The US Food and Drug Administration (FDA) said that Genzyme voluntarily recalled nine lots of Thymoglobulin, its drug which treats transplant rejection for patients with kidney transplants.

The recall is due to one lot of the drug failing a periodic stability test, which is a study that checks the shelf life of a drug within specified conditions.

Currently, there have been no adverse events reported and Genzyme has not acknowledged any safety risks for patients that have taken the affected lot.

“Genzyme has not identified any new safety risk to patients who have received Thymoglobulin from the implicated lot numbers, and there are no confirmed safety issues directly associated with the stability failure,” the FDA stated in their recall notice.

They found that the raw material that is used to make Thymoglobulin was the cause of change in the shelf life of the drug. The FDA stated that other lots of drugs manufactured with the same quality of raw material are being recalled as well because of the potential risk of stability failure.

Source: FDA

Last Updated: 8/29/12; 10:00am EST

A phase III study recently published in the American Journal of Transplantation found that patients who received the experimental drug, RAD001 (everolimus), with reduced tacrolimus a month after liver transplant experienced equal efficacy and superior kidney function to patients taking the tacrolimus alone.

RAD001 is currently being investigated for prevention of organ rejection in adult patients who are receiving a liver transplant.

“In this study, patients treated with RAD001 plus reduced tacrolimus showed superior differences in renal function, compared to the tacrolimus control group, as early as one month after the introduction of RAD001, with no apparent decline over the one-year study period,” Dr. John Fung, MD, PhD, director, Transplantation Center, Cleveland Clinic Foundation said. “Despite early and reduced tacrolimus exposure, we did not see any compromise in the control of rejection, and that is very encouraging.”

The study met the revised primary endpoint, the composite efficacy failure rate of tBPAR, graft loss or death. Additionally, the study met the secondary endpoint, which showed non-inferiority in change in renal function.

The most common adverse events for those taking RAD001 plus reduced-exposure tacrolimus were diarrhea, headache, peripheral edema, hypertension, nausea, abdominal pain, fever, hepatitis C, tremor and fatigue.

The Food and Drug Administration (FDA) accepted Novartis’ filing for RAD001 for prevention of organ rejection in adult liver transplant patients. The company expects the FDA will make a decision by the last quarter of 2012.

Last Updated: 8/13/12; 3:20pm EST

The discovery that human lung stem cells do exist, contrary to much current scientific thinking, is likely to lead to completely new treatments that repair and regenerate damaged tissue in patients with chronic lung diseases, but not for some time because there is still a lot of work to be done, said the authors of a paper published online this week in the New England Journal of Medicine.

Corresponding author Dr Piero Anversa, director of the Center for Regenerative Medicine at Brigham and Women's Hospital (BWH) in Boston, Massachusetts, and colleagues, found that the human lung stem cell is self-renewing, plays an important role in regenerating tissue and and may also help repair damaged lung cells.

They also found that the stem cell can form and integrate various biological structures of the lung, including alveoli, the tiny breathing sacs where oxygen and carbon dioxide are exchanged between air and blood; bronchioles, the small airways that connect the alveoli to the main airways; and pulmonary vessels, the blood vessels that serve the lungs.

Anversa told the media that they have for the first time found and described a "true human lung stem cell".

"The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung," he added.

Co-author Dr Joseph Loscalzo, chair of the Department of Medicine at BWH said they were "excited about the impact this discovery could have on our ability to regenerate or recreate new lung tissues to replace damaged areas of the lungs".

However, he said more research is now needed to build on these "critical first steps" before work can start on developing new clinical treatments for people with currently untreatable lung diseases.

In their paper the researchers describe how they isolated the the human lung stem cell from lung tissue taken from surgical samples and, working with cultures and laboratory mice, they then tested what they were capable of doing.

In culture ("in vitro"), they showed that the stem cell could divide into new stem cells and also into cells that would turn into various types of lung tissue.

And then, after injecting the stem cells into mice with damaged lungs ("in vivo"), they found they differentiated and formed various biological structures in the lungs, including new bronchioles, alveoli and pulmonary vessel cells. Not only did they make the new structures but they also wove them into the mice's existing lung tissue.

In a final stage of the study, the researchers took tissue from the treated mice, isolated stem cells from it, and then used them in new mice with the same results.

Thus they were able to show that that the cell they discovered was a "true stem cell" because it met all three criteria for categorizing a stem cell: it is self-renewing, it forms many types of lung cell, and, with the last part of the experiment, it is transmissible.

The discovery is a challenge to current scientific thinking about lung cells, says Dr Harold A. Chapman, from the University of California, San Francisco, in an accompanying editorial. Until this study, scientists thought there were no cells in the lung that could differentiate into the various types of lung cell.

