Autologous Hematopoietic Cell Transplantation in Elderly Patients Aged 65 and Older: A Retrospective Analysis By the Complications and Quality of Life Working Party of the EBMT
Authors: Sánchez-Ortega Isabel , Basak Grzegorz W. , Beohou Eric , van der Werf Steffie , Labopin Myriam , van Biezen Anja , Kroeger Nicolaus , Montoto Silvia , Nagler Arnon , Dreger Peter , Goldschmidt Hartmut , Blaise Didier , Einsele Hermann , Finke Jürgen , Russell Nigel H , Haenel Mathias , Potter Michael , Caillot Denis , Salwender Hans-Juergen , Ljungman Per T. , Craddock Charles , Garderet Laurent , Sureda Anna , Mohty Mohamad , Ruutu Tapani , Duarte Rafael F. 
Published: October 2019

Abstract
INTRODUCTION: Age is no longer a barrier to successful autologous hematopoietic cell transplantation (autoHCT). Improved stem cell mobilization and supportive care are potentially making autoHCT more feasible in elderly patients in recent years. However, reports of autoHCT outcomes in elderly patients aged 65 years-old (yo) and older are limited. These patients are underrepresented in clinical trials and data usually come from relatively small series and subgroup analyses in the main indications, namely multiple myeloma (MM) and lymphoproliferative disorders (LPD). Here, we sought to evaluate the feasibility and general outcomes of the autoHCT procedure in a large cohort of elderly patients reported to the EBMT.
PATIENTS AND METHODS: All consecutive autoHCT in recipients 65 yo and older reported to the EBMT between 2000 and 2014 were included. Data collection and outcome analysis followed EBMT registry and statistical guidelines.
RESULTS: A total of 21390 autoHCT, including 3514 second or subsequent procedures, from 515 EBMT centres in 45 countries were identified: the median age was 67 (65-89), 17531 were 65-69 yo (Group I) and 3859 were 70 yo and older (Group II); 61% were male; 62% had MM, 30.5% LPD, 3.4% acute leukemia and 3.3% other indications; 99% of cases in both age groups used peripheral blood stem cells, and 10.3% of cases received reduced-dose preparative regimens for advanced age. Median time from diagnosis to autoHCT was 8.9 months (IQR 5.9-18.7), significantly longer for group II (9.4 vs 8.8 months; p <0.001).
AutoHCT activity in elderly patients increased over the study period from 443 out of 13163 in 2000 (3.4%) to 2444 out of 23883 in 2014 (9.8%; p<0.001). Neutrophil and platelet engraftment were achieved after a median day +12 (IQR 10-13) and +17 (IQR 14-22), respectively, and 1.4% of the cases experienced primary or secondary graft failure. The main early complication after autoHCT was mucositis (67.5%). Venooclusive disease was diagnosed in 0.8% of cases. The incidence of transplant complications did not differ between age groups. Median follow up time for survivors was 15.3 months (IQR 4.2-41.7), significantly longer for group I than for group II (15.9 vs 13.3; p<0.001). Non-relapse mortality (NRM) was 4.9% [95%CI 4.6-5.2] at 1 year and 8.3% [95%CI 7.8-8.7] at 3 years, significantly higher for Group II both at 1 year (4.6% [95%CI 4.3-5] vs 5.9% [95%CI 5.1-6.8]) and 3 years (7.8% [95%CI 7.4-8.3] vs 10.4% [95%CI 9.2-11.6], p<0.001) after autoHCT (Figure 1). Relapse incidence was 21.6% [95%CI 21-22] at 1 year and 50% [95%CI 50-51.8] at 3 years, significantly higher for group II both at 1 year (20.6% [95%CI 19.9-21.3] vs 26.6% [95%CI 25-28.2]) and 3 years (50% [95%CI 49-51] vs 55% [95%CI 53-57], p<0.001) after autoHCT. Causes of death included relapse or disease progression (76%), transplant related mortality (9.4%), secondary malignancies (4.2%) and others (10.3%). Overall survival (OS) was 87% [95%CI 86.5-87.5] at 1year and 66.7% [95%CI 66.8-68.5] at 3 years, significantly lower for Group II both at 1 year (87.7% [95%CI 87.2-88.3] vs 83.4% [95%CI 82-84.7]) and 3 years (69.1% [95%CI 68.2-70] vs 60.8% [95%CI 58.8-62.9], p<0.001) after autoHCT. Multivariate analysis showed that increased age (in 5-year intervals), diagnoses other than MM, and time from diagnosis to autoHCT >12 months all had an independent negative impact on NRM and OS (Table 1). In addition, more recent year of transplantation had an additional independent favorable impact on OS.
CONCLUSIONS: Our results confirm the feasibility of autoHCT in a large-series of elderly patients, with acceptable NRM and OS at 1 and 3 years overall, despite the significant poorer outcomes in those 70 yo and older. In addition, this study identifies in multivariate analysis factors that have an independent impact on NRM and OS of elderly patients undergoing autoHCT. With the limitations of a retrospective registry analysis, this is presumably a highly selected fraction of patients aged 65 and older considered for autoHCT. Nevertheless, our data in a large cohort of such patients convincingly suggest that age per se should not be an exclusion criteria to consider autoHCT in this population. Thus, they also further endorse the need to assess comorbidity and frailty beyond age in older autoHCT candidates to improve outcomes further. Studies to assess the benefit from autoHCT in elderly patients with particular diseases and indications are warranted.

Disclosures
Montoto: Roche: Honoraria; Gilead: Research Funding. Dreger:Novartis: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Roche: Consultancy. Goldschmidt:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Garderet:BMS: Consultancy, Honoraria; Amgen: Consultancy; Takeda: Consultancy; Novartis: Consultancy.