Featured Research

from universities, journals, and other organizations

Drug Shows Promise In Treating Severe, Often-Lethal Complication Of Stem Cell Transplants

Date:
September 5, 2002
Source:
Dana-Farber Cancer Institute
Summary:
A study led by researchers at Dana-Farber Cancer Institute has shown that a drug extracted from porcine intestinal tissue reduced the risk of death in patients who experienced a severe and often-fatal complication of stem cell transplants.

BOSTON – A study led by researchers at Dana-Farber Cancer Institute has shown that a drug extracted from porcine intestinal tissue reduced the risk of death in patients who experienced a severe and often-fatal complication of stem cell transplants. The experimental drug defibrotide reversed severe veno-occlusive disease (VOD) of the liver in more than one third of the stem cell transplant recipients enrolled in the study. VOD is a type of potentially fatal liver damage that can result from the high doses of chemotherapy given prior to a transplant. The findings, which will be published in the Dec. 15 issue of Blood, have been posted as a "First Edition Paper" on the journal's web site (www.bloodjournal.org).

"Stem cell transplant patients suffering from severe veno-occlusive disease are at a very high risk of death, with a mortality rate in excess of 90 percent. The results from this study are compelling, especially given the remarkable safety of the drug in this extremely sick population," says Paul G. Richardson, MD, a hematologic oncologist at Dana-Farber who led the multi-center study. "This trial, which is the largest of its kind to date, confirms prior reports from smaller studies, and provides a strong platform for us to move forward with further trials of defibrotide, both in therapy for established VOD and its prevention."

Five to 60 percent of stem cell transplant patients develop VOD, which ranges in severity from mild and reversible to severe and almost always fatal. Stem cell recipients have an elevated risk for VOD due to the high-dose chemotherapy they undergo prior to transplantation and the type of transplant they have, with allogeneic (unrelated donor) transplant recipients being at greater risk than autologous (related donor) patients. Chemotherapy drugs can damage the cells lining the small blood vessels in the liver as well as liver cells. This disrupts the liver's circulation, causing it to swell painfully, and results in VOD. Patients with VOD usually become jaundiced and bloated, and they are at risk for other organs to fail, such as the kidneys and lungs.

Under a research protocol allowing it to be used on an emergency basis, defibrotide was given to 88 transplant patients who had severe VOD and multi-system organ failure. The drug reversed VOD completely in 32 patients (36 percent), and 31 patients (35 percent) survived at least 100 days after transplant, a milestone used to determine transplant success. Less than 10 percent of these patients typically would have been expected to survive 100 days post-transplant.

The younger patients in the trial fared better than those who were older, explains senior author Eva C. Guinan, MD, director of the Pediatric Stem Cell Transplant Program at Children's Hospital Boston and a pediatric oncologist at Dana-Farber. Many of the survivors were younger than 18, including infants as young as 8 months. "We've had some children in the Intensive Care Unit with incredibly severe VOD, who were on ventilators and dialysis, and who are now long-term survivors with excellent function," says Guinan, who is also an associate professor of pediatrics at Harvard Medical School.

VOD is more common in transplant centers that accept sicker patients with a poorer outlook, Richardson says, and less common in centers that include only the best candidates. Some individuals are more susceptible to VOD than others, but it is not possible to always identify those patients ahead of time.

Previously, doctors administered clot-busting drugs like t-PA and heparin to treat VOD, but the drugs caused severe bleeding and were ineffective in patients with multi-system organ failure. In this study, defibrotide, which is a single stranded piece of DNA that is selectively active on the surface of small blood vessels and repairs blood vessel injury, did not cause any serious bleeding and side effects, such as hot flashes, were mild.

Richardson and his colleagues currently are conducting a randomized, prospective trial of defibrotide to verify this study's findings and determine the best dose. "Given the drug's favorable safety record and promising activity, we plan to next study this drug as a prophylactic agent in patients undergoing transplant. In the future, this may allow us to treat patients who otherwise would be denied transplants because of their high risk of VOD," says Richardson, who is also an instructor at Harvard Medical School.

Co-authors of the study include researchers at Dana-Farber, Brigham and Women's Hospital, Children's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, and Harvard Medical School, all in Boston; Columbia University, New York; Loyola University Medical Center, Chicago; University of Colorado Health Center, Denver; Duke University Medical Center, Durham, NC; Johns Hopkins Oncology Center, Baltimore; and Fred Hutchinson Cancer Research Center, Seattle.

The study was funded in part by the Orphan Products Development Program of the Food and Drug Administration. Defibrotide is manufactured by Gentium SpA of Como, Italy.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Drug Shows Promise In Treating Severe, Often-Lethal Complication Of Stem Cell Transplants." ScienceDaily. ScienceDaily, 5 September 2002. <www.sciencedaily.com/releases/2002/09/020905063814.htm>.
Dana-Farber Cancer Institute. (2002, September 5). Drug Shows Promise In Treating Severe, Often-Lethal Complication Of Stem Cell Transplants. ScienceDaily. Retrieved July 26, 2014 from www.sciencedaily.com/releases/2002/09/020905063814.htm
Dana-Farber Cancer Institute. "Drug Shows Promise In Treating Severe, Often-Lethal Complication Of Stem Cell Transplants." ScienceDaily. www.sciencedaily.com/releases/2002/09/020905063814.htm (accessed July 26, 2014).

Share This




More Health & Medicine News

Saturday, July 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins