445 High Disease-Free Survival (DFS) Supports Continued Investigation of Double-Unit Cord Blood Transplantation (DCBT) in Children with High-Risk Acute Leukemia Especially in the Setting of Single Units with Low Dose and/or a High Degree of HLA-Mismatch

Track: Poster Abstracts
Saturday, February 14, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Andromachi Scaradavou, MD , National Cord Blood Program, New York Blood Center, New York, NY
Marissa Lubin, BA , Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Patrick Hilden, PhD , Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
Farid Boulad, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Kevin J. Curran, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Rachel Kobos, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Susan E. Prockop, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Richard J. O'Reilly, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Jo-ann Tonon, BS , Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Courtney Byam, BS , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Peter G Steinherz, MD , Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY
Neerav Shukla, MD , Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY
Aisha Nasreen Hasan, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Thomas M Renaud, M.D. , Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY
Nicole Zakak, PNP , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Nancy A Kernan, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Juliet Barker, MBBS (Hons) FRACP , Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Presentation recording not available for download or distribution as requested by the presenting author.

Introduction: DCBT in children with acute leukemia is controversial given the findings of the recent BMT CTN randomized study. However, many children will not have adequate single-units based on the recent CIBMTR analysis (cryopreserved TNC > 3.0 x 107/kg and 6-8/8 allele donor-recipient HLA-match). Methods: We analyzed 35 consecutive pediatric DCBT patients (pts) treated for acute leukemia (10/2005-2/2013). All CBT recipients in this period received 2 units. Results: Median pt age was 7.5 yrs (range 0.8-18), median weight was 28 kg (range 8-75), and 69% had non-European ancestry. Seventeen pts had AML: 6 CR1 (one each with M7, secondary 5q- MDS, FLT-3 ITD, Ph+, Down syndrome MRD+, germline mutation CEBPa), 8 CR2 (one MLL MRD+), 1 CR3, and 2 in aplasia. Seventeen pts had ALL: 10 CR1 [3 Ph+ (one MRD+), 2 T-cell ALL, 1 MLL, 1 L3 disease, and 3 multiple inductions], 4 CR2, 3 CR3. One pt had advanced CML. Conditioning was Cy120/Flu/TBI1375 (N = 21, 60%) or chemotherapy-only (N = 14, 40%, 10 Clo/Mel/Thio, 4 Bu/Mel/Thio). GVHD prophylaxis was CNI/ MMF. Units had a high degree of donor-recipient HLA-allele disparity (Table). The cumulative incidence of sustained donor neutrophil engraftment was 94% (95%CI:78-98, median 21 days, range 12-33), and hematopoiesis was mediated by a single unit. Day +180 platelet engraftment ≥ 50 x 109/l was 82% (95%CI: 64-92, median 51 days, range 39-299). CD4+ count recovery was prompt: mean day 60 201 (SD:+/-180), and day 120 250 (SD:+/-150). Of 33 engrafted pts, 10 (30%) engrafted with a unit with pre-cryopreservation TNC < 2.5 x 107/kg, and 17 (51%) engrafted with a unit ≤ 5/8 HLA-allele matched. The cumulative incidence of day 100 grade II-IV acute GVHD was 46% (95%CI:29-61), and 23% (95%CI:11-38) had grade III-IV acute GVHD. 3-year chronic GVHD was 14% (95%CI:5-28). With a median 58 month (range 20-105) follow-up, the 3-year cumulative incidence of TRM was 11% (95%CI:4-24); deaths were due to graft failure (2), HHV-6 encephalitis (1), and viral pneumonia (1). Relapse at 3-years was 20% (95%CI:9-35): 2 AML CR1 (one FLT-3 ITD, one M7), one previously refractory AML, and 4 ALL (2 CR1, 1 CR2, 1 CR3). None of the 4 pts transplanted with MRD+ relapsed. Three-year DFS was 68% (95%CI:50-81), with no difference based on diagnosis (p = 0.25, Figure), TBI-based cytoreduction (p = 0.68), or non-European ancestry (p = 0.24). Conclusions: Despite high-risk disease and grafts with a very high degree of donor-recipient HLA-allele mismatch, the low TRM and relapse rates after pediatric DCBT are striking, with either TBI-based or chemotherapy-only conditioning. Although young children could have adequate single-unit grafts, a significant percentage will not. Therefore, DCBT remains an important consideration, especially for children of ethnic minorities.

Disclosures:
Nothing To Disclose