School without germs

August 27, 2007

School without germs

A video link is a window of learning for a boy with fragile health.

By TOM MARSHALL, Times Staff Writer
Published August 27, 2007


SPRING HILL – Mrs. Lewis had a perfect voice, but her video image was a mess – doubling at times, coming and going, pixels dancing. ¶ Kevin O’Connell saw a few kids dart past the teacher as the clock struck 9 a.m., searching for their seats in the third-grade class at Spring Hill Elementary. ¶ He peered intently at his screen, and they peered back at him. ¶ “Good morning, Kevin!” Mrs. Lewis said, as the class came to order. “Are you ready?” ¶ He nodded. ¶ Technical glitches aside, they were live.Nine years ago, Kevin was born with a rare immune system disorder, Hyper-IgM Syndrome. Without a bone marrow transplant, like the one his body rejected at age 4, a common virus — a stranger’s careless sneeze, a feverish classmate — could lead to a fatal infection.His parents have strictly limited his contact with the outside world. Shopping trips are fine if he wears a mask, and friends can visit if they’re not sick. During flu season, he lives at home in a virtual lockdown.

Germ-filled schools were out of the question until Thursday, when Hernando County schools rolled out a videoconferencing system to connect Kevin with his peers and teachers. It was the first time he had ever venturedinside a school.

The public-address system was squawking over his tiny speaker. Time for the Pledge of Allegiance.

Kevin leapt out of his chair, a mile from his classmates and just down the hall from his own bedroom, and pledged.

– – –

He was 21 months old when his mother, Joan, first noticed a problem.

“He got these huge oral ulcers,” she recalled. “I said, ‘There’s something wrong with this child.’ They said, ‘No, no, no, it’s just a virus.’ ”

Mom was right. As it turned out, she was also the carrier of Kevin’s disease, in which blood cells that normally fight off infections fail to do so.

Joan turned her son’s illness into a full-time job, researching the dismal statistics — few with Hyper-IgM live past their 20s without a successful bone marrow transplant — and hunting down researchers for an effective treatment.

Beginning in kindergarten, Kevin had lessons at home with a visiting district teacher.

Joan also began the three years of talks with school officials that led to the purchase of videoconferencing equipment with $60,000 in state grants. Officials hope to eventually make the system available to homebound students in all 21 district schools.

These days, she works part-time at Publix to keep her medical benefits, and has never lost a coverage fight with Blue Cross/Blue Shield. Her husband, John, a retired county worker, stays at home with Kevin when she can’t.

Kevin’s doctor-approved treatment includes weekly antibody injections and reduced human contact. Some children with the disease attend school, getting monthly injections and lots of antibiotics, but they’re constantly sick.

“Kevin’s only had a cold twice in his whole life, which is unheard of,” Joan said.

For now, she’s not willing to risk another body-ravaging bone marrow transplant, such as the one Kevin’s oldest brother gave him.

“He looks great, he looks wonderful,” she added. “It’s just that inside he’s missing an immune system. So we’re preserving him till they find a cure.”

– – –

There were network problems at BellSouth, but Christina Lewis forged on with the day’s lessons.

“I don’t want you to fret about getting your work done today,” she told Kevin, as the class prepared for reading. “I want you to get used to using your camera.”

He toggled the camera around the room, peeking at his classmates, while his father tried to keep him on task.

“Dad, that’s how you zoom it,” Kevin said, pushing his father’s hand from the controls. “Don’t press that.”

By 11 a.m., everyone was tired. It had been a long, intense morning.

“She wants you to do the whole page,” John said. “Let’s go. Zero plus what equals seven? I’m helping to try and get you started.”

“I didn’t eat breakfast,” Kevin complained.

“I tried to get you to eat but you didn’t want to,” his dad said. “Now you’re stuck till lunch.”

A few minutes later: “Good job!” John said. “See? You’ve just got to stick with it.”

– – –

Walking down the street, Kevin might pass for an ordinary 9-year-old boy: freckles, one tooth missing up front, an affinity for rapid chatting.

