Increase of interleukin-18 serum levels after engraftment correlates with acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation

Scholl, Sebastian; Sayer, Herbert G.; Mügge, Lars-Olof; Kasper, Christoph; Pietraszczyk, Marko; Kliche, Kay-Oliver; Clement, Joachim H.; Höffken, K.

doi:10.1007/s00432-004-0603-6

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…Murine studies have attempted to demonstrate a role of IL-1b in acute GVHD [23], but pediatric studies are currently lacking. No significant differences in known cytokines implicated in acute GVHD, such as IL-2 [19,24,25], IL-17 [26], IL-10 [27][28][29][30], IL-18 [31][32][33], TNF-a [34][35][36], and IFN-g [37,38], were observed between patients with isolated engraftment syndrome and acute GVHD in our study.…”

Section: Discussionmentioning

confidence: 52%

Cytokine Profile of Engraftment Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients

Khandelwal

Mellor-Heineke

Rehman

et al. 2016

Biology of Blood and Marrow Transplantation

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The biology of engraftment syndrome is poorly understood, and the degree of overlap with acute graft-versus-host disease (GVHD) is unclear. To understand engraftment syndrome better, plasma cytokine profiles were evaluated in 56 pediatric allogeneic bone marrow transplant recipients before transplant, on the day of stem cell infusion, and weekly until day +100. Patients were divided into 4 groups: those with isolated engraftment syndrome (n = 8), acute GVHD (n = 12), both engraftment syndrome and acute GVHD (n = 4), and neither engraftment syndrome nor acute GVHD (n = 32). Engraftment syndrome was observed a median of 13.5 days (range, 10 to 28) after transplant, whereas acute GVHD was diagnosed a median of 55 days (range, 19 to 95) after transplant. Four patients developed both engraftment syndrome at a median of 10.5 days (range, 10 to 11) and acute GVHD at a median of 35 days (range, 23 to 56) after stem cell infusion. Median plasma levels of IL-1β, IL-6, IL-12, IL-4, and IL-13 were significantly elevated in patients with isolated engraftment syndrome when compared with isolated acute GVHD. A rise of proinflammatory cytokines (IL-1β, IL-6, and IL-12) was followed by surge in anti-inflammatory cytokines (IL-4 and IL-13) in patients with isolated engraftment syndrome. The observation of elevated IL-1β suggests that engraftment syndrome could be an inflammasome mediated phenomenon.

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Section: Discussionmentioning

confidence: 52%

Cytokine Profile of Engraftment Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients

Khandelwal

Mellor-Heineke

Rehman

et al. 2016

Biology of Blood and Marrow Transplantation

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“…37 However, we found no correlation between the P2X7R polymorphism and GVHD. IL-1 and IL-1Ra might be affected by P2X7R status, but the P2X7R polymorphism alone was not found to be associated with the occurrence of GVHD in the present study.…”

contrasting

confidence: 67%

P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

Lee¹,

Park²,

Kim³

et al. 2007

Haematologica

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“…In the context of alloSCT, IL-18 has been investigated primarily with respect to GVHD but clinical studies were often limited by the small numbers of subjects investigated [ 27 , 28 , 29 , 30 ]. Consequently, a correlation of IL-18 with GVHD severity was found in some alloSCT studies [ 27 , 28 ] but not in others [ 29 , 30 ]. We have previously reported that elevated pre-conditioning IL-18 levels predicted worse survival due to increased NRM [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation

Radujkovic

Kordelas

Bogdanov

et al. 2020

Cancers

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Interleukin-18 (IL-18) is an immunoregulatory cytokine and a context-dependent regulator of hematopoietic stem/progenitor cell (HSPC) quiescence in murine models. In a previous study, high pre-conditioning levels of IL-18 were associated with increased non-relapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). To investigate the clinical impact of IL-18 status on hematopoietic function, the associations of pre-conditioning and day 0–3 cytokine levels with platelet and neutrophil recovery were analyzed in a training cohort of 714 allografted patients. In adjusted logistic regression analyses, both increasing pre-conditioning and day 0–3 IL-18 levels had a significantly higher adjusted odds ratio (aOR) of delayed platelet and neutrophil recovery on day +28 post-transplant (aOR per two-fold increase: 1.6–2.0). The adverse impact of high pre-conditioning IL-18 on day +28 platelet recovery was verified in an independent cohort of 673 allografted patients (aOR per two-fold increase: 1.8 and 1.7 for total and free IL-18, respectively). In both cohorts, a platelet count ≤20/nL on day +28 was associated with a significantly increased hazard of NRM (hazard ratio 2.13 and 2.94, respectively). Our findings support the hypothesis that elevated peritransplant IL-18 levels affect post-transplant HSPC function and may provide a rationale to explore modulation of IL-18 for improving alloSCT outcomes.

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Increase of interleukin-18 serum levels after engraftment correlates with acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation

Abstract: The time course of IL-18 serum levels might be used for GvHD prediction after PBSCT comparable to absolute serum levels after BMT.

Cited by 15 publications

References 29 publications

Cytokine Profile of Engraftment Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients

Cytokine Profile of Engraftment Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients

P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation

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