Treosulfan, Etoposide and Cyclophosphamide as Non TBI-Conditioning Regimen Followed by Allogeneic SCT for Acute Lymphoblastic Leukemia

Abstract 1327

Total body irradiation (TBI) is an essential part of the conditioning regimen for acute lymphablastic leukaemia (ALL) patients who undergo allogeneic stem cell transplantation. Due to high toxicity and mortality induced by TBI, we investigate in a multicenter prospective phase II study the toxicity and efficacy of a non TBI-based regimen consisting of treosulfan (3 × 12 g/m²), etoposide (30 mg/kg), and cyclophosphamide (120 mg/kg) in patients with ALL who underwent allogeneic stem cell transplantation. Major inclusion criteria were complete remission, indication for allogeneic stem cell transplantation according GMALL, non eligibility for TBI or patient's wish to avoid TBI. Graft-versus host prophylaxis consisted of cyclosporine A and short course methotrexat and in case of unrelated donors also of anti-lymphocyte globulin (ATG). This preliminary analysis is based on 36 patients (female: n=17; male: n=19) with a median age of 42 years (range: 18–60y). Remission-status at transplantation was either 1. CR (n=27), 2.CR (n=7) or >2.CR (n=2). Donors were HLA-identical sibling (n=6), matched unrelated (n=21) or mismatched unrelated (n=9). 39% of the patients were Philadelphia chromosome positive. Primary graft failure was observed in 1 pts. The median time to achieve leukocyte (> 1×10⁹/l)) and platelet (>20 × 10⁹/l) engraftment was 22 (range, 11–47) and 24 days (range, 11–95), respectively. The toxicity was moderate including VOD (6%) and liver toxicity grade III (8%) and IV (3%). Acute graft versus host disease grade II-IV and grade III/IV was noted in 22% and 11%, respectively. Chronic graft versus host disease at 1 year was seen in 27%, which was extensive in 7% of the patients. After a median follow up of 12 months, the cumulative incidence of non-relapse mortality (NRM) at 1 year was only 9% (90% CI: 1–17%) and for relapse 37% (90% CI: 21–52%). The estimated 1-year disease free survival was 56% (90% CI:40-71%) and significantly better for patients transplanted in 1.CR vs 2. or higher CR (68% vs 15%, p=0.05). The estimated 1-year overall survival was 81% (90% CI: 69–92%). This preliminary results of a treosulfan, non TBI based conditioning regimen followed by allogeneic stem cell transplantation shows favourable toxicity profile with low non-relapse mortality. Longer follow up is needed to determine long-term freedom from disease.