Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) in Children with Acute Leukemia: Risks and Benefits of Umbilical Cord Blood (CB) vs. Bone Marrow (BM).
Authors: Rubinstein Pablo , Eapen Mary , Stevens Cladd , Kurtzberg Joanne , Scaradavou Andromachi , Klein John , Horowitz Mary , Wagner John 
Published: April 2020

Though CB is an accepted alternative to BM for HSCT, the selection of CB over BM remains controversial. Therefore, we compared the results of 492 unrelated donor BM and 508 CB transplants performed in children &lt;16 years of age between 1995–2003. Median follow up was 45 and 59 months for CB and BM recipients, respectively. Compared to BM recipients, CB recipients were younger, less likely to be Caucasoid, more likely to have advanced disease, less likely to receive irradiation and more likely to receive cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Whereas, 7% of CB recipients were matched at HLA A, B (low resolution) and DRB1, 40%, 1-locus and 53%, 2 loci mismatched, respecively, 75% of BM recipients were matched and 25% mismatched at 1-locus. Neutrophil recovery at day 42 depended on graft type and cell dose: 97% with BM, 86% with matched CB, 79% with high cell dose (&gt;0.3 x 108/kg) CB graft mismatched at 1 or 2 loci and 64% with low cell dose (≤ 0.3 x 108/kg) CB grafts. Rates of grades 2–4 acute GVHD were 70% with mismatched BM, 50% with matched BM, 40% with mismatched CB and 20% with matched CB. Corresponding rates of chronic GVHD were 35%, 33%, 17% and 27%. The relative efficacy of CB and BM transplantation depended on HLA disparity and CB cell dose as shown in the Table below. Children receiving matched CB had significanlty lower risks of treatment failure and overall mortality than those receiving matched BM; children receiving high cell dose CB mismatched at 1 locus had risks similar to those receiving matched BM. Children receiving low cell dose CB mismatched at 1 locus and CB mismatched at 2 loci (any cell dose) had higher risks of treatment failure and mortality than matched BM recipients during the first 3 months after transplantation; among children surviving the first 3 months, subsequent risks were similar to children receiving BM. The 3-year probability of leukemia-free survival was highest after matched CB transplants (60%); LFS probabilities were similar with matched BM and high cell dose CB mismatched at 1 locus (40% and 41%, respectively). Probabilities were lower after mismatched BM, low cell dose CB mismatched at 1 locus and CB mismatched at 2 loci (30%, 36% and 33%, respectively). These data support use of matched CB grafts or CB mismatched at 1 locus with a high cell dose for children needing HSCT, whether or not a matched BM donor is available; low cell dose or 2-loci mismatched CB grafts may provide a reasonable alternative when a matched BM donor is not available or for those whose disease requires immediate transplantation.

Treatment failure Overall mortality N Relative Risk (95% CI) P-value Relative Risk (95% CI) P-value BM Matched 368 1.00 1.00 BM 1-Ag mismatched 123 1.26 (0.98–1.62) 0.07 1.22 (0.93–1.59) 0.15 CB matched 35 0.52 (0.30–0.92) 0.02 0.54 (0.30–0.97) 0.04 CB 1-Ag mismatched, high dose 157 0.95 (0.75–1.22) 0.71 0.96 (0.75–1.25) 0.78 CB 1-Ag mismatched, low dose 44     ≤ 3 months 1.85 (1.14–2.99) 0.01 2.35 (1.44–3.83) 0.001     &gt;3 months 0.69 (0.35–1.35) 0.35 0.73 (0.37–1.42) 0.35 CB 2-Ag mismatched 266     ≤ 3 months 1.75 (1.36–2.60) &lt;0.001 2.06 (1.57–2.71) &lt;0.001     &gt;3 months 0.87 (0.65–1.16) 0.66 0.94 (0.70–1.25) 0.66