31,32 and the addition of a third drug to horse ATG ϩ cyclosporine has not led to better hematologic recovery or to a decrease in the rate of relapse or clonal evolutions. 33,34 In the present study, we report that alemtuzumab is an effective treatment in SAA, with hematologic recovery in 37% in those patients who were unresponsive to initial horse ATG ϩ cyclosporine and 55% in patients in relapse.…”

Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis

“…This might be due to the high response rate (50-60%) in patients failing or relapsing after first-line treatment. 47,48 As for infections, the guidelines for the diagnosis and management of acquired aplastic anemia published in 2003 recommend considering the use of HGF in patients with severe systemic infections not responding to intravenous antibiotics or antifungals. 5 This issue was not in the frame of our review.…”

Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?

“…This touches on the controversy of over-versus under-treatment, which the authors of the study published in this issue of the journal try to address by following two different CSA tapering schedules. 14 Patients with a full relapse after an initial response have a high rate of response to a second course of ATG [15][16][17] and some patients who have not responded to a first course may respond to a second course. Relapse is re-treatable and does not necessarily confer a bad prognosis.…”