Abstract
Relapse remains a major obstacle that limits the success of hematopoietic stem cell transplantation. Therefore, we analyzed the outcome of patients with acute leukemia transplanted with myeloablative conditioning at a single institution who had a minimum follow-up of 1 year to determine if there were any unique risk factors associated with relapse after UCBT. 96 consecutive patients were evaluated, 39 were >18 years of age, 50 were male; 46 were CMV seropositive; 50 had acute lymphoblastic leukemia (11 CR1, 27 CR2, 9 CR3+, 4 relapse), and 46 had acute myeloid leukemia (11 CR1, 20 CR2, 3 CR3+, 11 relapse). Patients received two different conditioning regimens. Regimen A consisted of cyclophosphamide 120 mg/kg, TBI 1320–1375 cGy, and ATG, followed by cyclosporine A (CSA)/methylprednisolone immunosuppression (n=53). Regimen B consisted of cyclophosphamide 120 mg/kg, fludarabine 75 mg/m2, TBI 1320–1375 cGy pre-transplant and CSA/mycophenolate mofetil immunosuppression (n=43). Patients received either one (n=67) or two (n=29) 4–6/6 HLA-matched UCB units, so that the total MNC count was >2.5 x 107/kg. Accordingly, the demographics for recipients of one or two UCB units were similar except for older age (median age 24 yrs. [range 13–42] vs. 8 yrs. [range 1–52 yrs], p<0.01) and greater weight (median wt. 70 kg [range 48–120 kg] vs. 32 kg [range 10–108 kg], p<0.01) for recipients of two UCB units. Potential risk factors for relapse that were evaluated included: age, gender, recipient CMV sero-status, diagnosis, disease risk, HLA disparity, regimen (A vs. B), and TNC (or CD34+) dose of the unit responsible for sustained engraftment. Notably, in Cox regression analysis two factors were associated with lower relapse risk: disease risk (CR1/CR2 vs CR3+/REL [RR 0.32, p=0.02]) and transplantation of two UCB units (RR 0.3, p=0.03). Importantly, the diagnosis, UCB graft cell dose, and presence of acute GVHD had no demonstrable impact. All recipients of regimen A received a single UCB unit (relapse was 28% (95% CI, 15–41%)), thus interactions between regimen A and number of UCB units could not be assessed. For patients who received regimen B and were in CR1/2, there was a significantly lower risk of relapse for recipients of two UCB units compared to one unit (11% (95% CI, 0–25%) vs. 54% (95% CI, 23–85%), p<0.01). No significant difference in relapse risk could be discerned for patients with advanced disease (CR3-REL) when comparing single vs double UCBT (p=0.48). This report is the first to suggest that the use of double unit UCB grafts may be associated with a reduced risk of relapse in patients with acute leukemia. Larger studies are needed to confirm this clinical experience and to investigate the potential mechanisms by which double unit grafts could mediate protection against relapse.
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