scholarly journals Status of Donor-Recipient HLA Class I Ligands and Not the KIR Genotype Is Predictive for the Outcome of Unrelated Hematopoietic Stem Cell Transplantation in Beta-Thalassemia Patients

2007 ◽  
Vol 13 (11) ◽  
pp. 1358-1368 ◽  
Author(s):  
Giorgio La Nasa ◽  
Roberto Littera ◽  
Franco Locatelli ◽  
Claudio Giardini ◽  
Arianna Ventrella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hla Class I ◽  
Class I ◽  
Beta Thalassemia ◽  
Hematopoietic Stem

Killer Ig–like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 764-771 ◽  
Author(s):  
Lorenzo Moretta ◽  
Franco Locatelli ◽  
Daniela Pende ◽  
Emanuela Marcenaro ◽  
Maria Cristina Mingari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hla Class I ◽  
Class I ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Natural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell–depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such “alloreactive” NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.

scholarly journals What unrelated hematopoietic stem cell transplantation in thalassemia taught us about transplant immunogenetics

2016 ◽  
Vol 8 ◽  
pp. 2016048 ◽  
Author(s):  
Giorgio La Nasa ◽  
Adriana Vacca ◽  
Roberto Littera ◽  
Eugenia Piras ◽  
Sandro Orru ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Malignant Disease ◽  
Human Leukocyte ◽  
Beta Thalassemia ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cordon blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS) and thalassemia-free survival (TFS) rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD) remains the most important complication in unrelated HSCT in thalassemia, leading to considerable rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individuate appropriate strategies for its prevention and management. This review provides an overview on recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia.

Hepatocytes of Donor Origin in Recipients Liver, after Hematopoietic Stem Cell Transplantation in BetaThalassemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4063-4063
Author(s):  
Ardeshir Ghavamzadeh ◽  
Mehrzad Mirzania ◽  
Nahid Sedighi ◽  
Marjan Yaghmaie ◽  
Naser Kamalian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Beta Thalassemia ◽  
Hematopoietic Stem ◽  
Biopsy Specimens

Abstract Background Bone marrow and circulating stem cells contains stem cells with the potential to differentiate into mature cells of various organs. We determined whether stem cells transformed to hepathcytes. Methods Biopsy specimens from the liver were obtained from 11 patients who had undergone transplantation of hematopoietic stem cells from peripheral blood (8 patients) or bone marrow (3 patients). Four female patients had received transplants from a male donor and seven male patients had received transplants from a female donor.All patients had beta thalassemia major and fibrosis in biopsy specimens from the liver before hematopoietic stem-cell transplantation. Hematopoietic stem-cell engraftment was verified by short tandem repeat analysis. The biopsies were studied for the presence of donor-derived hepatocytes with the use of fluorescence in situ hybridization of interphase nuclei and immunohistochemical staining for CD45 (leukocyte common antigen), and a hepatocyte-specific antigen. Results All 11 recipients of sex-mismatched transplants showed evidence of complete hematopoietic donor chimerism. XY-positive hepatocytes accounted for 4 to 6.7 percent of the cells in histologic sections of the biopsy specimens of female patients. These cells were detected in liver tissue as early as 1 year and as late as 8.5 year after the hematopoietic stem cell transplantation. Conclusions Bone marrow and circulating stem cells can differentiate into mature hepatocytes in beta thalassemia major patients who undergone hematopoietic stem cell transplantation.

Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2594-2600 ◽  
Author(s):  
Dietrich W. Beelen ◽  
Hellmut D. Ottinger ◽  
Stanislav Ferencik ◽  
Ahmet H. Elmaagacli ◽  
Rudolf Peceny ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hla Class I ◽  
Class I ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Myeloid Leukemias

AbstractIt remains controversial whether alloreactive donor-derived natural killer (NK) cells display graft-versus-leukemia reactions after unmodified allogeneic hematopoietic stem cell transplantation (HSCT). The present study evaluated the role of inhibitory killer immunoglobulin–like receptor (KIR) ligand incompatibility using a well-defined and uniform setting of unmodified allogeneic HSCT in 374 patients with myeloid leukemias. The most striking finding was a significant heterogeneity in the 5-year estimates of hematologic leukemic relapse after human leukocyte antigen (HLA)–identical (n = 237; 22%), HLA class I–disparate (n = 89; 18%), and KIR ligand–incompatible transplantations (n = 48; 5%) (P < .04). Multivariate analysis confirmed that the relative relapse risk (RR) was influenced by HLA class I disparity alone (RR 0.49), but was lowest after HLA class I–disparate, KIR ligand–incompatible transplantations (RR 0.24) (P < .008). The primary graft failure rates, however, increased from 0.4% after HLA class I–identical to 2.3% after HLA class I–disparate, and to 6.3% after KIR ligand–incompatible transplantations, respectively (P < .02). Unlike some other reports, no beneficial effect of KIR ligand incompatibility on other major endpoints of allogeneic HSCT (transplantation-related mortality, and overall and event-free survival) was detectable in the present study. In conclusion, unmodified allogeneic HSCT from KIR ligand–incompatible donors provides a superior long-term antileukemic efficacy in patients with myeloid malignancies.

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