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Pediatric Transplants

Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders

Abstract

This study was designed to determine the safety of a nonmyeloablative regimen in patients with primary immunodeficiency disorders (PID) who had infections, organ dysfunction or other risk factors that precluded conventional hematopoietic cell (HC) transplant. Fourteen patients received HLA-matched related (n=6) or unrelated (n=8) HC grafts from marrow (n=8), peripheral blood mononuclear cells (n=5) or umbilical cord blood (n=1), either without conditioning (n=1), or after 200 cGy total body irradiation alone (n=3) or with 90 mg/m2 fludarabine (n=10). All patients were given postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Mixed (n=5) or full (n=8) donor chimerism was established in 13 patients, and one patient rejected the graft. Eight patients developed acute grade III (n=1) and/or extensive chronic GVHD (n=8). With a median follow-up of 4.9 (range, 0.7–8.1) years, the 3-year overall survival, event-free survival and transplant-related mortality were 62, 62 and 23%, respectively. Correction of immune dysfunction was documented in 8 of 10 patients with stable donor engraftment. These preliminary results indicated that this approach was associated with stable donor engraftment and a low incidence of early mortality and, thus, can be considered for certain high-risk patients with PID. However, there was a risk of GVHD, which is an undesirable outcome for this group of patients.

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Acknowledgements

We thank Paul Hoffmeister, Chris Davis, Gary Schoch, Deborah Bassuk and Heather Hildebrant for data management; the research nurses Mary Hinds and John Sedgwick; the nursing and clinical staff for their dedicated care of patients; and Bonnie Larson, Helen Crawford, Debbie Sessions, Karen Carbonneau and Sue Carbonneau for help with manuscript preparation.

Supported in part by Grants CA78902, CA15704, HL36444, HD17427, HD043376, CA076930 and HL085288 from the NIH, Bethesda, MD, USA and grants from the Immunodeficiency Foundation and Jeffrey Modell Foundation. LB is the recipient of an award from the Fighting Children's Cancer Foundation.

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Correspondence to A E Woolfrey.

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Burroughs, L., Storb, R., Leisenring, W. et al. Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders. Bone Marrow Transplant 40, 633–642 (2007). https://doi.org/10.1038/sj.bmt.1705778

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