Outcome of Patients Aged ≥60 After Allogeneic Hematopoietec Cell Transplantation: Age Has No Impact on Survival
Authors: Federmann Birgit , Faul Christoph , Vogel Wichard , Kanz Lothar , Bethge Wolfgang A. 
Published: October 2019

Abstract
Abstract 3540
Historically, allogeneic hematopoietic cell transplantation (HCT) has been offered only to patients with good performance status and below the age of 60. However, the peak incidence of most hematologic malignancies is above 60 years of age. The introduction of reduced intensity conditioning (RIC) regimens enabled successful allogeneic HCT in patients with considerable comorbidities and older than 60 years. The impact of age on outcome of allogeneic HCT in patients ≥60 years has not been evaluated extensively. We retrospectively analyzed 109 consecutive patients (f=43, m=66) aged≥60 who received allogeneic HCT 2000–2010 at our institution. Median age of the patients was 65 years (range, 60–76). Patients were grouped in two cohorts depending on age: group 1 aged 60–65 years (n=60, median age=63) and group 2 aged 66–76 years (n=49, median age=68). Diagnoses were acute leukemia (AML n=65, ALL n=1), myelodysplastic syndrome (n=14), osteomyelofibrosis (n=7), non-Hodgkin lymphoma (n=9), multiple myeloma (n=8), aplastic anemia (n=1), chronic myeloid leukemia (n=2) and chronic lymphatic leukemia (n=2). At time of HCT, 41 of the patients were in complete remission (CR), 68 in partial remission (PR) (group 1: CR 21, PR 39; group 2: CR 20, PR 29) and 18 patients had a preceding HCT, 14 in group 1. Conditioning regimens were grouped in high (TBI/Bu+Cy, n=5, all group 1), intermediate (FLAMSA, Flu/Mel/BCNU, n=28, group 1=11, group 2=17), low (FLU+alkylans, n=48, group 1=32, group 2=16) and minimal (2GyTBI/Flu, n=28, group 1=12, group 2=16) intensity. Intermediate intensity conditioning was particularly used for high risk patients in PR (25/28). 22 patients were transplanted from matched related (MRD), 46 from matched unrelated (MUD) and 41 from mismatched unrelated donors (MMUD). Kaplan-Meier-estimated 3-year overall survival (OS) was 45% for all patients, 32% for group 1 and 62%, for group 2, respectively (p=0.02), with more patients with high risk constellation in group 1. 3-year OS for patients transplanted with MUD was 57%, with MMUD 46% vs. with MRD 0% (p=0.01). Non-relapse-mortality was 28% for all patients, 40% in group 1 and 12% in group 2, probably due to the higher intensity in conditioning in group 1. The outcomes with intermediate, low and minimal intensity conditioning were comparable, while all patients after high intensity conditioning died. Table 1 describes Kaplan-Meier estimated 3-year-OS and statistical univariate analysis by log-rank test in the different subgroups.
Table 1. 3-year OS (in%) All Group 1 Age 60–65 Group 2 Age 66–76 Remission CR 52 p=0.25 31 p=0.76 77 p=0.15 PR 40 32 50 Conditioning high 0 p=0.5 0 p=0.08 – p=0.38 intermediate 52 50 53 low 48 43 57 minimal 45 17 67 Donor MRD 0 p=0.01 0 p=0.06 73 p=0.45 MUD 57 53 65 MMUD 46 40 33 GVHD acute no 18 p=0.003 13 p=0.008 33 p=0.27 ≥II 43 53 58 chronic no 39 p=0.25 36 p=0.70 52 p=0.08 limited 52 30 100 extensive 50 30 67
In group 1 the outcome of minimal conditioning was inferior compared to intermediate and low conditioning while patients in group 2 had a better outcome with minimal vs. low and intermediate conditioning. Incidences of acute GVHD ≥II, limited and extensive chronic GVHD (cGVHD) were 10%, 28% and 13%, respectively. In group 1, acute GVHD ≥II occurred in 13% and cGVHD in 35%, in group 2 in 5% and 41% of the patients, respectively. Acute GVHD ≥II was associated with inferior outcome (3-year OS of 18% vs. 43%, p=0.003) while cGVHD had a positive impact on OS. In group 2 patients with limited cGVHD showed better 3-year OS than patients without cGVHD (67% vs. 52%, p=0.12). Age alone had no major impact on outcome of allogeneic HCT. Patients aged ≥60 seemed to benefit from the use of MUD rather than an older MRD. Chronic GVHD had a positive influence on survival. Our data indicate that the regimen used should be tailored to disease risk and patient performance status.

Disclosures:
No relevant conflicts of interest to declare.