Comparative Single-Institute Analysis of Cord Blood Transplantation From Unrelated Donors with Related Bone Marrow or Peripheral Blood Stem-Cell Transplants in Elderly Patients with Hematologic Diseases After Reduced Intensity-Conditioning Regimen.
Authors: Uchida Naoyuki , Nishida Aya , Shimazu Hiroshi , Nakano Nobuaki , Ishiwata Kazuya , Tsuji Masanori , Yamamoto Hisashi , Asano-Mori Yuki , Masuoka Kazuhiro , Wake Atsushi , Yoneyama Akiko , Makino Shigeyoshi , Taniguchi Shuichi 
Published: October 2019

Abstract
Abstract 2295
Poster Board II-272

Introduction:
Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning has been widely applied to those who have advanced hematologic diseases and are not eligible for conventional conditioning. Although bone marrow or peripheral blood from related donors (rBM/PB) have been the first choice of graft when available, followed by unrelated adult donor or cord blood (CB), true superiority of rBM/PB over others can still be controversial. Elderly patients have difficulty finding related donors since their siblings are also in their elderly who have higher chance of having co-morbidity relative to younger patients. Rapid availability is the advantage of rBM/PB and CB share over unrelated adult donor, which enabled adapting similar policy of performing transplant possible, especially for elderly patients, given the significantly higher treatment-related mortality for elderly.

Design and Methods:
We retrospectively reviewed patients aged 55 and older who underwent reduced intensity allogeneic stem-cell transplantation using CB or rBM/PB at our institute from Jan. 2004 to Dec. 2008 consecutively. Patients who were considered for allogeneic transplant and had available 6/6 or 5/6 HLA-matched relatives performed rBM/PB transplants, whereas those who lacked rBM/PB donors underwent CB transplants. Patients who had prior history of transplantation, were in poor performance status (ECOG PS 2 and greater), had active bacterial or fungal infections at the time of conditioning, had diagnosed as multiple myeloma, adult T-cell leukemia, non-malignant diseases were excluded.

Results:
Two-hundred and thirty-two (171 CB and 60 rBM/PB) RI transplantation were performed from Jan. 2004 to Dec. 2008 at our institute, and 82 (61 CB and 21 rBM/PB) were eventually subjected to the analysis after excluding those who were ineligible according to the above mentioned criteria. The diagnoses included were AML (n=51), MDS (n=9), ALL (n=9) CML/MPD (n=4), and ML (n=9). Fifty-eight (71%) had high risk diseases, and 24 (29%) were in ECOG PS 2. Recipients of CB and rBM/PB were comparable in terms of diagnosis, disease risk (standard vs high), ECOG PS (0-1 vs 2), and year of transplant (2004-2005 vs 2006-2008). The median age for rBM/PB recipients was slightly younger (median 60, range 55-66) than that for CB (median 62, range 55-69, P < .03). CB recipients received more serologically HLA-mismatched grafts (98% vs. 3%, P<.0001), had shorter duration of donor search (median 43 days vs. 148 days, P<.0001), were conditioned more frequently with fludarabine/melphalan/TBI regimen (70% vs. 5%, P<.0001), used more tacrolimus (100% vs. 29%) and less methotrexate (0% vs. 100%, P<.0001) for GVHD prophylaxis, compared to rBM/PB recipients. Median follow-up time of survivors were 766 (25-1769) days for CB and 824 (173-1345) for rBM/PB recipients respectively. CB recipients showed slower neutrophil recovery (median 21 (12-43) days vs. 15 (11-21) days), and lower rate of myeloid engratment (75% vs. 100%, P<.01). The overall (OS) and event-free survival (EFS) at 2 years post-transplant showed no statistically significant differences between CB (OS 29+/-6% and EFS 23+/-6%) and rBM/PB recipients (OS 37+/-12% and EFS 29+/-11%). 23/43 (47%) CB recipients' death was due to non-relapse causes, whereas 9/12 (75%) rBM/PB recipients' death was due to relapse. Cumulative incidences of relapse at 2 years were 44+/-0.5% for CB and 49+/-1.4% for rBM/PB recipients (N.S.).

Conclusions:
These data suggest that, for elderly patients, comparable results can be expected using CB, which opens more opportunity for elderly patients to undergo allogeneic transplants who generally have difficulty finding healthy related donors compared to younger patients. However, before CB become the first choice of graft, higher rate of engraftment failure and non-relapse mortality, particularly during early period post-transplant, need to be overcome, and, at this moment, rBM/PB is still the optimal graft of choice when available over CB.

Disclosures:
No relevant conflicts of interest to declare.