Diagnosis of Light Chain Amyloidosis Is the Primary Risk Factor for Engraftment Syndrome after Autologous Stem Cell Transplant in a Contemporary Cohort

Abstract

Engraftment syndrome (ES) after autologous stem cell transplant (ASCT) is characterized by non-infectious fevers, skin rash, hypoxia, acute kidney injury (AKI) among other signs and is defined by the Spitzer or Maiolino criteria. It is a significant cause of morbidity and rarely mortality; risk factors and etiology are poorly understood. We sought to perform an analysis of risk factors and outcomes in patients with ES in a contemporary cohort. We performed a retrospective analysis of consecutive patients with lymphoma or plasma cell dyscrasia who received their first ASCT between 01/2012 and 06/2018. ES was defined according to the Spitzer criteria. Chi-square or Fisher's exact test is used to compare categorical variables and t-test is used for continuous variables. Logistic regression was performed for binary outcomes. Kaplan Meier estimator and cox model were used to explore associations between predictors and time-to-event outcomes. Stepwise regression was used for variable selection. We included 188 patients in this analysis. Median follow up was 28 months. Leading primary diagnosis was myeloma (n=73, 38.3%), followed by NHL (n=53, 28.2%), Amyloidosis (n=31, 16.5%), Hodgkin lymphoma (n=24, 12.8%), and POEMS (n=5, 2.7%). Seventeen patients developed ES (n=17, 9.0%) and 13 patients were treated with corticosteroids. Complete resolution was seen in 16 patients, 1 patient with ES died shortly after engraftment. Two patients treated with corticosteroids had relapse of ES and required a second course of corticosteroids, one of whom required a third course. ES was associated with the primary diagnosis (p=0.0014) and age (p=0.033) but was not associated with gender (p=0.20), use of plerixafor (p=0.68), TNC cell dose (p=0.82), CD34 cell dose (p=0.66), and graft volume (p=0.91). Patients with ES had a higher rate of steady state mobilization which approached significance (94.1% vs 74.3%, p=0.053). Logistic regression analysis confirmed diagnosis of amyloidosis as the primary risk factor for ES (OR of 7.62, p=0.0002). ES had no impact on OS (p=0.91, fig 1) or PFS (p=0.79, fig 2). 1-year survival rate was 98.1% in patients without ES and 94.1% in patients with ES whereas 1-year PFS rates were 87.1% and 78.1% respectively according to Kaplan Meier estimates. ES remains common in a contemporary cohort of ASCT recipients. Use of plerixafor, which has been increasingly common, did not impact incidence. Primary diagnosis of amyloidosis was the most important risk factor. While one mortality was attributed to ES, ES had no impact on OS or PFS in the overall cohort.