Reconstitution of Natural Killer Cells in HLA-Matched HSCTafter Reduced-Intensity Conditioning: Impact on ClinicalOutcome

Caroline Pical-Izard, Roberto Crocchiolo, Samuel Granjeaud, Eloise Kochbati, Sylvaine Just-Landi, Christian Chabannon, Coralie Frassati, Christophe Picard, Didier Blaise, Daniel Olive, Cyril Fauriat

Research output: Contribution to journalArticlepeer-review

Abstract

Recent advances in the development of reduced-intensity conditioning (RIC) have allowed a broader range of patients to access allogeneic hematopoietic stem cell transplantation (HSCT). Reconstitution of an effective immune system post-transplant, including natural killer (NK) cells, is critical for both tumor control and infectious disease control or prevention. The development and functions of NK cells in such settings remain elusive. Here we analyzed NK cell development in HLA-matched HSCT from related or unrelated donors, after RIC that included antithymocyte globulin (N=45 patients). Our data reveal that NK cells quickly recover after RIC-HSCT, irrespective of donor type. Rapidly re-emerging NK cells, however, remain immature for more than 6months. Effector functions resemble that of immature NK cells because they poorly produce IFN-γ and TNF-α in response to target cell stimulation, despite a rapid acquisition of degranulation ability and MIP-1β production. Strikingly, rapid reconstitution of cytokine production correlates with a lower relapse incidence (P=01) and a better survival rate (P

Original languageEnglish
Pages (from-to)429-439
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • HLA-matched
  • NK cells
  • NK functions
  • Reduced-intensity conditioning
  • Stem cell transplantation

ASJC Scopus subject areas

  • Transplantation
  • Hematology
  • Medicine(all)

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