The Effect of KIRs Expression Profile in Donor/Recipient Pairs in HLA-Identical Sibling Hematopoietic Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4017-4017
Author(s):  
Xiaoai Wei ◽  
XiaoWen Tang ◽  
Yufeng Feng ◽  
Ziling Zhu ◽  
Jun He ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Expression Profile ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Matched Group

Abstract Abstract 4017 Objective: We investigated the distribution characteristics of KIRs expression profile in donor/recipient pairs with acute leukemia (AL) receiving HLA-identical sibling hematopoietic stem cell transplantation (sib-HSCT). We further explored the effect of KIRs expression profile in donor/recipient pairs on clinical outcome, including dynamics of donor T cell and NK cell engraftment. Methods: The genotypes of donor/recipient KIRs were determinated by polymerase chain reaction- sequence specific primer (PCR-SSP) for 80 pairs of donor/recipient receiving HLA-identical sibling hematopoietic stem cell transplantation. The multiple short tandem repeat (STR) PCR was used to evaluate the status of engraftment of donor T cells and NK cells at +14 days, 21 days, 28 days, 60 days and 90 days after transplantation in 24 cases. Results: 1. In 80 pairs of donor/recipient: (i) the KIRs were completely identical in 57.5% of donor/recipient pairs; (ii) the donors' KIRs contained the recipients' in 13.75% pairs; (iii) the recipients' KIRs contained the donors' in 17.5% of pairs; (iv) the KIRs were completely different in 11.25% pairs. The graft versus host (GVH) direction KIR-matched group was 75%. The percentage of group donor B/X and group donor A/A was 50%, respectively. 2. Comparing the patients from GVH direction KIR-matched and mismatched group, the incidence of acute (a) GVHD was 60% and 30%, respectively (P =0.0222), and 2-year OS was 62.96% and 94.12%, respectively (P =0.0492). Particularly, grade III-IV aGVHD rate of KIR-matched group was higher than that of non-KIR matched group(15% vs 0%). 3. Donor B/X group had a higher 2-year OS and 2-year relapse-free survival (RFS) compared with donor A/A group (89.23% vs 49.57%, P =0.0159, and 90% vs 59.71%, P =0.0239, respectively). Patients with three or less aKIRs had a lower 2-year OS (58.9% vs 92.44%, P =0.0338) and a lower RFS (65.14% vs 92.59%, P =0.0398), compared with patients with more aKIR. 4. Sequential monitoring of chimerism status of donor NK-cells in 24 cases revealed that on day+14, the percentage of full donor NK cells chimerism was higher in non-KIR matched patients than that of KIR matched patients (85.7% vs 52.9%, P =0.0456). Conclusions: Donor KIR genotype appears to have a direct impact on aGVHD, OS and RFS. Therefore, donor KIR genotype should be evaluated as an outcome predictor of the HLA-identical sib-HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Human NK Cells in Autologous Hematopoietic Stem Cell Transplantation for Cancer Treatment

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1589
Author(s):  
Ane Orrantia ◽  
Iñigo Terrén ◽  
Gabirel Astarloa-Pando ◽  
Olatz Zenarruzabeitia ◽  
Francisco Borrego
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Biology ◽  
Nk Cell ◽  
Hematopoietic Stem ◽  
Autologous Hsct

Natural killer (NK) cells are phenotypically and functionally diverse lymphocytes with the ability to recognize and kill malignant cells without prior sensitization, and therefore, they have a relevant role in tumor immunosurveillance. NK cells constitute the main lymphocyte subset in peripheral blood in the first week after hematopoietic stem cell transplantation (HSCT). Although the role that NK cells play in allogenic HSCT settings has been documented for years, their significance and beneficial effects associated with the outcome after autologous HSCT are less recognized. In this review, we have summarized fundamental aspects of NK cell biology, such as, NK cell subset diversity, their effector functions, and differentiation. Moreover, we have reviewed the factors that affect autologous HSCT outcome, with particular attention to the role played by NK cells and their receptor repertoire in this regard.

scholarly journals Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation

2019 ◽  
Vol 3 (24) ◽  
pp. 4312-4325 ◽  
Author(s):  
Xiang-Yu Zhao ◽  
Xing-Xing Yu ◽  
Zheng-Li Xu ◽  
Xun-Hong Cao ◽  
Ming-Rui Huo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Nk Cell ◽  
K562 Cells ◽  
Inhibitory Receptors ◽  
Hematopoietic Stem

Abstract The rate and extent of natural killer (NK)–cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand. NK-cell responsiveness was tuned commensurate with the number of inhibitory receptors from the donor. When both donor and host expressed the 3 major KIR ligands (HLA-C1, HLA-C2, and HLA-Bw4), NK cells expressing 3 inhibitory receptors (KIR2DL1/2DL3/3DL1) reached the maximum responsiveness against K562 cells compared with those NK cells expressing only 1 or 2 inhibitory receptors. When donor and host HLA both expressed all ligands for donor inhibitory KIRs, patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) showed the lowest recurrence rate after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In conclusion, this study demonstrates that when both donors and hosts present all the KIR ligands for donor KIRs, reconstituted NK cells achieve better functional education and contribute to least relapse among patients. This observation study was registered at www.clinicaltrials.gov as #NCT02978274.