Chapman, an expert in pulmonary and critical care medicine, writes that parts of the "extensive experiments" that the researchers report may even prove to be wrong, but overall, the findings are "convincing".

A grant from the National Institutes of Health helped pay for the study.

"Evidence for Human Lung Stem Cells."

Jan Kajstura, Marcello Rota, Sean R. Hall, Toru Hosoda, Domenico D'Amario, Fumihiro Sanada, Hanqiao Zheng, Barbara Ogórek, Carlos Rondon-Clavo, João Ferreira-Martins, Alex Matsuda, Christian Arranto, Polina Goichberg, Giovanna Giordano, Kathleen J. Haley, Silvana Bardelli, Hussein Rayatzadeh, Xiaoli Liu, Federico Quaini, Ronglih Liao, Annarosa Leri, Mark A. Perrella, Joseph Loscalzo, and Piero Anversa.

New England Journal of Medicine, 2011; 364 (19): 1795-1806

A new study of heart-transplant-registry data suggests that the highest-risk patients should be funneled to a relatively small group of institutions that perform the most transplant procedures [1].

Here at the American Association for Thoracic Surgery 2011 Annual Meeting, Dr George J Arnaoutakis (Johns Hopkins University, Baltimore, MD) presented an analysis of nine years' worth of data from the United Network for Organ Sharing (UNOS) database showing that institutional volume is an "effect modifier" on the association between a patient's risk factors and chances of surviving at least a year after the transplant. The highest-risk patients have "an exceedingly high mortality rate" when transplanted at low-volume centers but a significantly lower risk of near-term mortality when treated at a higher-volume center. The transplant center's procedure volume matters less for low-risk recipients, Arnaoutakis said.

Earlier studies have examined the relationship between centers' procedure volume and transplant outcomes, but these studies were unable to fully account for differences in the patients' underlying risk, according to Arnaoutakis. So his group developed and validated a 40-point heart-transplant-recipient risk index system called IMPACT for predicting the short-term mortality risk of heart-transplant recipients. Each one-point increase in IMPACT risk score was associated with a 13% increase in the odds of one-year mortality. They then used regression analysis to examine the effect of risk and center volume on mortality in 17 211 transplant patients treated at 141 centers from 2000 through 2009.

They broke up the centers in the UNOS database into tertiles. There were 923 patients (5.4%) treated at low-volume centers that performed fewer than 6.2 transplants annually. The medium-volume centers performed between 6.3 and 14 procedures a year on a total of 4720 patients (27.4%). The high-volume centers performed between 14.1 and 75.2 procedures a year for a total of 11 568 patients (67.2%).

In the low-risk-patient stratum, there was no significant difference in one-year survival at high-, medium-, and low-volume centers--around 92% in all centers (p=0.7) But the difference was significant in the high-risk-patient group (p<0.001). Expected one-year survival for the highest-risk patients is 78.8%, 74.6%, and 64.4% for the high-, medium-, and low-volume centers, respectively.

As continuous variables, interaction between center volume and transplant-recipient risk was statistically significant, such that as recipient risk increases, decreasing center volume amplifies the odds of one-year mortality, Arnaoutakis said. Logistic regression analysis shows that, holding risk score constant, the odds of one-year mortality at the medium-volume centers was 20% higher than at the high-volume centers and 58% higher at the low-volume centers than at the high-volume centers (p<0.001 for all comparisons.) He also noted that there appears to be a "plateau" between 20 and 25 transplants per year, above which additional center volume does not significantly improve outcomes.

"These data strongly support a mandate for transplantation of high-risk recipients at high-volume centers only," Arnaoutakis said.

Commenting on the study at the conference, Dr Duane Davis Jr (Duke University, Durham, NC) pointed out that despite the overall trend, there were some low-volume centers that had consistently good outcomes. "We shouldn't be in the business of shutting down programs, but thinking about how [we can] improve the quality of all the programs [and finding] what [we can] learn from this type of data-set analysis that says, 'if you're going to be in the business of heart transplant, these are the critical items that you need to be really successful.' "

Arnaoutakis agreed. "This study's intention and these findings are not meant to impugn centers of any volume whatsoever. . . . These findings don't prove any causation but show associations. What we need to pursue from here on is to identify the processes of care that we believe are intimately involved with [the best results]."

To better understand what makes some transplant centers more successful than others, Arnaoutakis suggested further studies of specific institutions that collect data on even more variables than UNOS. For example, his center has collected data on its patients showing that the distance patients live from the transplant center is associated with the rate of transplant rejection. He also pointed out that the UNOS database does not have much on the experience of specific surgeons or the quality of perioperative care at each center, but "some of the pathways and structures set up at various ICUs may explain what is causing these differences."