Unrelated placental/umbilical cord blood cell (UCBC) transplantation in children with high-risk sickle cell disease (SCO)

The lack of HLA-matehed healthy sibs limits the potentially curative use of hematopoietic cell transplantation (HCT) for high-risk SCO in children and adults. Successful unrelated UCBC transplantation (UCBCT) has been reported in pediatrie patients (pts) with neoplastic, immunologie, metabolic and other hematologie disorders but has not been previously described in pts with high-risk SCO. We performed unrelated UCBCTs in 2 pts with SCO who had had cerebrovascular accidents (CVAs) and were on chronic transfusion and chelation programs. Pt 1 was a 12-year-old male (weight 34.3 kg) and pt 2 was a 6-year-old female (weight 15.7 kg); neither had HLA-matched healthy related HCT donors. The protocol for unrelated UCBCT was approved by the institutional review boards, with case review and approval by an ethics/advisory committee. Conditioning for UCBCT included busulfan (1 mg/kg q6hr × 16 doses), cyclophosphamide (50 mg/kg/d × 4 d) and anti-thymocyte globulin (30 mg/kg/d x 3 d). Each UCBC unit was from a male donor and was matched with the pt at 4 of 6 HLA loci (mismatched at HLA-B and -DRB1 in pt 1 and at HLA-A and -B in pt 2). Mononuclear and CD34+ cell doses, respectively, were 1.7×10⁷/kg and 1.8× 10⁵/kg in pt 1 and 5.7 × 10⁷/kg and 2.7 x 10⁵/kg in pt 2. Supportive care after UCBCT included seizure prophylaxis with phenytoin and transfusions to maintain hemoglobin >10 g/dl and platelets >50 × 10⁹/l. Absolute neutrophils exceeded 0.5 x 10⁹/l at 23 and 37 days, platelets exceeded 50 x 10⁹/l at 71 and 53 days, and red cell transfusion independence occurred at 7 mo and 2.6 mo after UCBCT in pts 1 and 2, respectively. Hemoglobin S has been absent in both pts since 2-3 mo after UCBCT. Pt 1 developed grade 2 gastrointestinal acute graft-versus-host disease (GVHD) and extensive cutaneous and hepatic chronic GVHD that responded to treatment with cyclosporine, corticosteroids and mycophenolate mofetil. Pt 2 had grade 1 cutaneous acute GVHD that responded to corticosteroids. Both pts are alive with donor hematopoietic engraftment and without new manifestations of SCO at 21.1 and 3.3 months, respectively, after unrelated UCBCT. We conclude that unrelated UCBCT establishes normal erythropoiesis, prevents further symptoms, and eliminates the need for chronic transfusions and chelation in children with SCO who lack healthy histocompatible related HCT donors. The morbidity and potential mortality of unrelated UCBCT, however, strongly suggest that the procedure should be limited at this time to SCO pts with high-risk complications such as CVAs.