Hematopoietic Stem-Cell Transplantation from Unrelated Donors in Elderly Patients (&gt; 55 Years): Older Age Is No Longer a Contraindication When Using Reduced Intensity Conditioning.
Authors: Shimoni Avichai , Kröger Nicolaus , Zabelina Tatjana , Ayuk Frances , Hardan Izhar , Yeshurun Moshe , Shem-Tov Noga , Avigdor Abraham , Ben-Bassat Isacc , Zander Axel , Nagler Arnon 
Published: April 2020

Abstract
Allogeneic stem-cell transplantation (SCT) is a potentially curative approach for patients (pts) with hematologic malignancies. However, it is associated with a high risk of treatment-related complications. Risks are significantly increased with advanced age, concurrent medical problems and with unrelated donors, therefore most centers limit unrelated-donor SCT to pts younger than 50–55 years. Moreover, hematological malignancies are more common and have a worse prognosis in the elderly, thus many pts who could benefit from SCT were often deferred from this potentially curative approach. Reduced-intensity conditioning allowed extension of allogeneic SCT to a wider pt population including the elderly, however there is only limited data on the feasibility and outcome of unrelated-donor SCT in elderly pts over age 55 years. In this study we report our experience with 40 pts over age 55 having unrelated-donor SCT following reduced-intensity conditioning. The median age was 58 years (range, 55–66). Eleven pts were over age 60 years. Diagnoses included AML (n=19; 7 CR1, 9 CR2, 3 refractory; 12 secondary to MDS or prior chemotherapy), MDS (n=4), myelofibrosis (n=2), CML (n=3), multiple myloma (n=8), non-Hodgkin’s lymphoma (n=4). The preparative regimen consisted of fludarabine combined with oral busulfan (8 mg/kg, n=8), intravenous busulfan (busulfex, 6.4 mg/kg, n=15), treosulfan (30 g/m2, n=5) or melphalan (100–150 mg/m2, n=12) and serotherapy, either ATG (n=36) or alemtuzumab (n=4). Thirty-six pts engrafted with a median of 14 days. Four pts died prior to engraftment. With a median follow-up of 14 months (range, 1– 54), 21 pts are alive and 19 have died, 13 of treatment-related causes and 6 of relapse. The probabilities of overall and disease-free survival at 1-year after SCT were 46% (95 CI, 28–63%) and 40% (95 CI, 23–57%), respectively. The cumulative incidence of non-relapse mortality (NRM) and relapse at 1 year were 35% and 25%, respectively. Acute GVHD grade II–IV and chronic GVHD occurred in 36% and 45%, respectively. The status of disease at SCT and the conditioning regimen used were the most significant predictors of outcome. Pts with chemosensitive or untreated malignancy had an OS of 52% whereas pts with refractory malignancy had an OS of 16% (p=0.05). Pts conditioned with fludarabine and busulfex or treosulfan had an OS of 57% compared with 35% in pts conditioned with fludarabine and melphalan or oral busulfan due to increased NRM with the later regimens (p=0.04). Multivariable analysis confirmed the independent impact of these factors with hazard ratios for decreases OS of 3.1 and 3.2, respectively. When a more homogenous subgroup of 23 pts with AML or MDS was analyzed, the 1-yaer OS and DFS were 49% (95 C.I. 24–75%) and 43% (95 C.I. 18–68%), respectively. NRM was 24% (95 C.I. 11–54%). In conclusion, unrelated-donor SCT is feasible in elderly pts, with outcomes that are similar to younger pts. Favorable outcome was observed in pts with myeloid malignancies, and those transplanted in remission and early in the course of disease. The newer regimens containing intravenous busulfan or treosulfan were less toxic translating into better outcome. Age alone should no longer be considered a contraindication to unrelated-donor SCT.