Transplantation Related Toxicity and Mortality in Older Autologous Hematopoietic Cell Transplantation Recipients
Authors: Belete Hewan , Burns Linda J. , Shanley Ryan , Nayar Manju , McClune Brian , Sahni Nishant , Lazaryan Aleksandr , Bachanova Veronika , Weisdorf Daniel J. , Arora Mukta 
Published: October 2019

Abstract
High dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is the standard of care for patients with relapsed aggressive Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and after initial treatment of multiple myeloma (MM). With advances in supportive care, AHCT is increasingly being performed for patients older than 60 years of age. However, prior studies evaluating outcomes of transplant in older AHCT recipients are inconsistent, with conflicting data on risk of complications and major outcomes of non-relapse mortality (NRM), overall survival (OS) and progression free survival (PFS). Data from registry studies report lower NRM in young and old patients, in recent years, likely due to improvement in supportive care. We analyzed patients receiving an AHCT for MM or lymphoma in a contemporary cohort (2010-2012) receiving consistent treatment and supportive care. We hypothesized that with improved supportive care, there would be little or no difference in outcomes of younger (40-59 years) versus older (> 60 years) AHCT recipients, examining engraftment, OS, PFS, NRM and non-hematologic grade 3-5 toxicities within one year post AHCT.
Study cohort and Methods: All patients > 40 years (n=144) who underwent an AHCT for lymphoma (NHL, n = 56; HL, n = 11) or MM (n = 77) from 2010 -2012 at University of Minnesota were included. Engraftment, OS, PFS, NRM and non-hematologic grade 3-5 toxicities within the first year post AHCT were compared between the two cohorts (age 40-59 years, > 60 years).
Results. The median age at transplant was 54 years (range 40-59 years) in the younger cohort (n= 77) and 65 years (range 60-76 years) in the older cohort (n=67). Older recipients more often had MM and were less often in complete remission. Over 95% of patients in both groups had a Karnofsky performance status (KPS) of > 80% (p=0.46) while 27% in the older group versus 22% in the younger group had a HCT-CI comorbidity score of > 3 (p= 0.72). We examined 17 categories of non-hematologic grade 3-5 toxicities. The frequency of infections during neutropenia was significantly higher in the older group (64% vs. 44%; 0=0.02). The proportion of patients with any grade 3-5 toxicity was also higher in the older group (84% vs. 67%, p= 0.03). In multivariate analysis, after adjustment for gender and disease, older age (> 60) was significantly associated with higher odds ratio (OR: 2.57, 95% CI: [1.09-6.05]) of grade 3-5 toxicity (Table 1). Based on the high-risk variables shown in Table 1, the predicted probability of grade 3-5 toxicities within one year (adjusted for age, gender and disease) was highest (94%) in females > 60 years with NHL and lowest in males age 40-59 years with HL (47%). There was no difference in time to neutrophil and platelet engraftment (Table 2). Two older recipients (cumulative incidence of NRM: 3%) and no younger recipients had NRM within one year. After a median follow up of two years, the probability of OS at two years was lower in the older group (76% vs. 90%, P=0.04) but no difference was noted in disease relapse or PFS.
Conclusion: AHCT can be performed safely in older recipients. However, the higher toxicity and slightly higher NRM in this population needs attention. Studies focusing on risk-stratification in older patients (including geriatric assessments) would further help predict toxicity. Further studies addressing enhanced supportive care needs for older patients who are most likely to benefit are indicated.
Table 1: Risk factors for grade 3-5 toxicities Factor OR 95% CI P Age 40-59 1.00 Age 60-76 2.57 1.09 – 6.05 .03 Male 1.00 Female 2.24 0.96 – 5.24 .06 Multiple myeloma 1.00 Hodgkin lymphoma 0.82 0.21 – 3.18 .77 Non-Hodgkin lymphoma 2.67 1.07 – 6.68 .04
Table 2: Outcomes by age Age 40-59 Age 60+ P Days to ANC recovery median (IQR) 10 (10-11) 11 (10-11) 0.15 Days to Platelet > 20K median (IQR) 19 (17-21) 18 (17-21) 0.86 1 year NRM (95% CI) 0 3 (1-7) 0.05 2 year relapse (95% CI) 47 (34-60) 39 (27-51) 0.44 2 year OS (95% CI) 90 (82-98) 76 (65-87) 0.04 2 year PFS (95% CI) 53 (41-65) 55 (43-67) 0.80

Disclosures
Bachanova: Seattle Genetics, Inc.: Consultancy, Research Funding.