Hematopietic Cell Transplantation after a Low-Dose, Total-Body Irradiation Based Regimen in Elderly Patients with AML: A Multicenter, Multinational, Prospective HOVON/SAKK/OSHO Study.

Despite reaching initial CR, most elderly AML patients relapse within 2 years of diagnosis and die within 3 years. Following favourable feasibility and phase II studies, we have investigated the role of allogeneic HCT after low dose TBI as consolidation therapy in these patients. Patients were included within the OSHO and HOVON/SAKK protocols and, upon attaining CR1, were treated after the induction and first consolidation in the OSHO protocol and after the second induction cycle in the HOVON/SAKK protocol. Patients received allogeneic, related HCT whenever a family donor was available. Dedicated HOVON/SAKK and OSHO centers used unrelated HCT in patients lacking a family donor. Between May 7, 2002 and August 15, 2005 a total of 83 patients with a median age of 62 (range 40–74) years received low dose TBI based preparative regimens followed by related (n=54) or unrelated (n=29) HCT. There was no difference in age between patients with related (median 63, range 51–74 years) and unrelated grafts (median 61, range 40–72 years), but secondary AML was more frequent in those receiving unrelated HCT (46%) compared to related HCT (15%). The interval from start of the last chemotherapy to HCT was median 80 (36–206) days and 74 (46–184) days for related and unrelated HCT respectively (p=0.46).

Results: Absolute neutrophil counts remained above 500μL⁻¹ in 25% of the patients. A median of 0 (range 0–48) and 0 (range 0–14) units of packed red cells and platelets were required. Six patients (7%) rejected. Acute GvHD grades II–IV was diagnosed in 22% and chronic GvHD at 2 years in 23% of the patients. A total of 18 patients received donor lymphocyte transfusions either for relapse (n=13) or for mixed chimerism/graft rejection. OS at 2 years was 51±7% following related- and 65±0.10% following unrelated-HCT. Similarly, DFS was 39±7% and 54±10% for patients with related and unrelated donors respectively. As in previous protocols, the non-relapse mortality amounted to 22±7% for related and 17±9% for unrelated HCT. The major reason for failure was a RI of 50±9% and 35±10% for related and unrelated HCT respectively. Median follow up reached 22 (range 10–41) months. Age < or >60 years did not influence survival (OS median 54± 7% vs, 59± 10% and DFS 43± 8% vs. 47 ± 10% for ≥ 60 yrs and <60 yrs respectively; p=0.82). Results of patients over ≥ 60 yrs (n=55) were compared to patients ≥ 60 yrs with intermediate and high risk cytogenetics who were treated in the OSHO protocol during the complete study period (n=103), but who received a second consolidation with chemotherapy. The OS at 3 years was 54.0± 7% for the HCT arm and 41.0± 5% for the chemotherapy arm.

Conclusions: These results confirm those of a phase II study on referred patients with AML at different stages of disease. Since patients have been entered from diagnosis, comparison with patients receiving chemotherapy as second consolidation, was performed. OS at 3 years was higher in patients receiving HCT than in those receiving chemotherapy.