scholarly journals IL-2 and Anti-TGF-β Promote NK Cell Reconstitution and Anti-tumor Effects after Syngeneic Hematopoietic Stem Cell Transplantation

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3189 ◽  
Author(s):  
Maite Alvarez ◽  
Cordelia Dunai ◽  
Lam T. Khuat ◽  
Ethan G. Aguilar ◽  
Isabel Barao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immune Cells ◽  
Nk Cell ◽  
Continuous Treatment ◽  
Hematopoietic Stem

The failure of autologous hematopoietic stem cell transplantation (HSCT) has been associated with a profound immunodeficiency that follows shortly after treatment, which renders patients susceptible to opportunistic infections and/or cancer relapse. Thus, given the additional immunosuppressive pathways involved in immune evasion in cancer, strategies that induce a faster reconstitution of key immune effector cells are needed. Natural killer (NK) cells mediate potent anti-tumor effector functions and are the first immune cells to repopulate after HSCT. TGF-β is a potent immunosuppressive cytokine that can impede both the development and function of immune cells. Here, we evaluated the use of an immunotherapeutic regimen that combines low dose of IL-2, an NK cell stimulatory signal, with TGF-β neutralization, in order to accelerate NK cell reconstitution following congenic HSCT in mice by providing stimulatory signals yet also abrogating inhibitory ones. This therapy led to a marked expansion of NK cells and accelerated NK cell maturation. Following HSCT, mature NK cells from the treated recipients displayed an activated phenotype and enhanced anti-tumor responses both in vitro and in vivo. No overt toxicities or adverse effects were observed in the treated recipients. However, these stimulatory effects on NK cell recovery were predicated upon continuous treatment as cessation of treatment led to return to baseline levels and to no improvement of overall immune recovery when assessed at later time-points, indicating strict regulatory control of the NK cell compartment. Overall, this study still demonstrates that therapies that combine positive and negative signals can be plausible strategies to accelerate NK cell reconstitution following HSCT and augment anti-tumor efficacy.

scholarly journals Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma

2016 ◽  
Vol 50 (4) ◽  
pp. 402-408 ◽  
Author(s):  
Matevz Skerget ◽  
Barbara Skopec ◽  
Darja Zontar ◽  
Peter Cernelc
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
T Regulatory Cells ◽  
Nk Cell ◽  
Hematopoietic Stem ◽  
Cell Counts

Abstract Background Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation. Patients and methods In total 48 patients were prospectively enrolled in three different mobilization regimens; (i) filgrastim (20), (ii) pegfilgrastim (19) and (iii) cyclophosphamide + filgrastim (9). Lymphocytes, CD16+/56+ natural killer and CD4+/CD25high T regulatory cells were determined by flow cytometry. Results We found a statistically significant difference between the mobilization regimens. Cyclophosphamide reduced lymphocyte and natural killer (NK) cell counts on collection day (lymphocytes 1.08 × 109/L; NK cells 0.07 × 109/L) compared to filgrastim (lymphocytes 3.08 × 109/L; NK cells 0.52 × 109/L) and pegfilgrastim (lymphocytes 3 × 109/L; NK cells 0.42 × 109/L). As a consequence lymphocyte and NK cell counts were also lower in the leukapheresis products following cyclophosphamide mobilization regimen (lymphocytes 50.1 × 109/L; NK cells 4.18 × 109/L) compared to filgrastim (lymphocytes 112 × 109/L; NK cells 17.5 × 109/L) and pegfilgrastim (lymphocytes 112 × 109/L; NK cells 14.3 × 109/L). In all mobilization regimens T regulatory cells increased 2-fold on collection day, regarding the base line value before mobilization. There was no difference in T regulatory cell counts between the regimens. Conclusions Mobilization with cyclophophamide reduces the number of mobilized and collected lymphocytes and NK cells as compared to mobilization with growth factors only and results in their delayed reconstitution following autologous hematopoietic stem cell transplantation. We found no difference between filgrastim and pegfilgrastim mobilization.

scholarly journals Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study

2020 ◽  
Vol 9 (11) ◽  
pp. 3502
Author(s):  
Tereza Dekojová ◽  
Lucie Houdová ◽  
Jiří Fatka ◽  
Pavel Pitule ◽  
Pavel Ostašov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Nk Cell ◽  
Ex Vivo ◽  
Post Transplantation ◽  
Hematopoietic Stem

Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands—HLA(Human Leukocyte Antigen) class I molecules—are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients’ clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.

