Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

Biol Blood Marrow Transplant. 2015 Oct;21(10):1845-52. doi: 10.1016/j.bbmt.2015.06.005. Epub 2015 Jun 19.


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 CD2(hi)/CCR7(-)/CD45RA(-) effector memory (Tem) and CD2(hi)/CCR7(+)/CD45RA(-) central memory (Tcm) CD4(+) and CD8(+) T cells with relative preservation of the CD2(lo) 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.

Trial registration: NCT01319851.

Keywords: Alefacept; Conditioning; Hematopoietic stem cell transplantation; Nonmalignant diseases; Rejection.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alefacept
  • Anemia, Aplastic / therapy
  • Blood Component Transfusion / statistics & numerical data
  • Bone Marrow Transplantation*
  • CD2 Antigens / immunology
  • Child
  • Cord Blood Stem Cell Transplantation*
  • Dyskeratosis Congenita / therapy
  • Fanconi Anemia / therapy
  • Female
  • Graft Survival
  • Graft vs Host Disease / etiology
  • Historically Controlled Study
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Infant
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Depletion / methods*
  • Male
  • Pilot Projects
  • Recombinant Fusion Proteins / supply & distribution
  • Recombinant Fusion Proteins / therapeutic use*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Transplantation Conditioning*
  • Unrelated Donors


  • CD2 Antigens
  • Recombinant Fusion Proteins
  • Alefacept

Associated data