Hypercholesterolemia and its association with enhanced stem cell mobilization and harvest after high-dose cyclophosphamide+G-CSF

Abstract

High-dose chemotherapy with autologous peripheral blood SCT is a common treatment option in several hematological and non-hematological malignancies. So far, prediction of successful stem cell mobilization and harvest is limited. Just recently, hypercholesterolemia was shown to increase mobilization of hematopoietic progenitor cells into the peripheral circulation in mice. On the basis of these results, we performed a retrospective multivariate analysis incorporating a variety of clinical parameters in 83 patients following high-dose cyclophosphamide þ G-CSF treatment. Interestingly, we found a significant positive correlation between stem cell mobilization and harvest for plasma cholesterol and lactate dehydrogenase (LDH) only. Patients with hypercholesterolemia showed a substantially higher median peripheral blood CD34 þ -peak (126 vs 47/lL, P ¼ 0.003), higher median number of harvested CD34 þ -cells/kg (9.6 vs 7.4 Â 10 6 /kg, Po0.001) and a sufficient number for at least one SCT in a remarkably higher proportion (84.9 vs 52.9%, P ¼ 0.003) compared with patients with normal cholesterol levels.

Higher BMI is not a barrier to stem cell mobilization with standard doses of plerixafor and G-CSF

“…[3][4][5] Moreover, hypercholesterolemia, which frequently accompanies increased BMI, seems to promote stem-cell mobilization, and this was documented in both an experimental murine model, and a retrospective analysis of clinical data. 6,7 High cholesterol levels may interfere with the SDF-1/CXCR4 axis by induction of a proinflammatory state, activation of complement the cascade and an increase in serum SDF-1. Plerixafor is a new agent used in combination with G-CSF in myeloma and lymphoma patients, who failed a previous mobilization attempt.…”

27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy

“…Nonetheless, it is possible that in addition to regulating ERα function, 27HC also influences HSCs through effects on bile acid biosynthesis. Our results offer a potential explanation for the long-standing observation that increased cholesterol levels are associated with increased HSPC mobilization in mice and humans (11)(12)(13)(14)(15)(16). 27HC levels increase as cholesterol levels increase (6).…”

“…Several studies have reported a correlation between cholesterol levels and HSPC numbers in human blood (34). Patients with hypercholesterolemia mobilize larger numbers of CD34 + HSPCs following treatment with cyclophosphamide and G-CSF as compared with patients with lower cholesterol levels (14). Moreover, plasma cholesterol levels increase in humans during pregnancy (35).…”

“…Nonetheless, cholesterol is known to promote HSC proliferation and mobilization (11)(12)(13). Patients with hypercholesterolemia mobilize larger numbers of CD34 + cells following treatment with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) as compared with patients with lower cholesterol levels (14). Mice with defects in cholesterol efflux as a result of Abca1 and Abcg1 transporter deficiency display increased hematopoietic stem and progenitor cell (HSPC) numbers, proliferation, and mobilization (15,16).…”

The impact of diabetes mellitus and other comorbidities on hematopoietic stem cell collection and hematologic recovery post-transplantation

“…[3] In our study, patients were classified by clinical diagnosis, not confirmed by laboratory values. This allowed us to examine the impact of hyperlipidemia and its long-term sequelae on mobilization but did not, if the patient is appropriately treated, allow us to examine the impact of elevated blood lipids.…”