title: Graft engineering for allogeneic haploidentical stem cell transplantation.
abstract: Haploidentical stem cell transplantation has became a clinical reality in the last 10 years as it provides the chance of transplant for about 50% of patients with hematological malignancies who do not have a matched related or unrelated donor. Proper graft preparation for this type of transplant is crucial and this paper analyses our work over the past decade in the search for the optimal graft processing procedure moving from E-rosetting and soybean agglutination, through a combination of negative or positive selection of hematopoietic stem cells to the current method of one-step positive selection. In preparing a graft for haploidentical transplant, three essential requisites must be met. It must contain (1) a megadose (>10 x 10(6) x kg recipient b.w.) of hematopoietic stem cells to overcome the HLA histocompatibility barrier; (2) very few T-lymphocytes (CD3+ cells < 3 x 10(4)/kg recipient b.w.) to prevent severe acute and chronic graft-versus-host disease (GvHD); (3) very few B-lymphocytes to prevent Epstein-Barr virus-related lymphoproliferative disorders. With current graft processing technologies based on positive selection of hematopoietic stem cells, these requirements can be met. A 70-80% hematopoietic stem cell recovery ensures the target megadose is achieved in over 70% of cases with a T-cell depletion of more than 4 logs and a B-cell depletion of over 3 logs. Progress in graft processing has ensured primary, sustained engraftment rates of over 90% and has significantly reduced the incidence of severe acute GvHD and EBV-related lymphoproliferative disorders. Modern time-saving automated graft processing devices ensure reproducibility, reliability, and biological safety, which make widespread application of the haploidentical transplant currently feasible.
authors.affiliation: Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology, University of Perugia, Perugia, Italy. atabilio@unipg.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Tabilio
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Zei
authors.forename: Maria
authors.initials: M
authors.lastname: De Ioanni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Feliciana
authors.initials: F
authors.lastname: Battelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Iacucci Ostini
authors.forename: Stelvio
authors.initials: S
authors.lastname: Ballanti
authors.forename: Michele
authors.initials: M
authors.lastname: Cimminiello
authors.forename: Monia
authors.initials: M
authors.lastname: Capponi
authors.forename: Carla
authors.initials: C
authors.lastname: Silvani
authors.forename: Olivia
authors.initials: O
authors.lastname: Minelli
authors.forename: Katia
authors.initials: K
authors.lastname: Fettucciari
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Marconi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rosati
authors.forename: Antonella
authors.initials: A
authors.lastname: Santucci
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Ianni
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
mesh_terms: D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion / Q000295:instrumentation / Q000379:methods; D023822:Tissue Engineering / Q000379:methods*; D019737:Transplants