Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients Aged ≥60 Years: a Retrospective Study of 629 Patients From the Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC).

Abstract 194

Age has been previously demonstrated to be a major prognostic factor for outcome after allo-SCT. Many centres usually use an age threshold around 50 years for considering a standard myeloablative conditioning regimen, and around 65 years for considering a RIC regimen. The aim of this report was to assess the outcome of 629 patients aged ≥60 years who received RIC allo-SCT, with a special emphasis on the comparison of the outcome of patients aged 60–65 years (y.) and patients aged >65 y.

Between 1998 and 2008, 629 patients with different haematological diseases were treated with RIC allo-SCT, and reported to the SFGM-TC Registry.

This series included 417 males (66%) and 212 females (34%). The median age for the whole cohort was 62 (range, 60–71) y. 378 patients (55%) were diagnosed with a myeloid malignancy, while 240 (38%) had lymphoid malignancies, and 11 (2%) had other non-classifiable diseases. 478 patients (76%) had high risk disease features, and 151 (24%) had a standard risk disease. 386 patients (61%) received allo-SCT from an HLA-matched related donor, while 199 patients (32%) received the graft from a matched-unrelated donor, and 44 (7%) from mismatched donors. Peripheral blood stem cells were used in 83% of patients (n=520). The conditioning regimen consisted of Fludarabine and Busulfan in 280 cases (44.5%), Fludarabine and low dose TBI in 150 cases (24%). The remaining 199 patients (32%) received other so-called RIC protocols.

With a median follow-up of 9 (range, 1–90) months after allo-SCT, grade II-IV and grade III-IV acute GVHD occurred at a median of 31 days after allo-SCT in 29% (n=182) and 12% (n=76) of patients, respectively. Chronic GVHD was observed in 145 patients (23%; limited: n=67; extensive: n=72; unknown stage: n=6). At last follow-up, 347 patients (55%) were still alive (of whom 205 in CR; 65%): 147 patients (16%) died of disease progression, and 180 patients died of transplant-related causes (TRM: 29%). The Kaplan-Meier (KM) estimates of overall survival (OS) at one and 2 years were 57% (95%CI, 53–62%) and 47% (95%CI, 42–52%), respectively.

In order to assess the applicability of RIC allo-SCT to the older age group, we next compared the outcome of patients aged from 60 to 65 y. (n=516) and those aged >65 y. (n=113; median 66 y.; range, 65–71). Except for age, in univariate analysis, these 2 groups were not statistically different in terms of demographic, disease or transplant characteristics. Overall, the median time to ANC>500/μL was 18 (range, 1–102) days, with this being comparable between the younger (60–65 y.) and elderly (>65 y.) age groups (p=0.19). The incidences of grade II-IV and grade III-IV acute GVHD were comparable between both groups (60–65 y.: 29% vs. >=65y.: 30%, p=NS; and 12% vs. 12%; p=NS). The TRM incidence was 29% in the younger group vs. 27% in the older group (p=NS). The KM estimates of OS at 1 and 2 years were 58% (95%CI, 53–62%) and 47% (95%CI, 42–52%) in the younger age group and 55% (95%CI, 44–65%) and 48% (95%CI, 37–60%) in the older age group (p=NS). In a Cox multivariate analysis accounting for all relevant factors, age >65 y. was not found to be a statistically significant factor associated with worsened survival.

Despite its retrospective nature and the inherent selection biases, this data support the use of RIC-allo-SCT in patients >60 y. Moreover, outcome of patients aged >65 y. appears to be comparable to that of patients aged 60–65 y. Physiologic aging is likely more important than chronologic aging. With the refinement of comorbidities scoring systems, age per se (at least up to 70 y.) should not be a contraindication to perform RIC allo-SCT and this should be tested prospectively.