title: A prospective analysis of immune recovery in children following allogeneic transplantation of t-cell-depleted or non-T-cell-depleted hematopoietic cells from HLA-disparate family donors.
abstract: Transplantation of HLA-disparate hematopoietic stem cells from related donors is an alternative for the treatment of patients lacking an HLA-matched family or unrelated donor. In the cases of a single HLA antigen disparity, extensive T-cell depletion (TCD) is not required, yet antithymocyte globulin (ATG) must be administered to prevent GvHD or graft rejection. The major concern after HLA-mismatched transplants remains immune reconstitution. Therefore, we prospectively studied the recovery of lymphocyte subsets among 22 children transplanted from partially HLA-matched family donors. We compared two groups of patients: (1) the TCD group included children (n = 1.3) who received grafts after TCD (MACS) due to an HLA disparity for more than one antigen; (2) The non-TCD group included children with either one HLA-mismatched antigen, n = 7; or more than one disparate antigen (n = 2) who received T-cell-repleted grafts and ATG. The study demonstrated rapid NK cell reconstitution among the TCD group. TCD compromised T-cell reconstitution, thus preventing GvHD, but resulting in a higher incidence of severe infectious complications, graft rejection, and disease relapse. Increasing mixed chimerism required the application of donor T-cell addbacks, thus potentiating the risk of GvHD. Primary graft rejection occurred in eight children, who required further transplants. In the non-TCD group faster T-cell reconstitution (predominantly CD3+CD8+ cells) resulted in a lower rate of relapse and infection, yet a higher rate of GvHD, including two fatal cases. Due to improved immune reconstitution, in spite of an increased risk of GvHD, non-TCD transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors.
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Wroclaw, Wroclaw, Poland. kk@pedhemat.am.wroc.pl
authors.forename: K
authors.initials: K
authors.lastname: Kalwak
authors.forename: I
authors.initials: I
authors.lastname: Mosoń
authors.forename: J
authors.initials: J
authors.lastname: Cwian
authors.forename: E
authors.initials: E
authors.lastname: Gorczyńska
authors.forename: J
authors.initials: J
authors.lastname: Toporski
authors.forename: D
authors.initials: D
authors.lastname: Turkiewicz
authors.forename: E
authors.initials: E
authors.lastname: Latos-Grazyńska
authors.forename: A
authors.initials: A
authors.lastname: Chybicka
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D019520:Living Donors; D008212:Lymphocyte Depletion; D008297:Male; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents