Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) for Elderly Patients with Hematological Malignancies
Authors: Nakae Yoshiki , Kojima Rie , Chizuka Aki , Osajima Yuko , Noguchi Toshiyuki , Miyamoto Kou , Oota Masatsugu , Miyakoshi Shigesaburo 
Published: October 2019

Abstract
Abstract 2349

Introduction:
Incidence of hematological malignancies is higher in elderly population. However, standard chemotherapy has not been established and the potential role of RICBT has remained unclear. This study reports the results of RICBT for elderly patients with hematological malignancies, retrospectively.

Objective:
To investigate the feasibility of RICBT. Primary endpoints were engraftment and overall survival (OS). secondary endpoint was transplant-related mortality (TRM).

Patients and Methods:
Between Feb.2009 and Jun.2010, 29 patients (median age 70 years, range 58–76) received RICBT for hematological malignancies. Primary diseases were divided into 2 groups; advanced (intermediate and high risk; n=21) or standard (n=8). All cases in 70's were included in the high risk. Median follow up time was 238 days (range 8–464).Conditioning regimen and GVHD prophylaxis consisted of fludarabine, busulfan or cyclophosphamide, and TBI 2Gy with tacrolimus± MTX for <70 years(n=18), fludarabine, busulfan or cyclophospamide, and ATG 7.5mg/kg with cyclosporine ± MTX for >70 years (n=11) and <70 years with comorbidities. Median total transplanted nucleated cells: 3.2 × 10|jE7 cells (2.0–4.8); Median CD34+: 0.4× 10|jE5 cells (0.3–2.9); HLA match: 5/6 (n=1), 4/6 (n=28). Time to event curves were plotted by using the actuarial method of Kaplan-Meier, and differences between curves were analyzed by log-rank tests.

Results:
Neutrophile (>500/μL) and platelet engraftment (>20,000/μL) were observed in 89.6% (95% CI; 79–100) at day 60 (median; 18.0 days, range; 13–28), and 62.1% at day 100 (median; 36.5 days, range; 17–60), respectively. Neutrophile engraftment was 100% in TBI regimen (median; 18 days, range; 13–28), 75% in ATG regimen (95% CI; 51–100, median; 19 days, range; 16–27)(p=0.04). Platelet engraftment was 77% in TBI regimen, 42% in ATG regimen, respectively (p=0.06). Primary graft failure occurred in 3% of all cases. Cumulative incidence of acute GVHD (II-IV) was 58% (95% CI; 39–78) at day 100 (median; 27.5 days, range; 13–82), 81% (95% CI; 62–100, median; 28 days, range; 17–82) in TBI regimen and 12.5% (95% CI; 0–35, median; 13 days, range; 13) in ATG regimen, respectively (p=0.01). The 1-year estimated OS was 51% (95% CI: 25–77) in all cases, 51% (95% CI: 13–90) in TBI, and 48% (95% CI: 18–77) in ATG, respectively (p=0.08). According to the age, OS was 80% (95% CI: 45–80) in 50's, 53% (95% CI: 20–86) in 60's, and 38% (95% CI: 0–77) in 70's (P=0.0765). Causes of TRM included infections (n=5 including 3 cases in 70's), TMA (n=2). Incidence of TRM at day 100 was 20% (95% CI; 4–35, median; 47 days, range; 8–79), 7% in TBI regimen (95% CI; 0–21, median; 79days), 41% in ATG regimen (95% CI; 9–72, median; 30 days, range; 9–72). Incidence of TRM, according to the age, was 40%,0%, and 52% in 50's,60's, 70's, respectively.

Discussion and Conclusion:
Because of the high incidence of high risk disease and TRM, despite low incidence of GVHD, RICBT is associated with a low OS in patients over 70 years compared with those who are under 70 years. Eligibility of RICBT needs to be investigated, especially in 70's patients, and further studies are warranted to clarify the safety in elderly patients.

Disclosures:
No relevant conflicts of interest to declare.