A Single Center Experience with Allogeneic Sibling Umbilical-Cord-Blood Transplantation in Children with Malignant and Non-Malignant Disease.

To study the outcome of allogeneic sibling umbilical-cord-blood transplantation (CBT) in children in China, we studied the records of 38 recipients of cord blood from HLA-identical siblings from 1998 through 2004. The mean age at transplant was 10.3+/−5.5 years. Diseases of the patients were leukemia (28), neuroblastoma (3), severe aplastic anaemia (3) and inborn errors of metabolism (four). A volume of 76–208 ml of cord blood was collected from sibling infants soon after delivery. HLA antigens were identical in 32 and one to three antigens mismatched in six. The patients received busulphan and cyclophosphamide as conditioning, and antithymocyte globulin was given to prevent graft rejection. The median number of collected nucleated cells was 3.5 x 10⁷/kg nucleated cells (range, 2.0 to 10.2). T-cell reconstitution was evaluated by using combined approaches of phenotyping analysis of lymphocytes and assessment of ex vivo thymic function by measuring T-cell receptor (TCR) rearrangement excision circles (TRECs). The overall survival is 89% at the median observation time of 72 months. The median time for neutrophil engraftment (absolute neutrophil count >500/mm³) was 16 days (range, 10 to 41days). The median time to become transfusion independent after CBT was 27 days for platelets (range, 15 to 54) and was 28 days for packed red blood cells (range, 19 to 128). Acute GVHD (aGVHD)was observed in 20/38 patients and involved only skin in 16 patients, skin and liver or gut in 2 patients and all 3 organs in another 2 patients. Seventeen of 20 patients had grade 1 to 2 aGVHD toxicity, whereas 3 patients experienced grade 3 to 4 aGVHD. Chronic GVHD (cGVHD) developed in 12 patients. Acute transplant related mortality was 5.5%. Cause of death was persisting non-engraftment till day +100 after transplant. Late mortality occurred in 2 patients: one cGVHD associated haemorrhage 22 months after CBT and one cGVHD associated septicaemia 4 years after CBT. Immunologic reconstitution demonstrated that CBT resulted in consistent and stable T-, B- and natural killer (NK) cell development. The kinetics of development was such that T-cell development occurred between 65 to 180 days. Initial T-cell engraftment consisted predominantly of CD45RO⁺, CD3⁺, and CD4⁺ T cells, and at 12 to 24 months changed to CD45RA⁺, CD3⁺, and CD4⁺ T cells, indicating de novo maturation of T cells. During the first 5 months after transplantation, TCR repertoires were highly abnormal and TREC values low. However, in a longer follow-up (one years or more after transplantation) TREC values and TCR diversity increased and became normal. This data confirms that CBT still should be the first treatment choice if an HLA-identical sibling is available.