Hyperlipidemia After Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Blaser Bradley W , Kim Haesook , Plutzky Jorge , Alyea Edwin , Ho Vincent , Cutler Corey , Armand Philippe , Koreth John , Antin Joseph H. , Soiffer Robert 
Published: October 2019

Abstract
Abstract 3457
An increased incidence of cardiovascular complications has been documented in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several cross-sectional retrospective studies have described the incidence of cardiovascular risk factors such as lipid elevation late after allo-HSCT, but none have yet considered changes in cholesterol and triglyceride levels within the first two years. We performed a retrospective analysis of all patients who underwent allo-HSCT at the Dana-Farber Cancer Institute from 1998 to 2008 and who survived more than 100 days. Of these, 761 had at least one measurement of total cholesterol or triglyceride level from day 30 to 2 years following transplantation. The decision to check lipid levels was made at the discretion of the outpatient physician. Among the patients with measured cholesterol or triglyceride levels, median age at transplantation was 49 (range 17–73), 58% received grafts from unrelated donors, and 55% received myeloablative conditioning. Greater than 95% of patients received tacrolimus based GVHD prophylaxis. Sirolimus was part of GVHD prophylaxis for 50%. The cumulative incidence of grades 2–4 acute GVHD was 27%. Seventy-three percent of patients were hypercholesterolemic (total cholesterol >=200 mg/dL) and 87% were hypertriglyceridemic (triglycerides >=150 mg/dL) within the study time period post-transplantation. In contrast, only 32% of patients were hypercholesterolemic and 59% were hypertriglyceridemic in the ninety days prior to transplantation. Median time to detection of first elevated total cholesterol and triglycerides was 116 and 108 days after transplantation, respectively. Among all patients, median change between peak pre- and post-transplantation levels was 62 mg/dL for total cholesterol and 109 mg/dL for triglycerides. Median peak total cholesterol and triglyceride levels after transplantation were 241 mg/dL and 275 mg/dL, respectively. In univariable analysis (see Table), myeloablative conditioning, age, or diagnosis did not affect development of hypercholesterolemia or hypertriglyceridemia. However, sirolimus prophylaxis did correlate with hypertriglyceridemia (OR 1.91, 95% CI 1.23–2.95, P = 0.004), but not hypercholesterolemia (OR 1.21 95% CI 0.87–1.67). The development of grade 2–4 acute GVHD was associated with both hypercholesterolemia (OR 1.7 95% CI 1.2–2.6, P = 0.007) and hypertriglyceridemia (OR 2.2 95% CI 1.2–3.9, P = 0.007). A search of the outpatient prescription records of all 761 patients with lipid measurements revealed that HMG-CoA reductase inhibitors (statins) were prescribed for 35% of patients after transplantation. These data are the first to document the incidence of hyperlipidemia in the first two years after allo-transplantation when most patients remain under the care of the transplantation physician and lipid-lowering therapy may be under-utilized. Hyperlipidemia is common in these patients, particularly in those with acute GVHD. Whether the hyperlipidemia observed early after transplantation is associated with adverse cardiovascular events is currently under investigation. Given the cardiovascular risk associated with hyperlipidemia, the tolerability of statins, and the suggestion that statins may have favorable immunomodulatory effects as seen in solid organ transplantation, further prospective evaluation of lipid abnormalities and their treatment seems well warranted.
Table 1. Univariable Analysis of Risk Factors for Post-Transplantation Hyperlipidemia Cholesterol >=200 mg/dL Triglyceride >= 150 mg/dL OR 95% CI P OR 95% CI P Age >= 50 1.29 0.93 – 1.79 0.12 0.85 0.55 – 1.30 0.45 Myeloid neoplasm 0.97 0.70 – 1.35 0.84 1.10 0.71 – 1.70 0.66 Sirolimus prophylaxis 1.21 0.87 – 1.67 0.25 1.91 1.23 – 2.95 0.004 Myeloablative conditioning 0.94 0.68 – 1.29 0.68 1.05 0.68 – 1.62 0.81 Grade 2–4 acute GVHD 1.7 1.2 – 2.6 0.007 2.2 1.2 – 3.9 0.007

Disclosures:
No relevant conflicts of interest to declare.