Post Autologous Stem Cell Transplantation (ASCT) Engraftment Syndrome: Improved Treatment and Outcomes

Abstract

Post ASCT engraftment syndrome (ES) is a well-known clinical complication, however many aspects of its etiology, treatment and outcomes remain largely controversial. In this retrospective study, we hypothesized that ES is frequent, and empiric treatment of presumed ES with steroids improves patient outcomes. We reviewed records of 138 ASCTs done over recent 18 months in our institution and identified patients with the diagnosis of ES. ES was defined as fever and/or skin rash and/or diarrhea and/or pulmonary manifestations that started around the engraftment day and in the absence of evidence for infection. Our results show that 39 patients (28.3%) were diagnosed with ES, with incidence of 32.6% in multiple myeloma/amyloidosis versus 23.8% in lymphoma and other diseases. We used SPSS v25 for statistical analysis and present P values for 2-tailed t-test or Fisher's exact test. Compared to patients without ES, patients with ES were significantly more likely to have fever, skin rash, diarrhea, and higher LDH levels on first day of engraftment. Risk factors for ES included shorter time from diagnosis to ASCT (P=0.038), older age (P=0.04), higher CD34+ cell dose (P=0.02) which caused less use of post ASCT G-CSF, and lower absolute lymphocyte count on first engraftment day (P=0.04). All ES patients received treatment with steroids. Initial dose of prednisone/methylprednisolone was 2 mg/kg (n=31), 1 mg/kg (n=5), while 3 patients received 1000 mg as the starting dose. The median length of steroid therapy was 7.5 days (range, 3-19). One ES patient with bad diarrhea died of cardiac arrest who received only 3 days of lower dose steroids, and another ES patient intubated for respiratory failure who had full recovery with delayed start of steroids treatment. Only one ES patient had documented bacteremia with fever spike. In conclusion, our study suggests that fever, even without rash, around the time of engraftment is likely to be ES related and not infection. Overall survival of ES patients has improved with greater awareness of the diagnosis and earlier use of steroids.