Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction

Katharina Fleischhauer, Franco Locatelli, Marco Zecca, Maria Grazia Orofino, Claudio Giardini, Piero De Stefano, Andrea Pession, Angela Maria Iannone, Carlo Carcassi, Elisabetta Zino, Giorgio La Nasa

Research output: Contribution to journalArticle

Abstract

The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for β-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLA-matched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n = 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n = 17) or in the graft-versus-host (GvH; n = 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR = 7.42; 95% CI = 1.29-42.68; P = .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR = 5.15; 95% CI = 1.58-16.82; P = .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.

Original languageEnglish
Pages (from-to)2984-2992
Number of pages9
JournalBlood
Volume107
Issue number7
DOIs
Publication statusPublished - Apr 1 2006

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Transplantation (surgical)
Unrelated Donors
Thalassemia
Hematopoietic Stem Cell Transplantation
Graft Rejection
Stem cells
Grafts
Transplants
Dichlororibofuranosylbenzimidazole
Immunogenetics
Control Groups
HLA-A Antigens
HLA-B Antigens
T-cells
Multivariate Analysis
Tissue Donors
T-Lymphocytes
Survival
Incidence
HLA-DPB1 antigen

ASJC Scopus subject areas

  • Hematology

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Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction. / Fleischhauer, Katharina; Locatelli, Franco; Zecca, Marco; Orofino, Maria Grazia; Giardini, Claudio; De Stefano, Piero; Pession, Andrea; Iannone, Angela Maria; Carcassi, Carlo; Zino, Elisabetta; La Nasa, Giorgio.

In: Blood, Vol. 107, No. 7, 01.04.2006, p. 2984-2992.

Research output: Contribution to journalArticle

Fleischhauer, Katharina ; Locatelli, Franco ; Zecca, Marco ; Orofino, Maria Grazia ; Giardini, Claudio ; De Stefano, Piero ; Pession, Andrea ; Iannone, Angela Maria ; Carcassi, Carlo ; Zino, Elisabetta ; La Nasa, Giorgio. / Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction. In: Blood. 2006 ; Vol. 107, No. 7. pp. 2984-2992.
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abstract = "The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for β-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLA-matched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n = 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n = 17) or in the graft-versus-host (GvH; n = 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR = 7.42; 95{\%} CI = 1.29-42.68; P = .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR = 5.15; 95{\%} CI = 1.58-16.82; P = .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.",
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AU - Fleischhauer, Katharina

AU - Locatelli, Franco

AU - Zecca, Marco

AU - Orofino, Maria Grazia

AU - Giardini, Claudio

AU - De Stefano, Piero

AU - Pession, Andrea

AU - Iannone, Angela Maria

AU - Carcassi, Carlo

AU - Zino, Elisabetta

AU - La Nasa, Giorgio

PY - 2006/4/1

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N2 - The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for β-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLA-matched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n = 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n = 17) or in the graft-versus-host (GvH; n = 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR = 7.42; 95% CI = 1.29-42.68; P = .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR = 5.15; 95% CI = 1.58-16.82; P = .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.

AB - The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for β-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLA-matched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n = 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n = 17) or in the graft-versus-host (GvH; n = 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR = 7.42; 95% CI = 1.29-42.68; P = .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR = 5.15; 95% CI = 1.58-16.82; P = .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.

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