Myeloablative Double-Unit Cord Blood Transplantation (CBT) in Pediatric Patients with High-Risk Acute Leukemia Demonstrates Encouraging Disease-Free Survival with Both TBI and Chemotherapy-Only-Based Conditioning

• Published in: Blood 2014-12, Vol.124 (21), p.2578-2578
• Main Authors: Scaradavou, Andromachi, Lubin, Marissa N, Hilden, Patrick, Boulad, Farid, Curran, Kevin J., Kobos, Rachel, Prockop, Susan E., O’Reilly, Richard J., Tonon, Jo-Ann, Byam, Courtney, Steinherz, Peter G, Shukla, Neerav, Hasan, Aisha, Renaud, Thomas M., Zakak, Nicole, Kernan, Nancy A., Barker, Juliet N.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.2578.2578

Introduction: Double-unit CBT (DCBT) in adult patients (pts) with hematologic malignancies has been associated with high rates of disease-free survival (DFS) but its role in children is controversial. Methods: We investigated DCBT in children with high-risk acute leukemia following TBI or chemotherapy-based myeloablative cytoreduction. Outcomes of consecutive DCBT pts transplanted 10/2005-2/2013 as their first allograft were evaluated. Results: Thirty-five pts [median age 7.5 yrs (range 0.8-18), median weight 28 kg (range 8-75)] were transplanted. Seventeen had acute myelogenous or biphenotypic leukemia (AML): 6 in CR1 (one each with M7, secondary 5q- MDS, FLT-3 ITD mutation, Ph+, Down syndrome with positive MRD, or germline mutation CEBPa), 8 in CR2 (one with MLL positive MRD), 2 in aplasia, and one in CR3. Seventeen pts had ALL: 10 in CR1 [3 Ph+ (one with MRD), 2 T-cell ALL, one MLL, one L3 disease, and 3 multiple inductions], 4 in CR2, and 3 in CR3. One pt had CML (imantinib resistant, accelerated phase with MRD). Thirty-one percent were CMV seropositive and 69% had non-European ancestry. Conditioning was cyclophosphamide/fludarabine/TBI 1375 cGy (N=21, 60%), or in the very young or those with prior radiation a chemotherapy-based regimen was used (N=14, 40%, 10 with clofarabine/thiotepa/melphalan and 4 with busulfan/melphalan/thiotepa). GVHD prophylaxis was with calcineurin-inhibitor/mycophenolate mofetil. Units had a donor-recipient 4-6/6 HLA-A,-B antigen,-DRB1 allele match, a cryopreserved total nucleated cell (TNC) dose >1.5 x 107/kg/unit, and were albumin reconstituted for pts >20 kg or washed for smaller pts. 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). The median platelet recovery in 31 evaluable pts was 51 days (range 39-299). Immune recovery was prompt with a mean absolute CD4+ count of 201 (SD:+/-180) at day +60, and 250 (SD:+/-150) at day +120. The engrafting unit had a median infused TNC dose of 3.9 x 107/kg (range 0.9-12.8) and 10/33 (30%) pts engrafted with a unit that had a pre-cryopreservation TNC