Unrelated Umbilical Cord Blood Transplant for Children with Leukemia: Single or Double Unit Transplant

Abstract

Unrelated umbilical cord blood transplant (UCBT) was performed in 24 children (16 M, 8 F) with leukemia in a single institution from June 1998 to May 2008. The leukemia types were Acute Lymphoblastic Leukemia (ALL, n=13), Acute Myeloid Leukemia (AML, n=9) and Juvenile Myelomonocytic Leukemia (JMML, n=2). The disease status was CR2 in 13, CR3/4 in 3, refractory or relapse in 8. Fifteen patients received single unit (SU) and 9 patients received double unit (DU) UCBT. The mean age and body weight were 5.7 ± 3.7 year and 19.5 ± 7.9 kg for SU, 7.7 ± 4.0 year and 24.6 ± 9.9 kg for DU, respectively. The sources of cord blood units were from local public CB bank (n=20) and 4 overseas public CB banks (n=4). The cord blood units were not more than 2 HLA antigen mismatches from the patients, and the DU cord blood were also not more than 2 antigen mismatches between each other. The minimal requirement was nucleated cell (NC) dose > 2.5×107/kg for SU, and > 3.7 ×107/kg for DU. The conditioning was TBI based for ALL and busulphan-based for myeloid leukemia. ATG was routinely included except in 5 patients. The engraftment rate was 70.8% for the whole group, and 66.7% and 77.8% for SU and DU, respectively. All the 4 overseas UCBT failed to engraft and the engraftment rate for local CB bank units was 85%. The 2 JMML had failed engraftment, one received SU and 1 DU. There was no significant difference in the transplanted cell dose for SU and DU (combined dose), NC 6.2±3.8×107/kg vs 8.2±3.5×107/kg, CD34 cell 5.0±7.2 ×105/kg vs 3.8±1.3×105/kg, respectively. However patients who had successful engraftment received higher cell dose, NC 7.9±3.9×107/kg vs 4.5±1.8×107/kg (p=0.042), CD34 cell 5.4±6.3 ×105/kg vs 2.2±1.6×105/kg (p=0.073), respectively. All the 9 DU UCBT showed signs of engraftment with donor DNA detected, but two did not achieve neutrophil engraftment and subsequently failed engraftment. On the first chimerism study on Day 7–10, 3 had mixed chimerism (MC, 50–60% vs 40–50%) and 2 became single donor complete chimerism (CC) in the second week study, one had persistent MC up to 1 month but required second transplant for failed neutrophil engraftment. Six patients had CC with single CB unit since the week 1 and were maintained in 5, and another one had failed neutrophil engraftment. Finally 7 DU UCBT had sustained CC with single donor unit, however the finally successfully engrafted unit had lower CD34 cell dose as compared to the non-engrafted unit (1.5±0.5×105/kg vs 2.4±1.1 ×105/kg, p=0.004), and the NC dose of the 2 units in DU was similar (3.6±1.7.×107/kg vs 4.4±1.8×107/kg (p=0.042). There was no difference in the degree of HLA mismatch between the engrafted and non-engrafted units of DU. The neutrophil engraftment was more rapid with SU as compared with DU, 14.5 vs 19.7 days, p=0.021, the platelet engratment and number of red cell and platelet transfusion was not different. All those with engraftment developed acute GVHD, and the incidence of grade III–IV was similar between SU and DU (33.3% vs 28.6%), and none died from AGVHD. Nine patients died of non-engraftment or transplant related mortality, 3 from leukemia relapse and 12 were alive (7 patients > 3 years). The 2-year survival after UCBT was 47%. In conclusion, DU cord blood could achieve a higher NC dose, but the engraftment of DU was always single unit and 33% had transient MC in the very early week of UCBT. The DU approach may enhance the engraftment of the finally engrafted unit even that had a lower CD34 cell dose.