Allogeneic Stem Cell Transplantation from Matched Related Donor in Patients Over the Age of 55 Years After Reduced Intensity Conditioning Associating Fludarabine-Iv Busulfan and Rabbit-Antithymocyte Globulin: A Prospective Multicenter Phase II Clinical Trial with Socio Economic Evaluation

We prospectively assess, in pts over 55 years, eligible for an matched sibling Allo-SCT, the impact of a RIC with Fludarabine (30 mg/m2/day (D-5 to D-1)), IV Busulfan (0.8 mg/kg x 4/day (D-4 to D-3)) and r-ATG (2.5 mg/kg/day (D-2 to D-1). Eventually, from 03/07 to 06/10, 82 pts have been included, of which 79 have been transplanted. Median follow-up is 24 months (10-50). All grafts were PBSC from a HLA identical sibling. CSA (2 mg/kg) was started on day -2. Median age is 60 (55-70). Karnofsky score was 90 (60-90). Diagnoses: AML = 32; MDS = 13; ALL = 6; NHL = 10; MM = 13; Others = 5); 54 pts were in CR (CR1 = 31; CR2 = 15; CR>2 = 8), 22 in PR or SD and 3 in PD after a median of 2 (1-7) lines of chemotherapy. All pts engrafted and 46 presented with aGVHD (G1 n = 32; G2: n = 7; G3-4: n = 6) for a 17% (10-23) cumulative incidence of G≥ 2 aGVHD. A total of 47 pts had cGVHD (Limited: N = 28; extensive: N = 19) at a median of 4.5 months (3-21) for a one year overall and extensive cumulative incidence of 57% (46-68) and 34% (25-45) respectively. 12 pts died from NRM. The 6 month and overall cumulative incidences of NRM were 5% (0-10) and 16% (9-23) respectively. Karnofsky score was not predictive of NRM. 25 pts relapsed at a median of 4.2 months (0.8-12) for a cumulative incidence of 32% (23-42). Relapse incidence differed according to disease pre-transplant status (9 of 46 CR1/CR2 vs. 16 of 33 beyond CR2 pts; p = 0.008). Three year overall and disease-free survival probabilities were 79% (67-87) and 59% (45-71) respectively. Considering the CR1 AML population (N = 21), median age was 61 years (56-70) and probabilities of NRM, relapse, OS and LFS were 14% (IC95 = 0-27), 14% (IC95 = 2-26), 72% (IC95 = 47-86) and 67 % (IC95 = 43-83) respectively. Economic data covering transplant and first 18 month post-transplant periods have been prospectively collected and are under analysis. HRQL (Health Related Quality of Life) was assessed over a 1-year period with the EORTC QLQ-C30 questionnaire (Days -7, +80, +180, +360). The lowest functioning scores and highest symptom scores were experienced 80 days after transplantation. Thereafter the level of functioning and level of symptoms returned to baseline levels, which is reassuring in this population. Taking account patient characteristics, results confirm that Allo-SCT after RIC is a valid option in this population, that RI. Further refining of this association, by cautious tuning of the IV Busulfan dose, is under process in our program.