A Pilot Trial of Two Dose Levels of Rabbit Antithymocyte Globulin, (rATG), Thymoglobulin, as Part of a Myeloablative-Conditioning for a HLA Identical Matched Related Donor Stem Cell Transplant (SCT) with Cyclosporine (CsA) as Graft Versus Host Disease (GvHD) Prophylaxis.

To determine the role of rATG to modify the development of acute GvHD we conducted a randomized, prospective, open-label, multi-center pilot study in patients with ALL or AML in first or second remission. CsA was the only agent used for GvHD prophylaxis. Patients (N=22) were randomized (1:1) to receive either 4.5 mg/kg or 8.5 mg/kg of ATG during the preparative regimen. The rATG infusions were completed on Day -1, within 18 hours prior to SCT on Day 0. The low (N=11) and high dose groups (N=11) were comparable for age, diagnosis and remission status. The mean age was 41.4 and 39.6 years in the low and high dose groups respectively. In both groups 6/11 patients had AML and 5/11 had ALL. All patients received a fully ablative preparative regimen from a HLA matched related donor.

Results: Mean time to neutrophil engraftment was 6.5 and 7.3 days for the low and high dose arms, respectively. The incidence of Grade > II acute GvHD was 0/11 for the low dose arm and 3/11 for the high dose arm. Infections were seen in 9/11 patients in both groups. The cumulative number of hospitalization days was 30.4 and 47.6 days (p=n.s.) in the low and high dose groups respectively. The overall survival at 180 days was 63.6 % in the low dose group and 54.5 % in the high dose group (p=n.s.). The disease free survival (DFS) at day 180 was 54.5% in both groups. The treatment related mortality (TRM) was 18.2 % in the low dose and 45.5 % in the high dose (p=n.s.) The relapse rate was 18.2 % in the low dose group and 0% in the high dose group (p=n.s).

Conclusion: This pilot study suggests that rATG may modify the development of serious acute GvHD in patients who received a fully ablative SCT. The low, combined, 3/22, incidence of acute GvHD (13.6%) in patients who received rATG(Thymoglobulin) and post transplant CsA suggests that this combination is an acceptable regiment for GvHD prophylaxis. The lower dose of rATG, 4.5 mg/kg, was as effective and was associated with a lower TRM as compared to the higher, 8.5mg/kg dose. The use of rATG administered during the preparative regimen was well tolerated and may provide an effective alternative to methotrexate when used as part of an ablative conditioning regimen in HLA identical related donor SCT.