Lipid Levels Increase to the Normal Range After Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease

Abstract

Individuals with sickle cell disease (SCD) have a unique type of dyslipidemia characterized by low total cholesterol (TC), low low-density lipoprotein cholesterol (LDL-c), low high-density lipoprotein cholesterol (HDL-c), and normal triglycerides (TG). This lipid state is theorized to be cardioprotective against atherosclerosis. In SCD, hematopoietic cell transplant (HCT) offers a potentially curative therapy. Long-term survivors of HCT for hematologic malignancies are at increased risk for dyslipidemia and atherosclerosis long-term. The effects of HCT on SCD dyslipidemia are unknown. This retrospective cohort study characterizes lipid profiles at baseline and after nonmyeloablative allogeneic HCT for SCD. We analyzed data from 116 patients after nonmyeloablative HLA-matched sibling or haploidentical HCT for SCD at the NIH from 2009 to 2021. TC, HDL-c, LDL-c, and TG were collected pre-HCT, 1-year post-HCT, and annually thereafter. Data were analyzed using linear generalized estimating equation regression modeling. Successful HCT was associated with a rise in TC, LDL-c, and HDL-c and a decline in TG post-HCT. After HCT, previously low lipid levels increased to the normal range. These changes occurred within the first year of HCT and were maintained thereafter. In patients with graft failure, TC and LDL-c levels remain unchanged from their pre-HCT baseline. Sirolimus use for graft versus host disease prophylaxis was associated with higher TG levels. These findings suggest that SCD dyslipidemia resolves with reversal of the SCD phenotype. The normalization of lipid parameters suggests SCD patients are not at increased risk for atherosclerosis after successful HCT compared to their peers; further studies with longer follow-up are required.

Keywords: Dyslipidemia; Graft failure; Hematopoietic cell transplant; Non-myeloablative; Sickle cell disease; Sirolimus.

Figure 1.. Mean lipid levels and 95% confidence intervals after HCT for sickle cell disease.

Total Cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) increased, and Triglyceride (TG) decreased significantly after transplant. Lipid ranges for TC, LDL-c, HDL-c, and TG are based on the Adult Treatment Panel III classification for optimal, desirable, and/or normal lipid levels for the healthy adult population .

Figure 2.. Mean total cholesterol and low-density lipoprotein measures with 95% confidence intervals post-HCT stratified by presence or absence of graft failure.

Graft failure reverted total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) to pre-HCT baseline. N=22 for Failure at baseline counted those who ever failed; N for Failure at subsequent years counted those who contributed a yearly measurement and failed at or prior to that year’s measurement. N=94 for No-Failure at baseline counted those who never failed; N for No-Failure at subsequent years counted those who contributed a yearly measurement and had not failed by the time of the measurement.

Figure 3.. Mean high-density lipoprotein cholesterol (HDL-c) and triglyceride measures with 95% confidence intervals post-HCT stratified by the presence or absence of graft failure.

The triglyceride decreased and HDL-c increased in the post-HCT setting. These changes were unaffected by graft status. N=22 for Failure at baseline counted those who ever failed; N for Failure represented those who contributed a yearly measurement and failed at or prior to that year’s measurement. N=94 for No-Failure at baseline counted those who never failed;-N for No-Failure represented those who contributed a yearly measurement and had not failed by the time of the measurement.