Engraftment syndrome after allogeneic hematopoietic cell transplantation in adults

Abstract

We performed a retrospective study of the engraftment syndrome (ES) as defined by the Spitzer Criteria in adult patients undergoing allogeneic hematopoietic cell transplantation (HCT) for various hematological malignancies at a single institution, over a decade, and analyzed its relationship to acute GVHD; 217 patients underwent either myeloablative (38.7%) or reduced intensity (61.3%) HCT; 22.1% met the criteria for ES. Acute GVHD prophylaxis (P 5 0.006) and transplants prior to 2006 (P < 0.0001) were significantly associated with a risk of ES in univariable analysis. Early aGVHD within 4 weeks of engraftment was significantly more common in the ES compared to the non ES cohort (21 vs. 8.3% respectively, P 5 0.02). ES did not predict for future GVHD, as at day 1180, the cumulative incidences of grades II-IV aGVHD (31 vs. 23%, P 5 0.19) and of chronic GVHD at 2 years of engraftment (42 vs. 36%, P 5 0.28) were not significantly different between the ES and non ES groups, respectively. No significant differences in NRM, overall survival and progression-free survival were observed between the two groups. Although predictive of early aGVHD, ES occurred independently of GVHD in 79% of the patients. Survival outcomes should be evaluated in a larger randomized study to investigate if there is a correlation with ES.

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

“…We recently reported a 22% incidence of ES among 217 adult allotransplant recipients with diverse hematological neoplasms and other blood disorders. 11 There was a strong association between ES and onset of acute GVHD before day 28. The cumulative incidences of acute and chronic GVHD, however, were not increased in subjects with ES.…”

“…11 Indications for treatment include a temperature of 439°C without an identifiable infectious etiology and clinically significant manifestations of vascular leak, especially pulmonary edema. ES is very corticosteroid responsive and treatment is given only as long as symptoms persist, usually o1 week.…”

“…Although GVHD may be more common in persons with ES, ES as a self-limited syndrome or one that resolves after a short course of treatment without the developement of acute GVHD has been well described. [9][10][11] ES is also reported after autotransplants seemingly excluding GVHD in some instances. There are also conflicting data regarding an association between ES, NRM and survival.…”

“…There are also conflicting data regarding an association between ES, NRM and survival. 1,2,[10][11][12][13][14][15] Some of these discordances likely reflect different definitions of ES.…”

Non-Infectious Early Complications of Allogeneic Stem Cell Transplantations

“…60 The incidence of ES is varying from 5% to 72% because the definition and criteria of ES are not described precisely. 60 Diagnostic definition suggested by Spitzer contains major and minor criteria: a temperature of ≥ 38 0 C without a defined infectious etiology, erythrodermic rashes not related to any drug covering a body area over 25%, non-cardiogenic pulmonary edema accompanying with hypoxia and diffuse pulmonary infiltrates are major criteria, hepatic dysfunction with either bilirubin of ≥ 2 mg/ dL or transaminase levels of ≥ 2 times normal, renal failure, weight gain of ≥ 2.5% of baseline body weight and a transient encephalopathy unexplained by other causes are considered as minor criteria. 61 For diagnosis, all three major criteria or two major criteria and one or more minor criteria, within 96 hours of engraftment is sufficient.…”