Abstract
Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for transplant-eligible patients with multiple myeloma (MM). Among factors that influence outcome after autoHSCT, it has been suggested that the number of natural killer (NK) cells plays an important role. However, the impact that different NK cell subsets and their phenotype could have in disease progression after autoHSCT are less clear. For this reason, we have phenotypically and functionally characterized NK cells during immune system reconstitution after autoHSCT in 54 MM patients. Shortly after leukocyte recovery, an extensive redistribution of NK cell subsets occurs in these patients. In addition, NK cells undergo a profound phenotypic change characterized, among others, by their increased proliferative capacity and immature phenotype. Importantly, MM patients who showed lower frequencies of the mature highly differentiated NKG2A-CD57+ NK cell subset at +30 and +100 days after autoHSCT experienced superior progression-free survival and had a longer time to the next treatment than those with higher frequencies. Our results provide significant insights into NK cell reconstitution after autoHSCT and suggest that the degree of NK cell maturation after autoHSCT affects the clinical outcome of MM patients treated with this therapeutic strategy.
Highlights
Autologous hematopoietic stem cell transplantation is a worldwide-established treatment option for a diverse group of hematological malignances, including multiple myeloma (MM)
The absolute number of natural killer (NK) cells was maintained at the same levels after that; the values were significantly higher than what was observed in Sample 1 (S1) and sample 2 (S2) (Figure 1A)
We have examined the reconstitution of NK cells in patients with MM who had undergone autoHSCT by analyzing different NK cell subsets, their phenotype and functionality, in order to determine an association with the clinical outcome postautoHSCT
Summary
Autologous hematopoietic stem cell transplantation (autoHSCT) is a worldwide-established treatment option for a diverse group of hematological malignances, including multiple myeloma (MM). Natural killer (NK) cells are the first to recover during immune reconstitution after transplantation and are recognized as the main lymphocyte subset in ALC-15 that affects outcome after autoHSCT [2]. NK cells are a crucial part of the innate immune system, being classified within the family of the innate lymphoid cells [3]. One of their main features is the ability to recognize and eliminate virusinfected and malignant cells without prior sensitization. In autoHSCT and allogeneic hematopoietic stem cell transplantation (alloHSCT), both an early human CMV reactivation and/or adaptive NK cell expansion have been associated with reduced relapse [8,9,10]. Few studies have performed a comprehensive analysis of how different NK cell subsets and their phenotype change during NK cell reconstitution after autoHSCT and the association of these alterations with the clinical outcome of these patients
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