Femoral Head Necrosis In Three Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5489-5489
Author(s):  
Gang Zhao ◽  
Zhi Li ◽  
Jiahua Ding ◽  
Jun Wang ◽  
Zhengping Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Femoral Head ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Femoral Head Necrosis ◽  
Hematopoietic Stem

Abstract Femoral head necrosis (FHN) is one of common complications after hematopoietic stem cell transplantation (HSCT). It impacts on patients' normal life with severe pain. To investigate FHN after allogeneic HSCT, We performed retrospective analyses. Since 2003, our department has conducted 98 cases of allogeneic hematopoietic stem cell transplantation for patients with hematologic diseases. Chemotherapy regimens and transplant conditioning regimen before transplantation were steroid-free. FHN occurred in 3 out of 98 cases. The 3 patients were treated with steroid for preventing graft versus host disease (GVHD) after transplantation. However, all the three patients suffered from GVHD, which was cured with steroidal medication subsequently. Then, symptoms of FHN come out and were significantly improved after conservative treatment in all the three patients. The occurrence of FHN might be associated with GVHD and corticosteroids prescription. Early prevention might be helpful in reducing the incidence and improving outcomes. Disclosures: No relevant conflicts of interest to declare.

Evaluation of Blood Group Conversion Following ABO-Incompatible Hematopoietic Stem Cell Transplantation (HCT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1557-1557 ◽  
Author(s):  
Esther HL Chan ◽  
Thiow Christofer ◽  
Susan TT Lim ◽  
Lip Kun Tan ◽  
Michelle Poon
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Blood Group ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Body Tissues ◽  
Group Data

Abstract Title: Evaluation of blood group conversion following ABO-incompatible Hematopoietic Stem Cell Transplantation (HCT). Background: While there have been a number of reports concerning the influence of AB0 incompatibility on hematopoietic transplantation (HCT) outcomes, data evaluating post-HCT blood group conversions following ABO incompatible transplants remains extremely limited. Methods: We performed a single centre retrospective analysis of 97 patients undergoing major or minor or bidirectional ABO-mismatched bone marrow (BM), peripheral blood (PB), and cord blood (CB) hematopoietic stem cell transplantation (HCT) between January2005 – April 2014, in whom engraftment had occurred and blood group data was available. The aim of the study was to analyse the red cell ABO phenotype (forward grouping) and levels of anti-A/B antibodies (reverse grouping) in these patients following the ABO-mismatched transplants. Results: 97 patients transplanted between January 2004 and April 2014 were included in the analysis. There were 40 (41%) matched sibling, 32 (33%) matched unrelated and 25 (26%) CB transplants. Indications for HSCT included both haematological malignancies (n=87) and benign conditions (n=10). Of these donor recipient pairs, there were 44 (45%) minor, 39 (40%) major and 14 (15%) bidirectional ABO mismatches. All patients had achieved full donor type chimerism at the time of analysis. Analysis of post –HCT blood group conversion was performed in each of the three groups. Amongst the major mismatch patients (n=39), all had conversion of RBC phenotype to donor ABO phenotype and loss of their host derived anti-donor ABO antibodies. Interestingly, in the minor mismatch patients who were tested (n=44), all the patients had conversion of their RBC phenotype, but 43 out of 44 patients failed to produce recipient directed anti-ABO antibodies. Similarly in the bidirectional mismatch group, all 14 patients converted to donor ABO phenotype, but none produced recipient directed anti-ABO antibodies. Conclusion: In one of the largest study looking at this issue, our study demonstrated the lack of a development of recipient directed anti A/B antibodies despite complete donor chimerism in the majority (1 out of 58) of patients undergoing minor or bidirectional ABO-mismatched HSCT. We postulate that this phenomenon may be due to the donor B cell tolerance against host ABO antigen due to the presence of host A and B antigens within other body tissues. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5835-5849 ◽  
Author(s):  
Jeffrey I. Cohen ◽  
Elaine S. Jaffe ◽  
Janet K. Dale ◽  
Stefania Pittaluga ◽  
Helen E. Heslop ◽  
...  
Keyword(s):  
United States ◽  
Stem Cell ◽  
B Cells ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
The United States ◽  
Hematopoietic Stem

Abstract Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoietic stem cell transplantation in the United States. Most cases of CAEBV have been reported from Japan. Unlike CAEBV in Japan, where EBV is nearly always found in T or natural killer (NK) cells in tissues, EBV was usually detected in B cells in tissues from our patients. Most patients presented with lymphadenopathy and splenomegaly; fever, hepatitis, and pancytopenia were common. Most patients died of infection or progressive lymphoproliferation. Unlike cases reported from Japan, our patients often showed a progressive loss of B cells and hypogammaglobulinemia. Although patients with CAEBV from Japan have normal or increased numbers of NK cells, many of our patients had reduced NK-cell numbers. Although immunosuppressive agents, rituximab, autologous cytotoxic T cells, or cytotoxic chemotherapy often resulted in short-term remissions, they were not curative. Hematopoietic stem cell transplantation was often curative for CAEBV, even in patients with active lymphoproliferative disease that was unresponsive to chemotherapy. These studies are registered at http://www.clinicaltrials.gov as NCT00032513 for CAEBV, NCT00062868 and NCT00058812 for EBV-specific T-cell studies, and NCT00578539 for the hematopoietic stem cell transplantation protocol.

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