ATLANTA — With an estimated 20,000 in attendance, the 49th annual meeting of the American Society of Hematology (Washington) ended yesterday with a bang, not a whimper.
Tuesday’s offerings might have been slightly lighter than the previous days, but they were certainly heavier in terms of importance.
The centerpiece of the day’s events was a panel discussion on cancer stem cells, or those cells that have properties of adult stem cells, particularly the abilities to self-renew and differentiate into multiple cell types. These cells persist in tumors as a distinct population that likely causes disease relapse and metastasis — they are the only cells capable of, by themselves, giving rise to new tumors.
John Dick, PhD, of the University Health Network (Toronto), Hans Clevers, MD, PhD, of Hubrecht Institute (Utrecht, the Netherlands) and Craig Jordan, PhD, of University of Rochester Medical Center (Rochester, New York) were the panelists discussing the stem-cell topic.
The main concern regarding the cancer stem cell philosophy is if researchers are targeting the right kind of cell. Most of the existing cancer treatments are developed on animal subjects, where these treatments are able to promote tumor shrinkage and are deemed effective.
But animals don’t provide a complete model of human disease. Some of the animal test subjects only have a short life span, not long enough to see if there is a tumor relapse, according to cancer stem cell studies.
“We don’t have enough markers in these blood cells to determine the phenotype,” said Jordan. “Certainly there are a variety of different activation pathways [for the cancerous cells].”
Another issue comes from the fact that the efficacy of cancer treatments, in the initial stages of testing, often is measured by the amount of tumor mass it can kill off.
As cancer stem cells make up a very small proportion of the tumor, this doesn’t necessarily select for drugs that act specifically on the stem cells. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate new cells. A population of cancer stem cells, which gave rise to it, remains untouched and may cause a relapse of the disease.
“We seem to be holding on for the search of a ‘magic bullet’ in terms of treatment,” said a member of the audience.
But according to the panelists the development of a magic bullet or specific therapies that are targeted at cancer stem cells is still a good bit off, even though important strides have been made thus far.
The problem with targeting these cells can be found in the composition of normal tissue stem cells. These stem cells are naturally resistant to chemotherapeutic agents — they have various pumps (such as MDR) that pump out drugs, DNA repair proteins and they also have a slow rate of cell turnover (chemotherapeutic agents naturally target rapidly replicating cells).
Also, there has been a lot of research into finding specific markers which may differentiate cancer stem cells from normal cancer cells, with some success. This may allow drugs to directly target the stem cells.
“The challenge is to collect a large amount of cells and interrogate these cells rigorously,” Dick said. “There has to be an effort to bank large cells and then we’ll be able to ascertain these models more properly.”
In other conference news:
• CSL Behring (Melbourne, Australia) reported the results of a pre-clinical study showing for the first time that it’s feasible to genetically fuse Factor VIIa (FVIIa) to human albumin, in prolonging the half-life of this therapeutic protein while retaining its biologic activity.
“A major unmet need in hematology is improving the pharmacokinetic parameters of coagulation factors, such as half-life, while retaining full hemostatic activity,” said Stefan Schulte, head of pre-clinical R&D at CSL Behring and lead investigator of the study. “The pharmacological properties of rVIIa-Fp seen in our study could one day facilitate a single dosing regimen of one injection per bleeding event, as well as significantly reduce the number of injections hemophilia patients with inhibitors need during surgical interventions.”
• Sanofi-Aventis (Paris) released a study showing that low-molecular weight heparin (LMWH) was associated with reduced hospital costs of venous thromboembolism (VTE) Treatment compared with unfractioned heparin (UFH). The study shows that total hospital direct medical costs associated with the treatment were reduced $550 per patient.
The analysis included 38,664 patient discharges, with 53% (20,577) receiving LMWH and 47% (18,807) receiving UFH. Among those patients who received LMWH, 97.3% (20,577) received Lovenox, with the remaining 2.7% receiving other LMWHs.
The two groups were similar in clinical and demographic characteristics. The average length of hospital stay for the UFH group was 1.1 days longer (5.7 days vs. 4.6) days. After adjustments for co-variates, the average total direct hospital costs were $3,618 for UFH and $3,068 for LMWH.