Prospective Phase II Study of Biologic Assignment One Vs Two Unit Umbilical Cord Blood Transplant (UCBT) in the Reduced-Intensity Conditioning Setting

• Published in: Blood 2008-11, Vol.112 (11), p.1960-1960
• Main Authors: Kindwall-Keller, Tamila L., Hegerfeldt, Yael, Fu, Pingfu, Lazarus, Hillard M., Cooper, Brenda W., Barr, Paul, Gerson, Stanton L., Meyerson, Howard, Erinc, Sally, Creger, Richard J., Fanning, Laura, Greco, Nicholas, Haviernik, Peter, Lesniewski, Mathew, Laughlin, Mary J.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.1960.1960

Retrospective analyses of UCBT using early historic controls show more robust graft vs leukemia effect in recipients given two-units vs one-unit. We present herein analyses from this single institution, prospective phase II clinical trial conducted 9/2003 to 5/2008 comparing 1 vs 2 unit UCBT in patients (pts) with high-risk, recurrent hematologic malignancies treated with reduced-intensity conditioning. The number of units infused in each pt was determined by biologic assignment based on the number of cells contained in the primary unit. Pts received 1 UCB unit if the cell dose was ≥ 2.5 x 107 nucleated cells/kg recipient weight and 2 UCB units for a minimum total combined cell dose of 1.5 x 107 cells/kg recipient weight if only smaller units were available. The UCB grafts were matched at ≥ 4/6 HLA loci (antigen level matching at class I A and B loci, and allele level matching class II DRB1 loci) except for 1 pt (3/6). If 2 UCB units were used they needed to be at least a 4/6 match to each other. The conditioning regimen included: Fludarabine 35 mg/m2/d x 5 days, cyclophosphamide 1 g/m2/day x 2 days, ATG 30 mg/kg/day x 2 days and single fraction TBI 200 cGy. Thirty-seven pts, 14 females, 23 males, median age 49 (range 20–71) years were enrolled. Most pts had advanced stage or high-risk hematologic malignancies; 28 pts (76%) had MDS/AML and 9 (24%) had other hematologic malignancies. Two pts underwent 2 transplants on this study after relapsing following the first UCBT. Twenty-seven pts received 1 unit and 10 pts received 2 units. The median follow up for survivors is 17.9 (range 1.2–55.9) months (mos) and median follow up for all pts is 10.1 mos. Median time to an ANC > 500/μL on 3 consecutive evaluations was 24.5 (range 12–55) days and 25 (range 13–43) days for 1 and 2 units, respectively (p=0.361). Median time to platelets > 20,000/μL without transfusion support on 3 consecutive evaluations was 38.5 (range 24–84) days and 63.5 (range 38–117) days for 1 and 2 UCB units, respectively (p=0.009). Median event-free survival (EFS) and median overall survival (OS) did not differ comparing 1 vs 2 units: 127 (range 16–1785+) days and 216 (range 16–1785+) days for 1 unit UCBT vs 92.5 (range 27– 1545+) days and 112 (range 27–1545+) days for 2 unit UCBT. The Kaplan-Meier (K-M) OS for 1 unit UCBT was 35.6% at 4 years compared to 33.3% for 2 unit UCBT (p=0.403). No statistically significant difference in K-M 4 year EFS was seen (p=0.894). At day +100, 7 pts (26%) had