Rabbit antithymocyte globulin (r‐ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy

Abstract

Summary. About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2±67) not responding to a ®rst course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3´5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 mg/kg subcutaneously from day 1 to 90). The median interval between ®rst and second treatment was 151 d (range 58±361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, de®ned as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14±377). Nine patients (30%) achieved complete remission (neutrophils >2´0´10 9 /l, haemoglobin >11 g/dl and platelets >100´10 9 /l). The overall survival rate was 93% with a median follow-up of 914 d (range 121±2278). So far, no patient has relapsed. Female gender was signi®cantly associated with a poorer likelihood to respond (P 0´0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to ®rst-line IS treatment.

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

“…7 While hATG has been the primary treatment used for severe AA, patients with relapsing or refractory AA often receive rATG after a first course of hATG. Although initially reported response rates in this setting approached 77%, 12 responses in subsequent studies were more modest, at 30% in hATG-refractory patients and 65% in relapsed primary responders. 13 Only limited efficacy data are available for rATG used as initial therapy in severe AA.…”

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.…”

“…In the USA the horse product is still available (ATGAM ® ) while in Europe horse ATG (Lymphoglobulin ® ) has been withdrawn in favor of a rabbit ATG (Thymoglobulin ® ) which is dosed differently and which has not been well documented as being efficacious as first-line therapy for severe aplastic anemia. 17 A third ATG, also of rabbit origin, is available: this form is produced not by sensitizing with human thymocytes but a T-acute lymphocytic leukemia cell line i.e. Jurkat cells.…”

Treatment strategies for patients with severe aplastic anemia

“…This can rescue a significant proportion of nonresponders. 20 Relapse of cytopenia is an additional problem, 21 and requires very slow tapering of CsA: some patients, however, become CsA dependent.…”