Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) for Over 65 Year-Old Elderly Patients with Myeloid Malignancies

Incidence of myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) 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 myeloid malignancies.

To investigate the feasibility of RICBT. Primary endpoints were engraftment and overall survival (OS). 2^nd endpoints were transplant-related mortality (TRM) and relapse rate.

Between Mar.2009 and Jul.2011, 21 patients (median age 70 years, range 65–74) received RICBT for myeloid malignancies (de novo AML; n=7, MDS related; n=14). Primary diseases were divided into 2 groups; advanced (high risk; n=11) or standard (CR1 & 2; n=10). Median follow up 9.5 months (0.3–29).Conditioning regimen was fludarabine 200mg/m2, busulfan, and TBI 2Gy(n=9) or ATG 7.5mg/kg (n=12).Immunosuppresants were tacrolimus± MTX (n=13) or cyclosporine ± MTX (n=8). Median total nucleated cells (TNC): 2.6 × 10^7 cells (2.0–4.8); Median CD34+: 0.4 × 10^5 cells (0.2–2.9); HLA match: 5/6 (n=1), 4/6 (n=20). Time to event curves were plotted by using the actuarial method of Kaplan-Meier, and differences between curves were analyzed by log-rank tests.

Neutrophile (>500/μ L) and platelet recovery (>20,000/μ L) were observed in 86% (95% CI; 82–87) at day 60 (median; 17 day, range; 12–27), 62% (95% CI; 41–83) at day 100 (median; 32 day, range; 41–83), respectively. Neutrophile engraftment was 100% in TBI regimen (median; 16 days, range; 13–20), 79% in ATG regimen (median; 19 days, range; 12–27) (P=0.09).

Platelet engraftment was 86% (95% CI; 60–100) in TBI regimen, 42% (95% CI; 14–70) in ATG regimen, respectively (p=0.02). Cumulative incidence of acute GVHD (II-IV) was 33% (95% CI; 13–53) at day 100 (median; 24days, range; 10–82), 73% (95% CI; 17–82, median; 25 days, range; 17–82) in TBI regimen and 14% (95% CI; 0–33, median; 11.5 days, range; 10–13) in ATG regimen, respectively (P=0.02). The 1-year OS was 64% (95% CI; 46–86) in all cases, 71% (95% CI; 38–100) in TBI regimen, 63% (95% CI; 37–89) in ATG regimen, respectively (P=0.55,Figure1). According to the age, OS was 81% (95% CI; 57–100) in 60’s, 45% (95% CI; 14–76) in 70’s, respectively (P=0.04). Causes of TRM included infections (n=2) and late graft failure (n=1), all cases in 70’s and received ATG. Relapse rate was 19% (95% CI; 2–36) in all cases, 43% (95% CI; 6–80) in TBI regimen, and 7% (95% CI; 3–68) in ATG regimen at 500 days, respectively (P=0.06).

RICBT with ATG regimen is associated with a high TRM in over 70 year-old high risk patients. However, ATG regimen may conduct low incidence of acute GVHD and relapse rate. Eligibility of RICBT needs to be investigated, especially in over 70 patients, and further studies are warranted to clarify the safety in elderly patients.

No relevant conflicts of interest to declare.