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. 2014 Sep;20(9):1407-17.
doi: 10.1016/j.bbmt.2014.05.022. Epub 2014 Jun 2.

Engraftment Syndrome After Allogeneic Hematopoietic Cell Transplantation Predicts Poor Outcomes

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Engraftment Syndrome After Allogeneic Hematopoietic Cell Transplantation Predicts Poor Outcomes

Lawrence Chang et al. Biol Blood Marrow Transplant. .
Free PMC article


Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES patients, resulting in lower overall survival at 2 years (38% versus 54%, P < .001). There was no significant difference in relapse at 2 years (26% versus 31%, P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and tumor necrosis factor receptor 1 plasma biomarker levels were significantly elevated in ES patients. Our results illustrate the clinical significance and prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES.

Keywords: Cytokine storm; Engraftment syndrome; Hematopoietic cell transplantation.


Figure 1
Figure 1. Distribution of study patients and outcomes
Steroids refer to engraftment syndrome (ES) treatment with systemic corticosteroids. Hematopoietic cell transplantation (HCT) *Graft-versus-host disease (GVHD) refers to maximum acute GVHD grade † ES includes patients who met only 2 Major Spitzer criteria but no minors, yet were advanced on systemic steroids in addition to those who also fulfilled the Spitzer criteria of 3 Majors or 2 Majors plus1 Minor criteria—all without the 96 hour time criterion for these signs and symptoms.
Figure 2
Figure 2. Biomarker Studies
Shown are (▪) ES versus formula image No ES. Day 0 and day 14 mean change in plasma levels of (A) suppression of tumorigenicity 2 (ST2), (▪) n= 43, formula image n= 252; (B) interleukin 2 receptor α (IL2Rα), (▪) n= 64, formula image n= 165; (C) tumor necrosis factor receptor 1 (TNFR1), (▪) n= 64, formula image n= 165.
Figure 3
Figure 3. Steroid Data
Median methylprednisolone equivalent dosing course over time dichotomized by baseline starting dose of ≥1.5 mg/kg/day (solid) and < 1.5 mg/kg/d (dashed) at onset of engraftment syndrome (ES). The corresponding table shows hazard ratios of clinical outcomes comparing this baseline dichotomy.
Figure 4
Figure 4. Clinical outcomes for engraftment syndrome (ES) and non-ES patients
Cumulative incidence of (A) Acute GVHD Grades 2–4, (B) Overall survival, (C) Relapse, and (D) Non-relapse mortality.

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