Effects of short-term pretreatment with atorvastatin on mobilization of hematopoietic progenitor cells: A double-blind, randomized, controlled trial
Background: Despite recent advances in mobilization techniques, a considerable portion of patients fail to mobilize sufficient number of cells for successful autologous stem cell transplantation. There are several studies available that have demonstrated enhanced mobilization of endothelial progenitor cells with atorvastatin. Therefore, this prospective trial was conducted to evaluate the mobilizing effect of atorvastatin on hematopoietic progenitor cells.
Subjects and Methods: Forty-four autologous HSCT candidates were randomized in a double-blind controlled trial to receive atorvastatin 40 mg daily or placebo plus standard G-CSF regimen. Treatment was initiated at the time of hospitalization and continued until the day of cell harvest. Independent-samples T-Test, Repeated Measures ANOVA and Mann-Whitney U test were performed to compare means. Categorical variables were analyzed using Chi-square and Fisher’s exact test.
Results: Mean number of hematopoietic progenitor cells per microL of peripheral blood at the time of cell harvest did not differ significantly between the two groups. There was no statistically significant difference in secondary outcomes like time of platelet or PMN engraftment, occurrence of bleeding or infectious episode, duration of hospitalization and etc.
Conclusion: The results of this study did not support beneficial effects of atorvastatin on mobilization of hematopoietic progenitor cells from bone marrow.
Passweg JR, Baldomero H, Peters C, et al. Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation. Bone marrow transplantation. 2014 Jun; 49(6):744-50.
Hamadani M. Autologous hematopoietic cell transplantation: An update for clinicians. Ann Med. 2014 Sep 11: 1-14.
Moog R. Management strategies for poor peripheral blood stem cell mobilization. Transfusion and apheresis science: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis. 2008 Jun; 38(3):229-36.
Nagler A, Labopin M, Shimoni A, et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012 Sep; 18(9):1422-9.
Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012 Oct 18; 367(16):1487-96.
Powles R, Mehta J, Kulkarni S, et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial. Lancet. 2000 Apr 8; 355(9211):1231-7.
Bakanay SM, Demirer T. Novel agents and approaches for stem cell mobilization in normal donors and patients. Bone marrow transplantation. 2012 Sep; 47(9):1154-63.
Giralt S, Costa L, Schriber J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation. 2014 Mar; 20(3):295-308.
Ozkurt ZN, Yegin ZA, Suyani E, et al. Factors affecting stem cell mobilization for autologous hematopoietic stem cell transplantation. J clin Apher. 2010; 25(5):280-6.
Pusic I, DiPersio JF. Update on clinical experience with AMD3100, an SDF-1/CXCL12-CXCR4 inhibitor, in mobilization of hematopoietic stem and progenitor cells. Curr opin hematol. 2010 Jul; 17(4):319-26.
Lor KW, Helmons PJ, Belew H, et al. Plerixafor as first- and second-line strategies for autologous stem cell mobilization in patients with non-Hodgkin's lymphoma or multiple myeloma. Pharmacotherapy. 2012 Jul; 32(7):596-603.
Perkins JB, Shapiro JF, Bookout RN, et al. Retrospective comparison of filgrastim plus plerixafor to other regimens for remobilization after primary mobilization failure: clinical and economic outcomes. Am J Hematol. 2012 Jul; 87(7):673-7.
Hibbert B, Simard T, Ramirez FD, et al. The effect of statins on circulating endothelial progenitor cells in humans: a systematic review. Journal of cardiovascular pharmacology. 2013 Nov; 62(5):491-6.
Zhou J, Cheng M, Liao YH, et al. Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells. Plos one. 2013; 8(5):e63126.
Steinmetz M, Pelster B, Lucanus E, et al. Atorvastatin-induced increase in progenitor cell levels is rather caused by enhanced receptor activator of NF-kappaB ligand (RANKL) cell proliferation than by bone marrow mobilization. J Mol Cell Cardiol. 2013 Apr; 57:32-42.
Stravodimou A, Voutsadakis IA. Statin use and peripheral blood progenitor cells mobilization in patients with multiple myeloma. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2014 Jan; 16(1):85-90.
Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006 Feb 16; 354(7):731-9.
Rosenson RS, Baker SK, Jacobson TA, et al. The National Lipid Association's Muscle Safety Expert P. An assessment by the Statin Muscle Safety Task Force: 2014 update. Journal of clinical lipidology. 2014 May-Jun; 8(3 Suppl):S58-71.
Cogle CR, Wainman DA, Jorgensen ML, et al. Adult human hematopoietic cells provide functional hemangioblast activity. Blood. 2004 Jan 1; 103(1):133-5.
Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke; a journal of cerebral circulation. 2008 Jan; 39(1):69-74.
Prunier F, Pfister O, Hadri L, et al. Delayed erythropoietin therapy reduces post-MI cardiac remodeling only at a dose that mobilizes endothelial progenitor cells. Am Journal Physiol Heart circ Physiol. 2007 Jan; 292(1):H522-9.
To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011 Oct 27; 118(17):4530-40.
Hibbert B, Ma X, Pourdjabbar A, et al. Pre-procedural atorvastatin mobilizes endothelial progenitor cells: clues to the salutary effects of statins on healing of stented human arteries. Plos one. 2011; 6(1):e16413.
Leone AM, Rutella S, Giannico MB, et al. Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial. Int J cardiol. 2008 Nov 28; 130(3):457-62.
Jaumdally RJ, Goon PK, Varma C, et al. Effects of atorvastatin on circulating CD34+/CD133+/ CD45- progenitor cells and indices of angiogenesis (vascular endothelial growth factor and the angiopoietins 1 and 2) in atherosclerotic vascular disease and diabetes mellitus. J Intern Med. 2010 Apr; 267(4):385-93.
Hristov M, Fach C, Becker C, et al. Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment. Atherosclerosis. 2007 Jun; 192(2):413-20.
Baran C, Durdu S, Dalva K, et al. Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial. Stem cell reviews. 2012 Sep; 8(3):963-71.
Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation. 2001 Jun 19; 103(24):2885-90.
Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends in molecular medicine. 2008 Jan; 14(1):37-44.
Timmermans F, Plum J, Yoder MC, et al. Endothelial progenitor cells: identity defined? J cell mol Med. 2009 Jan; 13(1):87-102.
|Issue||Vol 9, No 4 (2015)|
|Atorvastatin Autologous HSCT Mobilization|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|