title: Graft dysfunction and delayed immune reconstitution following haploidentical peripheral blood hematopoietic stem cell transplantation.
abstract: For many children with life-threatening hematological diseases, hematopoietic stem cell transplantation (HSCT) is the only curative option. In children lacking a matched related or unrelated donor and with the certainty that, left untreated, death will ensue alternative donors must be sought. Haplo-identical peripheral blood stem cell transplantation (PBSCT) from a healthy parent is a feasible alternative. To reduce the risk of fatal graft-versus-host disease (GvHD) as a complication of transplant across major histocompatibility antigens, intense T-cell depletion is required. Large numbers of purified, cytokine mobilized peripheral stem cells (the so-called mega-dose concept) are required to compensate for the significantly increased risk of either graft failure or early rejection. In our unit, despite this approach, graft dysfunction has, in a significant group of children, proved problematic and, despite salvage attempts at re-transplantation, usually fatal. In children with hematological malignant disease, our overall relapse-free survival is 41%. However, successful transplant outcome has been associated with considerable delays in immune reconstitution that can be implicated in subsequent viral reactivation. We are investigating new strategies to improve the outcome of haplo-identical PBSCT, which may allow us to offer this form of treatment to more children requiring urgent HSCT.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands. l.m.ball@lumc.nl
authors.forename: L M
authors.initials: LM
authors.lastname: Ball
authors.forename: A C
authors.initials: AC
authors.lastname: Lankester
authors.forename: R G M
authors.initials: RG
authors.lastname: Bredius
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: M J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: R M
authors.initials: RM
authors.lastname: Egeler
mesh_terms: D000293:Adolescent; D018952:Antigens, CD34; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D006402:Hematologic Diseases / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007107:Immune System; D007223:Infant; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D020127:Recovery of Function; D016879:Salvage Therapy / Q000379:methods / Q000401:mortality; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018952:Antigens, CD34