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

Abstract

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.

Incorporating Inflammation into Mortality Risk in Pediatric Acute Respiratory Distress Syndrome

“…Recent data suggest that HCT patients may have unique inflammatory derangements after transplantation that might differentiate mortality risk (43, 44). Clinical experience with pulmonary dysfunction during neutrophil engraftment as well as early success of TNF-α inhibition support the exaggerated role of inflammation in this population (45, 46). Although our ability to draw further conclusions was limited by the size of this subgroup, this analysis is an important first step in identifying clinically-validated molecular markers that differentiate subgroups of risk.…”

Impaired immune function in children and adults with Fanconi anemia

“…Plasma cytokines were analyzed using the Human Cytokine Magnetic 10‐plex Panel from Life Technologies as previously published . In short, this panel measures the plasma concentration of the following cytokines: interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, GM‐CSF, IFN‐γ, and TNF‐α using beads of defined spectral properties conjugated to analyte‐specific capture antibodies.…”

Engraftment Syndrome: An Updated Review

“…Chest radiography may show: interstitial pulmonary edema, pulmonary infiltrates that may be diffuse, and pleural effusions [11,32]. Recently described findings that may serve as biomarkers of ES include: (1) elevated serum procalcitonin level, (2) expression of elafin, a protein secreted in response to IL-1 or TNF-α, in the peripheral blood or elevated blood level of elafin, (3) elevated proinflammatory cytokines such as IL-1β, IL-6 and IL-12 followed by a surge in anti-inflammatory cytokines including: IL-4 and IL-13, in addition to (4) elevated CRP [1,11,33,34].…”