**Author details**

far greater degrees of HLA mismatch, CBT is still associated with lower incidences and severity of acute and chronic GvHD than HSCT from adult donors [124]. According to the recent study of 143 patients in 2010, the rate of grade II or higher GvHD is only 9% among HLA-matched (n = 60) and 50% among HLA-mismatched (n = 18) patients [125]. Being less mature than stem cells from adult grafts, CB stem cells show lower alloreactivity and immunogenicity without increasing long-term relapse incidences [126]. Moreover, CB has other advantages including low contamination rate, easy storage and immediate accessibility via cryopreservation [125].

206 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

Together with its relatively lenient requirement for HLA matching, CB has been used commonly as an alternative source for transplantation. Indeed, one of the first cases to treat AD with CBT was performed due to lack of HLA-matched, appropriate adult stem cell source [127]. Raetz and colleagues performed myeloablative conditioning HSCT on a 5-year-old boy with severe Evans syndrome, which consists of immune thrombocytopenia and Coombspositive hemolytic anemia. The graft was a CB from an HLA-matched sibling with 3.85 × 107

remission. Acute GvHD prophylaxis regimen was with cyclosporine, with G-CSF initiated on day +1. The patient engrafted with an absolute neutrophil count (ANC) greater than 0.5 × 109

l on day +16. The following day, he developed symptoms of acute GvHD, with temperatures of up to 40°C, skin rash that on biopsy was consistent with GvHD and severe pulmonary insufficiency. He was intubated for 2 days and treated with high-dose steroids, with rapid resolution of symptoms. Platelet engraftment was delayed, with sustained platelets greater

from day +210. Reevaluation of his RBC antibody status revealed a DAT that was only microscopically positive by day +20 and negative on day +286. Anti-platelet antibodies were negative on day +115 and day +176. He had no evidence of response with cyclosporine pretransplant and no evidence of disease recurrence 2 months after discontinuation of cyclosporine and 4 months after discontinuation of prednisone. At the time of death, the patient was off all immunosuppression and had complete resolution of his autoimmune disease. However, the patient died unexpectedly from acute hepatic failure 9 months after transplantation [127].

Itamura et al. reported another case for a 48-year-old female patient with RA [128], who was subsequently diagnosed as having autoimmune hemolytic anemia (AIHA). Four months after the diagnosis of AIHA, she suddenly developed hemophagocytic syndrome (HPS) with disseminated intravascular coagulation (DIC) and *Staphylococcus aureus* bacteremia. Her HPS transiently improved after treatment, but relapsed 3 weeks later. Without an immediately available related adult donor, an unrelated donor CB graft was used for HSCT. The patient had HLA antibodies against multiple HLA class I antigens; however, the CB unit did not express HLA antigens reactive to her HLA antibodies and contained sufficient cell dose. HLA type of the CB graft was A\*02:06/A\*11:01, B\*40:06/B\*67:01, DRB1\*09:01/DRB1\*16:02 and that of the recipient was A\*11:01/A\*26:02, B\*40:06/B\*67:01, DRB1\*09:01/DRB1\*16:02. Four months after the onset of HPS, she received a CBT following a conditioning regimen of melphalan (40 

was used for the prophylaxis of GvHD. Engraftment of neutrophils ANC500 and platelets 20K occurred on days 14 and 32, respectively. Bone marrow examination on day 60 showed

/l by day +170. He was platelet independent from day +240 and RBC independent

CD34+ cells/kg patient infused, leading to complete

/day 5 days) and total-body irradiation. Tacrolimus

/

nucleated cells/kg patient and 0.96 × 105

than 30 × 109

mg/m2

/day 2 days), fludarabine (25 mg/m2

Christine Chow, Tracie Dang, Vincent Guo, Michelle Chow, Qingyu Li, Delon Te-Lun Chow, Elizabeth Rao, Tony Zeng, Baixiang Wang and Robert Chow\*

\*Address all correspondence to: rchow@cytetherapeutics.com

CyteTherapeutics, Inc., Irvine, CA, USA & Beijing, People's Republic of China
