A Medical Device Daily Staff Report

The Ohio State University (Columbus, Ohio), a clinical development partner of diagnostic company Ciphergen Biosystems (Fremont, California), presented data demonstrating the clinical utility of its assay to manage patients with thrombotic thrombocytopenic purpura (TTP) at the 48^th meeting of the American Society of Hematology (ASH; Washington) in Orlando, Florida, that concludes today.

TTP is a disorder characterized by low platelets, low red blood cell count (caused by premature breakdown of the cells), neurological abnormalities and sometimes abnormalities in kidney function. In most cases, this disease is caused by a deficiency in or auto-antibodies to an enzyme called ADAMTS13, which cleaves von Willebrand Factor. Loss of this enzyme causes platelet clumping and red blood cell destruction that are the hallmarks of TTP.

Ciphergen and OSU in November unveiled an agreement to develop and clinically validate a diagnostic test to detect TTP. OSU and Ciphergen said they would optimize the assay to measure enzyme and antibody inhibition activity and would jointly conduct multi-center studies to validate the test.

“Continual monitoring, or testing, of the enzyme that is deficient in patients with TTP aids physicians in determining disease activity so that they may apply the proper course of treatment,” said Haifeng Wu, MD, assistant professor of pathology and medicine and director of clinical coagulation laboratory at the OSU Medical Center . “In this initial study population, our TTP assay helped us evaluate recurrence of disease and patient response to therapy, resulting in improved clinical outcome.”

Twenty-one patients treated with concurrent cyclosporine and plasma exchange (CSA/PE) were monitored using Ciphergen’s SELDI-based test to measure response to therapy and to determine the best course of treatment. Each patient was tested weekly during the active disease phase and during initial clinical remission. After achieving a sustained clinical remission, patients were then tested quarterly.

Continual laboratory monitoring, along with clinical assessment, enabled physicians to make appropriate adjustments to the treatment regimen, resulting in improved clinical outcome.

“These studies further contribute towards our understanding of the pathogenesis of this disease,” said Eric Fung, MD, PhD., chief scientific officer for Ciphergen. “We intend to apply these promising results towards a larger patient population to further validate the assays’ clinical utility for monitoring disease activity and for evaluating treatment response in patients with TTP.”

In other news from the ASH meeting:

Aldagen (Durham, North Carolina) presented data from a clinical trial using its Aldesort product to isolate stem cells from cord blood. The trial is being conducted by Joanne Kurtzberg, MD, a physician at Duke University (Durham, North Carolina) who pioneered the use of umbilical cord blood as a treatment for fatal childhood cancers and genetic diseases in 1993.

Aldagen’s Aldesort product is a set of reagents that can be used with cell sorting systems to isolate a highly potent population of stem and progenitor cells from human bone marrow, peripheral blood and cord blood. The chemistry incorporated into the Aldesort is designed to enrich a unique population of stem and progenitor cells from cord blood that contribute to neutrophil and platelet engraftment and to immune reconstitution following transplantation, the company said.

In an interim analysis, 11 pediatric patients with cancer or genetic diseases were transplanted with unrelated donor umbilical cord blood and a supplement of cord cells isolated using Aldesort. Overall survival at 180 days was 90.9%, compared to an overall survival at 180 days of 57% in the COBLT study. The cumulative incidence of neutrophil engraftment by day 42 was 90.9% (p=0.001) and platelet engraftment by day 100 was 79.5% (p=0.003).

The primary goal of the clinical study is to determine if transplanting those enriched cells is safe. The study also is expected to indicate if transplanting the cell populations could result in accelerated engraftment and lead to more favorable clinical outcomes compared to a historical control group from the Cord Blood Transplantation Trial (COBLT) study, a multicenter Phase II study sponsored by the National Heart, Lung and Blood Institute .

“The findings of this study once again show the promise of transplanting stem cells from umbilical cord blood to treat children with resistant cancers and genetic diseases,” said Kurtzberg. Umbilical cord stem cells are located in the umbilical cord and placenta of a newborn at birth. After the baby has been delivered and the umbilical cord has been cut, blood is drawn from the umbilical cord. Umbilical cord stem cells are not embryonic stem cells.