scholarly journals Hematopoietic stem cell transplantation: Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1

2016 ◽  
Vol 46 (6) ◽  
pp. 1511-1517 ◽  
Author(s):  
Claudia Alicata ◽  
Daniela Pende ◽  
Raffaella Meazza ◽  
Paolo Canevali ◽  
Fabrizio Loiacono ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Donor Selection ◽  
Hematopoietic Stem

Donor KIR3DL1 and HLA-B Allotypes Control Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 349-349
Author(s):  
Fabio Giglio ◽  
Ted A. Gooley ◽  
Jeffrey M Venstrom ◽  
Meighan M Gallagher ◽  
LiHua Hou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Donor Selection ◽  
Receptor Expression ◽  
Hematopoietic Stem ◽  
High Affinity ◽  
Selection Algorithms

Abstract Abstract 349 Natural killer (NK) cells are vital in the control of viral infection and malignancy, in particular AML. Affinity strength between NK receptors and their HLA ligands control both NK effector function and degree of NK inhibition. Differences in binding affinity between allotypes of the NK receptor KIR3DL1 and allotypes of its ligand HLA-Bw4 depend on the expression levels of the receptor and the amino acid residue at position 80 in the ligand. Because receptor-ligand affinities are associated with differences in HIV control, we hypothesized that different affinities between donor KIR3DL1 and donor-recipient HLA-Bw4 allotypes would impact the risk for AML relapse following allogeneic hematopoietic stem cell transplantation (HCT). Methods: We evaluated 299 AML patients who underwent allogeneic HCT from an unrelated donor between 1995 and 2002. Clinical data, HLA allotyping, and donor DNA were provided by the CIBMTR. KIR3DL1 allotyping was executed using PCR- and sequence-based methods. Donors were segregated into those with high-, low- and null expressing KIR3DL1 allele groups [3DL1-H (n=130), 3DL1-L (n=69), 3DL1-N (n=82)] and HLA-B allele groups (Bw6/Bw6, Bw4-I80, Bw4-T80). 3DL1-N genotypes are predictive of poor surface expression and were analyzed separately. Patients and donors were matched at 9 or 10 HLA loci in all cases, with only 3 donor-patient pairs mismatched for HLA-Bw4 ligands. Affinity cohorts were compared using Cox regression for the time-to-event outcomes of relapse and overall mortality (OM). Kaplan-Meier estimates of overall survival and cumulative incidence estimates of relapse were obtained. Results: Recipients of 3DL1-H and 3DL1-L donors were analyzed for high and low-affinity associations with post-HCT AML relapse. Among patients with a 3DL1-H donor, those transplanted from donors with the low-affinity KIR/HLA allotype combination 3DL1-H/Bw4-T80 had lower risk of relapse when compared to those with the high-affinity 3DL1-H/Bw4-I80 combination (HR 0.22; p=.003, Table) and even moreso when compared to the extra-high affinity combinations of 3DL1-H with Bw4-I80-B*2702 or B*57 (HR 0.10; p<.001). Among patients with 3DL1-L donors, those with the low-affinity KIR-HLA combination 3DL1-L/Bw4-I80 were associated with lower relapse in patients when compared to those with the high-affinity 3DL1-L/Bw4-T80 combination (HR 0.21; P=.009). Among the combined patient groups, low-affinity combinations were strongly associated with lower relapse (HR 0.24; P<.001; FigA) and lower mortality (HR 0.62; P=.03; FigB) in patients compared to the high-affinity combinations. Lack of HLA-Bw4 ligand (HLA-Bw6/Bw6) provided intermediate protection from AML relapse compared to patients in the high-affinity group (HR 0.39; P= .002; Fig 1A). Donor 3DL1-N genotypes, predictive of poor receptor expression on the NK cell surface, were not associated with HCT outcome. Conclusions: Protection from relapse of AML after unrelated HCT is associated with the affinity between donor KIR3DL1 and HLA-Bw4, ranging from the highly protective low-affinity donor KIR3DL1/HLA-Bw4 allotype combinations to the susceptible and “super-susceptible” effects of high- and extra-high affinity KIR/HLA combinations. These data support the consideration of KIR and HLA allotype combinations in stem cell donor selection algorithms to minimize the risk of AML relapse following HCT. Because >95% of donors are positive for KIR3DL1 and 69% of patients are positive for HLA-Bw4, incorporation of KIR3DL1/HLA-Bw4 allotypes in donor selection algorithms is a highly relevant and feasible goal. Disclosures: No relevant conflicts of interest to declare.

scholarly journals DONOR SELECTION: IMMUNOGENETICS AND HISTOCOMPATIBILITY

JBMTCT ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 22-27
Author(s):  
Sociedade Brasileira de TMO SBTMO ◽  
Margareth Afonso Torres ◽  
Gisele Fabianne Rampim ◽  
Juliana Fernandes Cardoso ◽  
Carmem Vergueiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Marrow Transplantation ◽  
Donor Selection ◽  
Hematopoietic Stem ◽  
Blood And Marrow Transplantation ◽  
Brazilian Society

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

scholarly journals The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiao-hui Zhang ◽  
Jing Chen ◽  
Ming-Zhe Han ◽  
He Huang ◽  
Er-lie Jiang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Donor Selection ◽  
Chinese Society ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Selection For

AbstractThe consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.

scholarly journals Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

Chimerism ◽  
2012 ◽  
Vol 3 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Gurvinder Kaur ◽  
Neeraj Kumar ◽  
Ramya Nandakumar ◽  
Chowphi C. Rapthap ◽  
Gaurav Sharma ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hair Follicles ◽  
Donor Selection ◽  
Hematopoietic Stem ◽  
Selection For
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