Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies.

Published

Journal Article

The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft-versus-host disease (GvHD). We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin in order to expedite immune reconstitution after a CD3-depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3(+) T-cells, T-cell receptor (TCR) excision circle counts, TCRbeta repertoire diversity and natural killer (NK)-cells during the first 4 months post-transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.

Full Text

Duke Authors

Cited Authors

  • Chen, X; Hale, GA; Barfield, R; Benaim, E; Leung, WH; Knowles, J; Horwitz, EM; Woodard, P; Kasow, K; Yusuf, U; Behm, FG; Hayden, RT; Shurtleff, SA; Turner, V; Srivastava, DK; Handgretinger, R

Published Date

  • November 2006

Published In

Volume / Issue

  • 135 / 4

Start / End Page

  • 524 - 532

PubMed ID

  • 17010105

Pubmed Central ID

  • 17010105

International Standard Serial Number (ISSN)

  • 0007-1048

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2141.2006.06330.x

Language

  • eng

Conference Location

  • England