Feasibility and safety of allogeneic ex vivo activated-NK cell infusion after matched related hematopoietic stem cell transplantation: Preliminary results of a prospective phase I trial

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S16
Author(s):  
B. Calmels ◽  
R. Devillier ◽  
S. Guia ◽  
B. Mfarrej ◽  
S. Furst ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Phase I Trial ◽  
Nk Cell ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Prospective Phase

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.

A Phase I Trial of High-Dose Chemotherapy Combining Topotecan plus Cyclophosphamide with Hematopoietic Stem Cell Transplantation for Ovarian Cancer: The ITOV 01bis Study

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 15-22
Author(s):  
Frédéric Selle ◽  
Patricia Pautier ◽  
Catherine Lhommé ◽  
Patrice Viens ◽  
Michel Fabbro ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Phase I Trial ◽  
Recurrent Ovarian Cancer ◽  
Intensive Chemotherapy ◽  
Hematopoietic Stem

Background: Dose-intensive chemotherapy with hematopoietic stem cell transplantation has been evaluated as a salvage treatment for recurrent ovarian cancer, but its benefit has not yet been demonstrated. In a previous phase I trial, we reported the feasibility of administering topotecan as a salvage regimen. Methods: Twenty-one patients were treated with escalating doses of topotecan associated with a fixed dose of cyclophosphamide. Results: The maximum tolerated dose was established at 9.0 mg/m2 on a 5-day regimen, analogously to what was reported for topotecan monotherapy. One toxic death from septic shock and multiorgan failure occurred. Although hematopoietic toxicities were overcome by peripheral blood stem cell transplantation, superior nonhematological toxicities were observed as compared to the initial trial. Conclusion: Response rates were generally short and survival rates were poor. Results of the ITOV 01bis study demonstrate that, in the setting of recurrent ovarian cancer, intensive chemotherapy based on topotecan-cyclophosphamide association is not currently clinically indicated.

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.

Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6123-6132 ◽  
Author(s):  
Richard K. Burt ◽  
Robert M. Craig ◽  
Francesca Milanetti ◽  
Kathleen Quigley ◽  
Paula Gozdziak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Crohn Disease ◽  
Ex Vivo ◽  
Activity Index ◽  
Clinical Relapse ◽  
Hematopoietic Stem

Abstract We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti–tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m2) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34+ selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.

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