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

被引:32
作者
Burroughs, L. M.
Storb, R.
Leisenring, W. M.
Pulsipher, M. A.
Loken, M. R.
Torgerson, T. R.
Ochs, H. D.
Woolfrey, A. E.
机构
[1] Fred Hutchinson Canc Res Ctr, Dept Med, Div Oncol, Seattle, WA 98109 USA
[2] Univ Washington, Sch Med, Seattle, WA 98195 USA
[3] Univ Utah, Sch Med, Salt Lake City, UT USA
[4] Hematol Inc, Seattle, WA USA
关键词
hematopoietic cell transplantation; nonmyeloablative conditioning; primary immunodeficiency disorders; severe combined immunodeficiency; bone marrow transplantation;
D O I
10.1038/sj.bmt.1705778
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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/m(2) 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.
引用
收藏
页码:633 / 642
页数:10
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