Comparison of Outcomes in Elderly Patients with Non-Hodgkins Lymphoma Undergoing High-Dose Chemotherapy to Their Younger Counterparts: Greater Morbidity but No Significant Impact on Overall Survival.
Authors: Wildes Tanya M. , Augustin Kristan M. , Vij Ravi , Bartlett Nancy , DiPersio John F. , Devine Steven M. 
Published: October 2019

Abstract
The incidence of Non-Hodgkins lymphoma (NHL) increases with age. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a widely applied treatment for advanced NHL. Patients 60 years of age or above are at higher risk for recurrent disease but few studies have addressed the tolerability and outcomes of ASCT in comparison to younger patients conditioned and treated in a homogeneous manner. With this in mind, we compared outcomes of 153 consecutive patients (pts) with NHL who underwent high-dose chemotherapy at our institution between January 1, 2000 and August 31, 2004, focusing on the influence of age at the time of transplant.. All 153 pts received the identical BEAM conditioning regimen followed by ASCT. Ninety four pts were under the age of sixty (median age 51, range 21–59) and 59 were aged 60 or older (median age 64, range 60–74). Supportive care was the same in both groups. We compared data on stem cell mobilization, engraftment, toxicities of conditioning, post transplant morbidity, relapse, and mortality between the older and younger individuals. There were no significant differences in the CD34+ cell doses collected, transplanted, or number of leukapheresis attempts required to achieve an adequate CD34+ cell dose. Older patients experienced significantly more grade 3 mucositis (40% vs 18%) and had higher risks of gram negative bacteremia (20% vs 13%) and candidemia (10% vs 4%) than the <60 group. However, days to transplant discharge, days of neutropenic fever, and days on iv antibiotics were similar. Treatment related mortality was somewhat higher in the ≥ 60 group (8.4% vs 5.3%), but this was not statistically significant (p=0.65). Neutrophil engraftment was similar between both groups but recovery to platelets >20,000/ul (21.5 vs 16 days) and 50,000/ul (33 days vs 23 days) was significantly longer in the older patients despite transplantation of similar CD34 doses (p<0.01 for both comparisons). Both groups were well balanced for proportion of patients with high grade and low grade NHL as well as those in complete or partial remission at the time of transplant. Relapse rates at 2 years did not differ significantly between the two groups (36% in > 60 vs 27% in ≥ 60; p=0.28). With a median of 22 months follow-up, the Kaplan-Meier estimate of two year progression free survival was 74 +/− 5% in the younger group and 61+/− 7% in the older group (p=0.76). In summary, older individuals conditioned with BEAM chemotherapy experience more severe mucosal toxicity than younger patients, which may predispose to higher risk for bacteremia and fungemia. Platelet recovery appears to be prolonged in older individuals, possibly as a result of qualitative stem cell defects or increased mucosal damage. Despite these differences, progression free survival is similar in patients over the age of 60 in comparison to younger individuals. Future efforts should focus on reduction of mucosal toxicity and infectious complications in older patients in order to further reduce morbidity and improve overall outcomes.