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Predictive value of the proliferation marker Ki-67 in patients with acute leukemia undergoing hematopoietic stem cell transplantation

Introduction Hematopoietic stem cell transplantation (HSCT) is increasingly used in cases of acute leukemia. Ki-67 protein is an excellent marker of proliferation in many solid tumors and hematological malignancies. Aim The aim was to evaluate the utility of Ki-67 as a prognostic marker before HSCT. Patients and methods The study included 40 adult Egyptian patients with acute leukemia undergoing HSCT. Plasma Ki-67 levels were measured by enzyme-linked immunosorbent assay before transplant and after (at the date of engraftment or day 30 if engraftment failure occurred). Results The median levels and (range) of plasma Ki-67 before and after transplant were 1.85±5.48 and 1.19±3.22 ng/ml, respectively. We found higher plasma Ki-67 levels (before and after transplant were correlated with more delayed engraftment (r=0.425,P=0.007 before transplant; r= 0.361 P=0.024 after transplant), and more prolonged neutropenic fever duration (r=0.377, P=0.017 before transplant; r=0.387, P=0.014 after transplant). Patients having acute graft-versus-host disease (GVHD) during the first month of HSCT also had higher levels of plasma Ki-67 before and after HSCT compared with patients who did not develop acute GVHD, with median (range) of 15.85 (0.20-27.40) ng/ml vs 0.30 (0.10-1.70) ng/ml (P=0.029) before transplant and 6.15 (3.90-18.90) ng/ml vs 0.20 (0.10-2.80) ng/ml (P= 0.001) after transplant. Plasma Ki-67 levels of greater than or equal to 6.4 ng/ml before transplantation (75% sensitivity and 100% specificity) and greater than or equal to 3.35 ng/ml after transplantation (100% sensitivity and specificity) are predictive values for detection of occurrence of acute GVHD. Conclusion High levels of plasma Ki-67 in patients with acute leukemia undergoing HSCT may be a predictor of delayed engraftment, prolonged neutropenic fever and occurrence of acute GVHD.