Publication Date:
2013-11-15
Description:
Background Despite enhanced tolerability of HLA mismatch, the reduced number of HSPC in an UCB graft limits the use of this stem cell source because of delayed hematopoietic recovery and increased risk of graft failure, particularly in adults. For this reason, we explored the effectiveness of SR1, an aryl hydrocarbon receptor antagonist, in the presence of cytokines to expand HSPC ex vivo prior to transplantation. Patients and Methods Nine patients with high-risk lympho-hematopoietic malignancy and two partially HLA (4-6/6)-matched UCB units were treated with cyclophosphamide 120 mg/kg, fludarabine 75 mg/m2 and total body irradiation 1320 cGy followed by double UCB transplantation. Unit1 (the unmanipulated larger of the two units) was infused followed by SR1-expanded UCB HSPC (derived from CD34 selected Unit2 cells cultured for 15 days) as well as rethawed CD34 negative Unit2 cells. GVHD prophylaxis was cyclosporine A and mycophenolate mofetil. Results Culture in the presence of SR1 resulted in a median of 248-fold (range, 66-446) expansion of CD34+ cells. The median number of CD34+ cells and CD3+ cells infused for Unit1 and Unit2 were 0.3 x 106/kg (range, 0.2-0.9) and 11.0 x 106/kg (range, 1.4-48.9), and 7.3 x 106/kg (range, 4.6-10.6) 2.8 x 106/kg (range, 0.4-4.9), respectively. There were no infusional toxicities noted. Based on a presumed graft-graft interaction, the HSC835 product predominated in 5 of 9 patients and resulted in sustained hematopoiesis for a median follow up of 303 days (range 140-401). The median time to neutrophil recovery (days to absolute neutrophil count of ≥500/uL) was shorter in recipients of HSC835 (i.e., 16 days [range, 6-23] versus 24 days [range, 22-30]) with the speed of neutrophil recovery correlating with the number of CD34+ cells infused (r2 = -0.87, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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