title: Higher CD34(+) and CD3(+) cell doses in the graft promote long-term survival, and have no impact on the incidence of severe acute or chronic graft-versus-host disease after in vivo T cell-depleted unrelated donor hematopoietic stem cell transplantation in children.
abstract: The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+) and CD3(+) cell doses on survival and incidence of severe graft-versus-host disease (GVHD) in 187 children who underwent UD hematopoietic cell transplantation with the use of in vivo T cell depletion (antithymocyte globulin or CAMPATH-1H). HLA typing was performed at the "high-resolution" level. Patients receiving > or =10 x 10(6) CD34(+) cells/kg and > or =4 x 10(8) CD3(+) cells/kg had better overall and disease-free survival. Multivariate analysis has shown that both infused CD34(+) cell dose <10 x 10(6)/kg and CD3(+) cell dose <4 x 10(8)/kg were independent risk factors for mortality (relative risk [RR] 1.8 and 1.71, P = .009 and .016, respectively). Regarding disease-free survival, multivariate analysis has revealed another independent risk factor for poor outcome apart from the 2 earlier-mentioned cell doses, which was the use of donors mismatched at 2 HLA antigens or 3 HLA allele/antigens (RR 2.5, P = .004). In age groups 0-10 years and 10-20 years, CD34(+) cell doses higher than the age-adjusted median dose clearly favored survival. Higher infused doses of CD34(+) and CD3(+) cells did not result in an increased rate of severe GVHD. The use of mismatched donors was the only independent risk factor for the incidence of severe acute GVHD (RR 2.2, P = .046). The report demonstrates for the first time in a pediatric cohort, that higher doses of transplanted CD34(+) and CD3(+) cells lead to an improved survival without an increased risk of severe GVHD. The study findings may be limited to the population of patients receiving in vivo T cell depletion, which is now broadly used in unrelated donor setting in Europe.
authors.affiliation: Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Poland. kk@pedhemat.am.wroc.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kałwak
authors.forename: Julita
authors.initials: J
authors.lastname: Porwolik
authors.forename: Monika
authors.initials: M
authors.lastname: Mielcarek
authors.forename: Ewa
authors.initials: E
authors.lastname: Gorczyńska
authors.forename: Joanna
authors.initials: J
authors.lastname: Owoc-Lempach
authors.forename: Marek
authors.initials: M
authors.lastname: Ussowicz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dyla
authors.forename: Jakub
authors.initials: J
authors.lastname: Musiał
authors.forename: Dominika
authors.initials: D
authors.lastname: Paździor
authors.forename: Dominik
authors.initials: D
authors.lastname: Turkiewicz
authors.forename: Alicja
authors.initials: A
authors.lastname: Chybicka
mesh_terms: D000293:Adolescent; D000367:Age Factors; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation / Q000706:statistics & numerical data; D017252:CD3 Complex / Q000032:analysis*; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D047589:Leukocyte Reduction Procedures; D019520:Living Donors; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation / Q000706:statistics & numerical data; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex