Engraftment Syndrome after Allogeneic Hematopoietic Cell Transplantation Predicts Poor Outcomes
ABSTRACT 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 following 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 9-12) post-HCT. ES patients experienced significantly higher cumulative incidence of grade 2-4 acute GVHD at day 100 (75% vs. 34%, p<0.001) and higher non-relapse mortality at 2 years (38% vs. 19%, p<0.001), compared with non-ES patients, resulting in lower overall survival at 2 years (38% vs. 54%, p<0.001). There was no significant difference in relapse at 2 years (26% vs. 31%, p=0.772). ST2, IL2Rα, and TNFR1 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.
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ABSTRACT: We suggest that acute GVHD after marrow transplantation reflects (1) host injury due to the conditioning regimen followed by the production of inflammatory cytokines; (2) stimulation of mature donor T cells in the milieu of increased cell surface expression of leukocyte adhesion molecules and HLA molecules, followed by the autocrine production of IL-2; and, finally, (3) recruitment and activation of additional mononuclear effector cells from donor marrow progenitors, which produce additional inflammatory cytokines, thus sustaining the response. The second step is critical for the amplification of the systemic inflammatory response, and it is absence in autologous, syngeneic, and T-cell-depleted transplants. These T cells may also contribute to the inflammatory cytokine network. Acute GVHD can occur in the absence of primary tissue injury in such settings as transfusion-related GVHD; however, it is likely that a greater HLA disparity between donor and host is required. We propose that inflammatory cytokine production is the final common pathway of acute GVHD. If this model is correct, control of cytokine dysregulation at any of several points should control GVHD. Further studies of GVHD and investigations of cytokine antagonists (eg, IL-4 or IL-10) or combinations of antagonists such as IL-1ra and soluble TNF receptor or pentoxifylline will allow us to determine the validity of this hypothesis.Blood 01/1993; 80(12):2964-8. · 9.78 Impact Factor
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ABSTRACT: From 1987 to 1998, 19 of 416 patients (4.6%) who underwent autologous hematopoietic stem cell transplantation experienced peri-engraftment (within 5 days of neutrophil recovery) respiratory distress syndrome (PERDS) not attributable to infection, fluid overload, or cardiac dysfunction. The median time from stem cell infusion to onset of PERDS was 11 days (range 4-25). Risk of PERDS or its outcome was not predicted by any pre- or peri-transplant clinical or laboratory feature. The respective median white blood cell and platelet counts at first symptoms were 1.3 x 10(9)/l and 25 x 10(9)/l. No patients had an infectious etiology by bronchoalveolar lavage. Six of the 19 patients had alveolar hemorrhage, which was significantly correlated with high neutrophil count. PERDS was directly implicated in four deaths (21%). Eleven patients received high-dose corticosteroid therapy, including five of the six who required mechanical ventilation. Ten of these patients experienced clinical improvement, which occurred within 24 h in five. The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit.Bone Marrow Transplantation 07/2001; 27(12):1299-303. DOI:10.1038/sj.bmt.1703075 · 3.47 Impact Factor
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ABSTRACT: Pre-engraftment syndrome (PES) occurring after cord blood transplantation (CBT) is poorly characterized. We reviewed 52 consecutive double-unit CBT recipients treated for high-risk hematologic malignancies. PES was defined as unexplained fever >38.3 degrees C (101 degrees F) not associated with infection and unresponsive to antimicrobials, and/or unexplained rash occurring before or at neutrophil recovery. CBT recipients (median age, 38 years; range, 3-66 years) received either myeloablative (MA; n=36) or nonmyeloablative (NMA; n=16) conditioning. Sixteen patients (31%) fulfilled PES criteria: 15 with fever (median at onset, 39 degrees C [102.2 degrees F]), 13 of whom also had rash, and 1 with rash alone. The median onset was 9 days (range, 5-12 days) posttransplantation (a median of 14 days before neutrophil recovery). Sixteen patients (14 with PES and 2 with infection and possible PES) received intravenous methylprednisolone (median dose, 1mg/kg; median duration, 3 days); 15 (94%) experienced resolution of fever within 24 hours. Recurrent PES (n=3) resolved with retreatment. There was no association between the development of PES and the likelihood of sustained donor engraftment, speed of neutrophil recovery, grade II-IV acute graft-versus-host disease (aGVHD), day-180 treatment-related mortality (TRM), or survival. PES is common after CBT, precedes neutrophil recovery, is distinct from and does not predict for aGVHD, and responds promptly to short-course corticosteroid therapy.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2009; 16(3):435-40. DOI:10.1016/j.bbmt.2009.10.022 · 3.15 Impact Factor