Reduced Intensity or Non-Ablative Hematopoietic Cell Transplantation in Older Patients with Non-Hodgkin Lymphoma (NHL): Encouraging Survival for Patients ≥55 Years
Authors: McClune Brian , Pedersen Tanya L. , Ahn Kwang W , Warlick Erica D , Pidala Joseph , Waller Edmund K , Rizzo J. Douglas , Cairo Mitchell S. , Woolfrey Ann , Artz Andrew , Lazarus Hillard M. , Weisdorf Daniel J. 
Published: October 2019

Abstract
Abstract 1015
Non-Hodgkin lymphomas (NHL) disproportionately affect older patients. Hematopoietic cell transplantation (HCT) with non-ablative conditioning regimens is increasingly used to treat this population. We analyzed data reported to the CIBMTR on 1248 patients receiving either non-myeloablative (NMA) or reduced-intensity conditioning (RIC) HCT from 2001–2007 for both aggressive (n=668) and indolent (n=580) NHL testing the association of age on transplant-related mortality (TRM), relapse, engraftment, acute and chronic graft-versus-host disease (GVHD), progression-free (PFS) and overall survival (OS). Patients were stratified into 3 age cohorts: 40–54, 55–64, and ≥65 years. Clinical characteristics were mostly well-matched across age cohorts, but more frequent aggressive NHL histologies occurred in the oldest age group [67% vs. 49% (age 40–54) and 57% (age 55–64); p=0.0008] and fewer patients ≥65 years had prior autografts (9% vs. 26% and 24% in the younger groups; p=0.002); 30% of those ≥65 had resistant disease at HCT (vs. 25% and 23% in younger cohorts; p=0.79). Univariate analysis demonstrated no statistically significant differences in the incidence of relapse, acute or chronic GVHD across age cohorts (Table 1). We observed lower 1 year TRM for the youngest group, but TRM was similar in the two older cohorts. PFS and OS were also inferior in the two older cohorts, but no differences between those aged 55–64 and ≥65 were noted. Multivariate analysis (Table 2) revealed no independently significant impact of age on the incidence of acute (p=0.91) or chronic GVHD (p=0.66), or on relapse (p=0.06). Older age ≥55 years, lower Karnofsky performance status (KPS), and human leukocyte antigen (HLA) match disparity adversely impacted TRM, PFS, and OS. Advanced disease status (CR1/2 vs. PR1/2, or resistant) at HCT also significantly worsened TRM, relapse (p<0.0001), PFS and OS. Histology (aggressive vs. indolent) did not impact any multivariate model of outcomes. Compared to NMA regimens RIC worsened acute (p=0.007) and chronic (p=0.002) GVHD and OS (p=0.03), but not TRM or PFS. We conclude that patients ≥55 receiving non-ablative HCT for NHL have only modestly worse outcomes with no further decrement in those ≥65 years. These results are, however, influenced by KPS and disease status at time of HCT, and by HLA donor/recipient mismatch. Despite higher risk characteristics, 3 year survival still approached 40% for even the oldest groups making HCT a worthwhile option for these patients. Future work should focus on refining techniques for patient selection and optimizing conditioning regimens to improve these already encouraging results.Table 1.Univariate probabilities of patients receiving HCT for NHLN40–54N55–64N≥ 65P61455282TRM, 1 year22 (19–26)%27 (23–31)%34 (24–44)%0.05Relapse, 3 years28 (24–32)%33 (29–37)%33 (23–44)%0.22PFS, 3 years44 (39–48)%32 (28–36)%27 (17–37)%<0.0001OS, 3 years54 (50–58)%40 (36–44)%39 (28–50)%<0.0001Follow-up, median (months)56 (3–111)47 (2–111)47 (2–96)Table 2.Factors affecting multivariate analysis in patients receiving HCT for NHLAgeTRMPFSOSHRPHRPHRP    40–541.01.01.0    55–641.52<0.00011.37<0.00011.47<0.0001    65+1.570.021.330.041.470.01KPS    ≥ 801.01.01.0    < 801.87<0.00011.63<0.00011.87<0.0001HLA match    Identical sib1.01.01.0    URD well matched1.36<0.011.130.151.300.004    URD partial match2.30<0.00011.390.0031.90<0.0001    URD mismatch2.9<0.00012.28<0.00012.210.0001Disease Status    CR1/CR21.01.01.0    PR1/PR21.270.061.45<0.00011.290.01    Resistant1.90<0.00012.28<0.00011.97<0.0001

Disclosures:
No relevant conflicts of interest to declare.