Donor KIR B Haplotype Is Associated with a Increased Rate of Leukemia Relapse and Worse Overall Survival after HLA Match Sibling Pediatric Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5926-5926
Author(s):  
Antonio Pérez-Martínez ◽  
Isabel Martinez ◽  
Jaime Valentin ◽  
Lucia Fernandez ◽  
Vicario José Luis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Nk Cell ◽  
Univariate Analysis ◽  
Blood Stem Cell ◽  
Leukemia Relapse

Abstract Introduction Graft versus leukemia (GvL) effect after hemotopoietic stem cell transplantation (HSCT) is mediated by donor immune cells recovery. Natural Killer (NK) cell alloreactivity is controlled by the interaction of activatory receptors and inhibitory killer-immunoglobulin-like receptors (KIRs) with major histocompatibility locus class I antigens on the leukemia cells. Haploidentical setting is a plattform for NK cell alloreactivity however HLA identical setting remains unclear. Methods and Patients We performed KIR-genotyping of HLA-identical sibling donors in 35 pediatric CD34 selection peripheral blood stem cell transplantations to identify genetic factors affecting leukemia relapse and overall survival. Univariate analysis of leukemia relapse and KIR genotyping was performed in order to identify independent variables predictive of outocome for pediatric acute lymphoblastic leukemia (ALL), (n=20) and acute myeloblastic leukemia (AML), (n=15). Results Donor B haplotype was observed in 21 cases (60%). Statistical analysis shown that donor B haplotype was associated with significantly more relapse in leukemia pediatric patients (38% vs. 0%) and worse overall survival (40% vs. 7%). Further analysis revealed that 2DL5a, 2DS3 and 2DS5 were associated with an increased rate of leukemia relapse (47% vs. 6%, 54% vs. 10% and 58% vs. 13%, respectively) and 2DL5a, 2DS1 and 3DS1 were associated with a worse overall survival (48% vs. 6%, 64% vs. 10% and 58% vs. 13%, respectively). No difference was observed in patients KIR haplotype or donor-recipient KIR haplotype mismatch. Conclusion In our study, which included only reduced intensity conditioning without antithymocyte globulin followed by related peripheral blood stem cell transplantation, we found a significant worse impact of donor KIR B haplotype in stem cell transplantation outcome. Our results suggest that donor KIR B haplotype (2DL5a, 2DS3 and 2DS5) increases leukemia relapse and also donor KIR B haplotype (2DL5a, 2DS1 and 3DS1) confer significant survival damage to HLA-identical sibling HSCT. Figure 1. Donor KIR genotyping (2DL5A, 2DS1 and 3DS1) impacts in overall survival. Figure 1. Donor KIR genotyping (2DL5A, 2DS1 and 3DS1) impacts in overall survival. Disclosures No relevant conflicts of interest to declare.

The Studies on the T-Cell Receptor Repertoire Diversity and Flow Cytometric Analysis in a Patient with MAS/HPS after Unrelated Peripheral Blood Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4970-4970
Author(s):  
Xin Du ◽  
Yangqiu Li ◽  
Suxia Geng ◽  
Jianyu Weng ◽  
Zesheng Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Nk Cell ◽  
Flow Cytometric Analysis ◽  
Blood Stem Cell ◽  
Flow Cytometric

Abstract Macrophage activation syndrome (MAS) /Hemophagocytic syndrome (HPS) is characterized by proliferation of activated macrophages under conditions such as infection(C Clin Infect Dis 2004)lymphoma(Aouba A Am J Hematol 2004), autoimmune disease(Kaneko K Clin Rheumatol 2005), solid organ transplantation(Akamatsu N,Transplant Proc 2006;). There have been several reports of MAS /HPS after hematopoietic stem cell transplantation, involving not only allogeneic,but also autologous transplantation(Sreedharan A Bone Marrow Transplantation,2006). Generally, MAS /HPS is a cytokine-related disorder.But at present, its clinical characteristics remain unknown. We firstly study here the T-cell receptor repertoire diversity and flow cytometric analysis in MAS /HPS after unrelated peripheral blood stem cell transplantation. The CDR3 of TCR Vα and Vβ subfamily genes were amplified in peripheral blood mononuclear cells from the patient with MAS/HPS after unrelated peripheral blood stem cell using RT-PCR for detection of the distribution of TCR Vα and Vβ repertoire, the PCR products were further analyzed by genescan technique for the CDR3 size, to evaluating clonality of the detectable TCR Vα and VβT cells. Lymphocyte subsets in the peripheral blood were detected by monoclone antibody and flow cytometry including T lymphocyte subsets and NK cells. Flow-cytometric analysis showed CD56+ CD16+ cell 68.65% and CD3+ cell 11.79% in the lymphocyte population;CD16+CD69+ cell 68.51% and CD25+CD16+ cell 31.59% in NK cell. In the T lymphocytic subsets, CD25 + CD3+ cell 62%; CD69+CD3+ cell 75.81%; CD25CD4+ cell 0.81%,CD25CD8+ cell 3.48%; CD69CD4+ cell 0.31%, CD69+CD8+ cell 16.86%.The results show that the main activated lymphocytes is NK cell in patient at diagnosed with MAS/HPS. Of interest, it was only after the addition of high-dose IVIG 1g/kg/d for two days (Ostronoff et al BMT2006) to the treatment that MAS remitted. There are 23 Vα and 15Vβ subfamily T cells could be identified in this time, and the clonal expansion T cells could be found in TCR Vα5, 13, 20; TCR Vβ4, 11, 15 and 21subfamilies. Billiau et al (Blood 2005)describes the immunohistochemical findings on liver tissues from 5 children with MAS in the context of a different type of hemophagocytic syndrome (HPS) in liver transplantation. This study is the first directly to substantiates the presumed immunopathogenesis of MAS by documenting in situ expression of IFN-γ+ by activated CD8+ lymphocytes, and of IL-6 and TNF-α+ by hemophagocytosing macrophages, on liver tissues of patients with MAS. We found no evidence of potential infectious, autoimmune or malignant triggers of R-HPS in our patient, despite extensive investigations. We conclued that the skew distribution and clonal expansion of TCR Vα and Vβ subfamily T cells underscore the primary role of T cells in the pathogenesis of MAS/HPS.

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