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- Bjorklund, AT, et al.
(författare)
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Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation
- 2016
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 196:3, s. 1400-1411
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Tidskriftsartikel (refereegranskat)abstract
- Acute and latent human CMV cause profound changes in the NK cell repertoire, with expansion and differentiation of educated NK cells expressing self-specific inhibitory killer cell Ig-like receptors. In this study, we addressed whether such CMV-induced imprints on the donor NK cell repertoire influenced the outcome of allogeneic stem cell transplantation. Hierarchical clustering of high-resolution immunophenotyping data covering key NK cell parameters, including frequencies of CD56bright, NKG2A+, NKG2C+, and CD57+ NK cell subsets, as well as the size of the educated NK cell subset, was linked to clinical outcomes. Clusters defining naive (NKG2A+CD57−NKG2C−) NK cell repertoires in the donor were associated with decreased risk for relapse in recipients with acute myeloid leukemia and myelodysplastic syndrome (hazard ratio [HR], 0.09; 95% confidence interval [CI]: 0.03–0.27; p < 0.001). Furthermore, recipients with naive repertoires at 9–12 mo after hematopoietic stem cell transplantation had increased disease-free survival (HR, 7.2; 95% CI: 1.6–33; p = 0.01) and increased overall survival (HR, 9.3; 95% CI: 1.1–77, p = 0.04). Conversely, patients with a relative increase in differentiated NK cells at 9–12 mo displayed a higher rate of late relapses (HR, 8.41; 95% CI: 6.7–11; p = 0.02), reduced disease-free survival (HR, 0.12; 95% CI: 0.12–0.74; p = 0.02), and reduced overall survival (HR, 0.07; 95% CI: 0.01–0.69; p = 0.02). Thus, our data suggest that naive donor NK cell repertoires are associated with protection against leukemia relapse after allogeneic HSCT.
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- Bjorklund, AT, et al.
(författare)
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NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:13, s. 2686-2694
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK)–cell alloreactivity in recipients of hematopoietic stem cell grafts from HLA-identical siblings is intriguing and has suggested breaking of NK-cell tolerance during the posttransplantation period. To examine this possibility, we analyzed clinical outcomes in a cohort of 105 patients with myeloid malignancies who received T cell–replete grafts from HLA-matched sibling donors. Presence of inhibitory killer cell immunoglobulin-like receptors (KIRs) for nonself HLA class I ligands had no effect on disease-free survival, incidence of relapse, or graft-versus-host disease. A longitudinal analysis of the NK-cell repertoire and function revealed a global hyporesponsiveness of NK cells early after transplantation. Functional responses recovered at approximately 6 months after transplantation. Importantly, NKG2A− NK cells expressing KIRs for nonself HLA class I ligands remained tolerant at all time points. Furthermore, a direct comparison of NK-cell reconstitution in T cell–replete and T cell–depleted HLA-matched sibling stem cell transplantation (SCT) revealed that NKG2A+ NK cells dominated the functional repertoire early after transplantation, with intact tolerance of NKG2A− NK cells expressing KIRs for nonself ligands in both settings. Our results provide evidence against the emergence of alloreactive NK cells in HLA-identical allogeneic SCT.
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- Lindahl, H, et al.
(författare)
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Lineage-specific early complete donor chimerism and risk of relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
- 2022
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 57:5, s. 753-759
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Tidskriftsartikel (refereegranskat)abstract
- Recipient–donor chimerism is routinely analyzed after allogeneic hematopoietic stem cell transplantation (HSCT) to monitor engraftment and graft rejection. For malignancies, chimerism can also be used to screen for disease relapse post-HSCT but methodology and interpretation of results are not standardized and likely depend on underlying diagnosis. We have implemented highly sensitive and accurate methodologies for chimerism analysis for the purpose of improving relapse prediction. Here, we report an exploratory retrospective analysis of clinical routine chimerism results from all 154 HSCTs for acute myeloid leukemia (AML) performed at our center during the years 2015–2020 with the aim of suggesting a clinically useful threshold at which risk of relapse is high. Relapse was not reliably predicted based on single elevated chimerism values obtained before time of overt relapse. However, early complete donor chimerism, here defined as recipient DNA < 0.2% in CD33+ cells in any blood or bone marrow sample taken during the first 60 days after HSCT, correlated inversely with relapse during the observation time (log-rank test P = 0.033). We propose that achievement of complete chimerism determined early after HSCT using sensitive methods can be used for risk-stratification of AML patients.
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