Possible Predictors of Poor Angiogenesis after Hematopoietic Stem Cell Autograft for Lower Limb Ischemia

INTRODUCTION The therapeutic potential of adult stem cells in coronary and peripheral arterial diseases has been proposed in recent years. However, factors possibly predictive of unfavorable angiogenic results have not been clearly identified as yet. OBJECTIVES Identify candidate predictors of poor angiogenesis, as indicated by need for amputation, after autologous hematopoietic stem cell transplantation for chronic lower limb ischemia. METHODS A retrospective analytical case-series study was carried out to detect factors possibly associated with hematopoietic stem cell autograft failure due to low angiogenic potential. The study universe was composed of 47 patients (19 women, 28 men) with critical lower limb ischemia in Fontaine stages IIb, III and IV, who received autologous stem cell transplantation at the Dr Gustavo Aldereguia Lima University General Hospital in Cienfuegos, Cuba, from January 2007 through December 2010. Variables studied were sex, age, medical history (high blood pressure, ischemic cardiomyopathy, diabetes mellitus and chronic renal insufficiency), Fontaine ischemia stage, intermittent claudication, pain score on a 1-10 scale, ankle-brachial pressure index in the affected extremity, presence of ulcers, and smoking. Laboratory variables included: blood concentrations of hemoglobin, glucose, creatinine, liver enzymes, cholesterol, triglycerides and LDH; as well as leukocyte and platelet counts, stem cell viability, prothrombin time and erythrocyte sedimentation rate. The main response variable was amputation, an indicator of poor angiogenesis. Using logistic regression, a prognostic score of 1 to 4 was developed for each risk factor and scores added to create a risk prediction scale. Predicted risk for amputation and observed amputation rates were compared for patients in three risk groups: low, 0-4; medium, 5-8; and high, 9-12. RESULTS Factors identified as possibly predictive of poor angiogenesis were: final leukocyte count <20 x 10(9)/L after mobilization with granulocyte colony stimulating factor; age >= 60 years; pain scale score of 10; glycemia of >6 mmol/L; and triglycerides of >1.8 mmol/L. Patients who scored low on predicted amputation risk scale were spared amputation in 90.9% (10/11) of cases, versus 16.7% (2/12) in patients scoring high. CONCLUSIONS Five possible prognostic factors for low angiogenic potential in stem cell autotransplantation were identified and a preliminary scale established to predict in which patients autotransplantation would be more likely to be successful.