Safety and Efficacy of Autologous Hematopoietic Cell Transplantation for Elderly Patients with Lymphoma: Chemosensitive Disease Rather Than Age or Co-Morbidity Index Predicts Outcome

Abstract

Introduction: High dose chemotherapy (HDT) and autologous hematopoietic cell transplantation (AHCT) are considered standard of care as first line therapy in mantle cell lymphoma (Dreyling et al., 2005; Geisler et al., 2012) and in first line refractory and chemosensitive relapse Non-Hodgkin Lymphoma (NHL) (Philip et al., 1995) . The development of hematopoietic cell transplant comorbidity index (HCT-CI) (Sorror et al., 2009) for recipient selection and transplant risk evaluation have impacted on patient selection. Over the last decade, most transplant program have seen an increase in the median age of AHCT recipients(McCarthy et al., 2013). Limited data are available to optimise elderly patients selection for transplantation while minimising the risk of treatment related toxicity and mortality (TRM). The goal of this study was to identify factors impacting the safety and efficacy of AHCT in the elderly NHL patients in order to better select those who will benefit from this intervention. Method: This is a single center, retrospective study examining outcomes of AHCT in elderly patients (≥60 years old) with NHL. Between January 1st, 2008 and January 1st, 2015, 90 patients met the inclusion criteria and were included in the study. Patients signed an informed consent and the ethics committee of our institution approved the study. Progression-free-survival (PFS) and overall survival (OS) were analyzed according to age at time of transplantation, HCT-CI, lymphoma histology and disease status at time of transplant. Toxicities were analyzed according to age and HCT-CI. Results: Median age at time of NHL diagnostic was 60 years (range 42 to 68) and 63 years at time of transplant (range 60 to 69). One third (33%) of our cohort was ≥65 years old. Histologic sub-type was mainly composed of follicular (36%), mantle cell (20%) and large B-cell lymphoma (38%). 50% of patients had high-risk disease and 31% had low risk disease. HCT-CI was low-risk in 34%, intermediate risk in 40% and high-risk disease in 26%. BEAM/BEAC conditioning regimen was used in 94%. The median graft CD34+/kg cell dose infused was 4.87. The median time to neutrophil engraftment was 10 days (range 8 to 14 days) and platelet recovery was 16 days (range 11 to 43 days). The incidence of febrile neutropenia was 92% with 2% admission to the intensive care unit (ICU) with no difference between patients younger or ≥65 years old. Our cohort received a median of 8 days of antibiotics (range 0 to 41 days). Absolute lymphocyte count < 0,3 X 103 cells/uL at 14 days after transplant was associated with higher incidence of septic choc (p=0,024) and ICU admission (p=0,034). Age ≥65 year was not associated with an increase TRM and was surprisingly associated with less total parenteral nutrition (p=0,046) and narcotics uses (P=0,011). The median length of stay was 26 days. The median follow-up was 27 months (range, 1 to 87), median PFS of 46 months (Confidence Interval (CI); 95%, 24,4-67,6) (graph 1) and OS not reached (graph 2). The estimated 5 years OS is 62% and PFS is 40%. Transplant related mortality (TRM) was only 1% at 100 days and 2% at 1year after transplant. The only 2 patients who died from TRM died from cardiac arrest (1 month) and from an unknown cause (3 months). The 1-year progression rate was 30% (graph 3) and mortality rate only 12%. Progressive disease status following first line therapy was associated with a worse PFS compared to the achievement of a complete remission (Hazard Ratio (HR) 2,77; CI 95%, 1,18; 6,49). Progressive disease status at time of transplant was also associated with a lower PFS (HR 9,30: CI 95% 2,55 to 33,92) and OS (HR 13,44: CI 95% 2,68 to 67,48). HCT-CI score did not correlate with OS. International Prognostic Index (IPI), age and treatment type did not influence PFS or OS. Surprisingly, HCT-CI score did not correlate with toxicities, morbidity or mortality. Conclusion: In this single center retrospective study of elderly patients with NHL, AHCT was proven to be safe and effective. Progressive disease at the time of transplant was associated with worse PFS and OS. HCT-CI did not allow the categorization of patients in different prognostics group. Lymphocyte count at day 14 could identify patients at significant risk of complications. Our data suggest that age alone should not exclude patients from transplantation. However, HDT and AHCT should be reserved to chemosensitive patients and avoided in the elderly patient with progressive disease. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.