title: Beneficial effect of the CXCL12-3'A variant for patients undergoing hematopoietic stem cell transplantation from unrelated donors.
abstract: The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (p<0.1) while recipient age and donor-recipient gender relation were not significant. Moreover, CXCL12-3'-A-positive patients were less prone to early HHV-6 reactivation (2/34 vs. 19/69, p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome of unrelated HSCT.
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. Electronic address: bogunia@iitd.pan.wroc.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Mizia
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Polak
authors.affiliation: Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gronkowska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Nowak
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
authors.forename: Sławomira
authors.initials: S
authors.lastname: Kyrcz-Krzemień
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Markiewicz
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Dzierżak-Mietła
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Koclęga
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Sędzimirska
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Suchnicki
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Duda
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Lange
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Mordak-Domagała
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kościńska
authors.affiliation: Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Wiesław Wiktor
authors.initials: WW
authors.lastname: Jędrzejczak
authors.affiliation: Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kaczmarek
authors.affiliation: Medical University, Gdansk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Medical University, Gdansk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kucharska
authors.affiliation: Department of Paediatric Hematology, Oncology and Transplantology, Medical University, Lublin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
authors.affiliation: Department of Paediatric Hematology, Oncology and Transplantology, Medical University, Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Drabko
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Hałaburda
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Tomaszewska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Mika-Witkowska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Witkowska
authors.affiliation: Department of Transplantation, University Children's Hospital, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Goździk
authors.affiliation: Department of Transplantation, University Children's Hospital, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Mordel
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wysoczańska
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Jaskula
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D054377:Chemokine CXCL12 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D015654:Herpesvirus 6, Human / Q000502:physiology; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D014775:Virus Activation; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: CXCL12 polymorphism; Graft-versus-host disease; Hematopoietic stem cell transplantation from alternative donors; Toxicity; Viral reactivation