کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2101327 1546262 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases
چکیده انگلیسی


• Transfusion-related alloimmunization is a barrier to engraftment of HSCT.
• Expression of CD2 is up-regulated on memory T cells.
• Alefacept, a recombinant LFA-3/IgG1 fusion protein, targets CD2+ cells.
• We conducted a pilot study of alefacept preconditioning and HSCT in children with marrow failure.
• Alefacept was associated with full donor engraftment and depletion of CD2hi T cells and NK cells.

Transfusion-related alloimmunization is a potent barrier to the engraftment of allogeneic hematopoietic stem cells in patients with nonmalignant diseases (NMDs). Memory T cells, which drive alloimmunization, are relatively resistant to commonly used conditioning agents. Alefacept, a recombinant leukocyte function antigen-3/IgG1 fusion protein, targets CD2 and selectively depletes memory versus naive T cells. Three multiply transfused pediatric patients with NMD received a short course of high-dose i.v. alefacept (.25 mg/kg/dose on days −40 and −9 and .5 mg/kg/dose on days −33, −26, −19, and −12) before undergoing unrelated allogeneic transplant in the setting of reduced-intensity pretransplant conditioning and calcineurin inhibitor–based post-transplant graft-versus-host disease (GVHD) prophylaxis. Alefacept infusions were well tolerated in all patients. Peripheral blood flow cytometry was performed at baseline and during and after alefacept treatment. As expected, after the 5 weekly alefacept doses, each patient demonstrated selective loss of CD2hi/CCR7−/CD45RA− effector memory (Tem) and CD2hi/CCR7+/CD45RA− central memory (Tcm) CD4+ and CD8+ T cells with relative preservation of the CD2lo Tem and Tcm subpopulations. In addition, depletion of CD2+ natural killer (NK) cells also occurred. Neutrophil recovery was rapid, and all 3 patients had 100% sorted (CD3/CD33) peripheral blood donor chimerism by day +100. Immune reconstitution (by absolute neutrophil, monocyte, and lymphocyte counts) was comparable with a cohort of historical control patients. All 3 patients developed GVHD but are all now off immune suppression and >2 years post-transplant with stable full-donor engraftment. These results suggest that alefacept at higher dosing can deplete both memory T cells and NK cells and that incorporating CD2-targeted depletion into a reduced-intensity transplant regimen is feasible and safe in heavily transfused patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 21, Issue 10, October 2015, Pages 1845–1852
نویسندگان
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