Navigation Links
HIV drug reduces graft-versus-host disease in stem cell transplant patients, Penn study shows
Date:12/13/2011

(SAN DIEGO) -- An HIV drug that redirects immune cell traffic appears to significantly reduce the dangerous complication graft-versus-host disease (GvHD) in blood cancer patients following allogeneic stem cell transplantation (ASCT), according to new research from the Perelman School of Medicine at the University of Pennsylvania that will be presented today at the 53rd American Society of Hematology Annual Meeting. Standard GvHD treatments suppress the immune system, reducing but not eliminating the risk of developing the common problem. In the current trial, treatment with the HIV drug maraviroc dramatically reduced the incidence of GvHD in organs where it is most dangerous -- without compromising the immune system and leaving patients more vulnerable to severe infections.

"There hasn't been a change to the standard of care for GvHD since the late 1980s, so we're very excited about these results, which exceeded our expectations," says Ran Reshef, MD, an assistant professor in the division of Hematology-Oncology and a member of the Hematologic Malignancies Research Program at Penn's Abramson Cancer Center. "Until now, we thought that only extreme suppression of the immune system can get rid of GvHD, but in this approach we are not killing immune cells or suppressing their activity, we are just preventing them from moving into certain sensitive organs that they could harm."

Reshef and colleagues will present results showing that maraviroc is safe and feasible in ASCT patients those who receive stem cells from a healthy donor -- and that a brief course of the drug led to a 73 percent reduction in severe GvHD in the first six months after transplant, compared with a matched control group treated at Penn during the same time period (6 percent developed severe GvHD vs. 22 percent, respectively).

"Just like in real estate, immune responses are all about location, location, location," Reshef says. "Cells of the immune system don't move around the body in a random way. There is a very distinct and well orchestrated process whereby cells express particular receptors on their surface that allow them to respond to small proteins called chemokines. The chemokines direct the immune cells to specific organs, where they are needed, or in the case of GvHD, to where they cause damage."

Thirty-eight patients with blood cancers, including acute myeloid leukemia, myelodysplastic syndrome, lymphoma, myelofibrosis, and others, enrolled in the phase I/II trial. All patients received the standard GvHD prevention drugs tacrolimus and methotrexate, plus a 33-day course of maraviroc that began two days before transplant. In the first 100 days after transplant, none of the patients treated with maraviroc developed GvHD in the gut or liver. By contrast, 12.5 percent of patients in the control group developed GvHD in the gut and 8.3 percent developed it in the liver within 100 days of their transplant.

The differential impact of maraviroc on those organs indicates that the drug is working as expected, by limiting the movement of T lymphocytes to specific organs in the body. Maraviroc works by blocking the CCR5 receptor on lymphocytes, preventing the cells from trafficking to certain organs. The researchers saw no effect on skin GvHD, so they theorize that the CCR5 receptor might be more important for sending lymphocytes into the liver and the gut than for the skin.

After 180 days, the benefit of maraviroc appeared to be partially sustained in patients and the cumulative incidence of gut and liver GvHD rose only to 8.8 percent and 2.9 percent, respectively. The cumulative incidence in the control group, however, remained higher, at 28.4 percent for gut and 14.8 percent for liver GvHD. Based on those data, the research team plans to try a longer treatment regimen with maraviroc to see if they could prolong the protective effect.

Maraviroc treatment did not appear to increase treatment-related toxicities in these patients, nor did it alter the relapse rate of their underlying disease.

David Porter, MD, professor of Medicine and director of Blood and Marrow Transplantation in the Abramson Cancer Center, and Robert Vonderheide, MD, DPhil, associate professor of Medicine and Associate Director for Translational Research at the Abramson Cancer Center, are the senior authors of the study.


'/>"/>

Contact: Holly Auer
holly.auer@uphs.upenn.edu
215-200-2313
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Service Foods Reduces its Carbon Footprint and Grows Sales
2. Health Care Reform Report Covers Uninsured, Reduces Costs
3. New cardiac CT technology drastically reduces patient radiation exposure
4. Accelerated radiation therapy reduces toxicity in patients with advanced head and neck cancers
5. Targeted delivery of losartan reduces liver inflammation and scarring
6. Drug dramatically reduces nausea and vomiting in bone marrow transplant patients
7. Soccer reduces risk of falls and bone fractures
8. Pioneering treatment reduces disability in premature babies with serious brain hemorrhage
9. New drug candidate reduces blood lipids
10. PSA Test Reduces Prostate Cancer Deaths by 40%
11. New technique reduces tobacco smoke damage to lungs in mice
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/23/2017)... ... January 23, 2017 , ... Gynecology Associates ... and gynecological services for women of all ages. The staff of ... variety of reproductive services from routine health screenings to diagnosing and treating female ...
(Date:1/23/2017)... ... January 23, 2017 , ... “Life Under Blankets”: an entrancing story about ... “Life Under Blankets” is the creation of published author, Kimberly Mitchell, who earned her ... She went on to pursue a master’s degree in education in the field of ...
(Date:1/22/2017)... FL (PRWEB) , ... January 22, 2017 , ... Zifam ... customers across the world, recently met with big-name retail buyers at the January ECRM ... evidence of efficacy and uses the utmost safety standards in all of its creations ...
(Date:1/21/2017)... ... 2017 , ... Salveo for life, a company that distributes an effervescent lime-flavored ... States as part of its presence to expand its market reach. , Using a ... productions of nasty toxins as a result of drinking alcohol, eliminating those toxins quickly, ...
(Date:1/21/2017)... ... January 21, 2017 , ... Pacifica Graduate Institute’s Alumni Association ... of events for its annual meeting “Coming Home 2017,” an activity-packed weekend of ... 2017” will be held on Friday January 27 through Sunday, January 29, 2017 ...
Breaking Medicine News(10 mins):
(Date:1/21/2017)... -- Faruqi & Faruqi, LLP, a leading national securities law firm, ... KMPH ) of the federal securities class action ... and underwriters of the Company,s April 16, 2015 Initial Public ... The lawsuit has been filed in the ... County on behalf of all those who acquired ...
(Date:1/20/2017)... 2017  Ethicon Endo-Surgery, Inc. announced today ... Inc., a privately held medical device company ... used in operating rooms worldwide. The acquisition ... energy devices with Megadyne,s innovative portfolio of ... in Ethicon,s goal to deliver the most ...
(Date:1/20/2017)... Jan. 20, 2017  Palladian Health, a leading ... the launch of an opioid management program which ... opioids and helps stem the growing tide of ... to treat chronic non-cancer pain (back pain, neck ... and lack of evidence regarding long-term effectiveness. ...
Breaking Medicine Technology: