TY - JOUR
T1 - Elevated activated partial thromboplastin time during administration of first-generation adenoviral vectors for gene therapy for prostate cancer
T2 - Identification of lupus anticoagulants
AU - Malaeb, Bahaa S.
AU - Gardner, Thomas A.
AU - Margulis, Vitaly
AU - Yang, Ling
AU - Gillenwater, Jay Y.
AU - Chung, Leland W K
AU - Macik, Gail
AU - Koeneman, Kenneth S.
N1 - Funding Information:
This work was supported by a New Award Idea, Department of Defense, CDMRP, DAMD 17-01-1-0107 “Targeting Osteoblastic Bone Metastasis with a Novel Site Restricted Gene Therapy” and Department of Defense, CDMRP, DAMD17-02-1-0148 “Targeting Orthotopic and Osseous Prostate Cancer Xenografts with Selective, Systemic Telomerase Inhibition” to Dr. Koeneman, and a subcontract to DOD Consortium Award, DAMD17-03-2-0033 to Emory University (P.I. Jonathan Simmons).
PY - 2005/10
Y1 - 2005/10
N2 - Objectives. To evaluate the cause and significance of elevated activated partial thromboplastin time (aPTT) in a group of patients who received a first-generation adenoviral vector (Ad-OC-TK) delivering a toxic gene to prostate cancer cells as part of a Phase I clinical trial at the University of Virginia. Methods. Eleven subjects were injected intratumorally to metastatic lesions of prostate cancer in the prostatic fossa, retroperitoneal lymph nodes, or bone (iliac, ischium, or vertebrae). After the initial laboratory evaluation, patients with elevated aPTT underwent a series of additional tests, including mixing studies, coagulation factor, prekallikrein, and high-molecular-weight kininogen, and lupus anticoagulant studies (modified Russell viper venom time) with phospholipid correction, and a Staclot LA assay. Results. Of the 11 subjects who were enrolled in the trial, 6 had elevated aPTT values. Of the 6 patients, 3 had aPTT elevation of more than 10 seconds above normal. Two of the subjects with higher values demonstrated an inhibitory pattern with the factor VIII and XI assays, and the lupus anticoagulant studies were positive. No clinical sequelae to the elevated aPTT values were observed. Conclusions. This is, to our knowledge, the first formal report of a first-generation adenoviral vector causing a slight transient elevation of the aPTT through the induction of an antiphospholipid antibody. No clinical sequelae related to elevated aPTT values were observed. The adenoviral protocol was safe; similar protocols should be aware of this phenomenon.
AB - Objectives. To evaluate the cause and significance of elevated activated partial thromboplastin time (aPTT) in a group of patients who received a first-generation adenoviral vector (Ad-OC-TK) delivering a toxic gene to prostate cancer cells as part of a Phase I clinical trial at the University of Virginia. Methods. Eleven subjects were injected intratumorally to metastatic lesions of prostate cancer in the prostatic fossa, retroperitoneal lymph nodes, or bone (iliac, ischium, or vertebrae). After the initial laboratory evaluation, patients with elevated aPTT underwent a series of additional tests, including mixing studies, coagulation factor, prekallikrein, and high-molecular-weight kininogen, and lupus anticoagulant studies (modified Russell viper venom time) with phospholipid correction, and a Staclot LA assay. Results. Of the 11 subjects who were enrolled in the trial, 6 had elevated aPTT values. Of the 6 patients, 3 had aPTT elevation of more than 10 seconds above normal. Two of the subjects with higher values demonstrated an inhibitory pattern with the factor VIII and XI assays, and the lupus anticoagulant studies were positive. No clinical sequelae to the elevated aPTT values were observed. Conclusions. This is, to our knowledge, the first formal report of a first-generation adenoviral vector causing a slight transient elevation of the aPTT through the induction of an antiphospholipid antibody. No clinical sequelae related to elevated aPTT values were observed. The adenoviral protocol was safe; similar protocols should be aware of this phenomenon.
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U2 - 10.1016/j.urology.2005.04.041
DO - 10.1016/j.urology.2005.04.041
M3 - Article
C2 - 16230147
AN - SCOPUS:26644466325
SN - 0090-4295
VL - 66
SP - 830
EP - 834
JO - Urology
JF - Urology
IS - 4
ER -