Unlike the famous “Boy in the Bubble,” the late David Vetter — whose more serious condition, Severe Combined Immunodeficiency Syndrome, prompted his parents and doctors to isolate him in a plastic bubble in the 1970s — Kevin gets out occasionally.

There are the shopping trips, and once a year the family goes ice skating at an empty rink. Neighborhood children can attend Kevin’s birthday party every August, as long as they’re healthy and haven’t gotten live vaccines lately.

They went bowling once, but Kevin caught a cold and wound up in the hospital with tubes down his throat, terrified.

“He said, ‘Bowling isn’t worth it,’ ” Joan said. “We got him a ball and shoes, and they’ve been retired ever since.”

Inevitably, there are plenty of rules at Kevin’s house. Everyone washes hands upon entering. And both Joan and John repeat a mantra to strangers: “We don’t shake hands around here.”

Perhaps as a consequence of such restrictions, Kevin enjoys a bit more freedom to view the world through TV’s distorted lens. Pro wrestling reigns in Kevin’s bedroom.

“Sometimes it’s real, sometimes it’s fake,” he said, showing off his collection of posters and prize belts. “I can’t even tell when it’s fake. My friend Josh likes it, Joey likes it, and Jeremy a little bit.”

Has he ever wrestled for real?

“We can’t wrestle, my parents say that,” Kevin said, lowering his voice and grinning. “When they’re not watching, we kind of do.”

But they always wash their hands, he added.

Through TV, he’s also gained a view of the world in which schools are chaotic places, where girls are always sweet and boys throw spitballs at the teacher.

“I’m lucky I’m right here,” Kevin said in his kitchen, the day before school began. “Because there could be bullies.”

– – –

The afternoon was winding down as Mrs. Lewis moved on to the science lesson. There would be a fossil-making activity with clay one day soon, and a lab on comparing plants. Kevin could take part in it all, she said.

“Everyone’s going to come by your camera and hold up some stuff, so you can compare just like we do,” Mrs. Lewis told him.

“I just want to ask one thing,” Kevin said. “The science project can be anything, right?”

He knew just what he wanted to do: something that involved engineering, hopefully with his Legos.

Soon enough, it was time to go.

“Kevin, you’re dismissed,” she said, as his new classmates waved. “Everyone say bye.”

It was a good day.

Tom Marshall can be reached at tmarshall@sptimes.com or 352 848-1431.

What is Hyper-IgM Syndrome?

For most people, T cells and B cells in the bloodstream defend the body against infection. But women who carry the gene for Hyper-IgM on an X chromosome can pass it on to their offspring. Since females have two X chromosomes and males have only one, it’s the males who bear the full brunt of the disease.

Source: St. Jude Children’s Research Hospital; Gene Reviews/University of Washington

linkback url: http://www.sptimes.com/2007/08/27/Hillsborough/
School_without_germs.shtml


Gene Therapy and the History of Organ Transplantation

August 27, 2007

Gene Therapy and the History of Organ Transplantation

This article is from Wired Science a blog network.

By Brandon Keim August 27, 2007 | 4:41:32 PMCategories: Gene Therapy, History, Medicine & Medical Procedures

Murray When something goes wrong in a gene therapy trial, it’s front page news — yet when something goes wrong in a trial involving a drug or surgical technique, people hardly even notice.

This double standard is something that frustrates many researchers, and with good reason. They’re worried that the field will wither before it has a chance to succeed. Even though gene therapy research is nearly two decades old, other now-mainstream treatments took just as long if not longer to develop.

As Theodore Friedmann, former head of the American Society of Gene Therapy, wrote in the Hastings Center’s Bioethics Forum:

Modern medicine relies on many forms of therapy that, during their development, went through long periods of setbacks and failure before the underlying conceptual and technical unknowns were solved. These periods often included patient injury and even death. But today’s medicine would be impoverished if it lacked these important technologies – disease-fighting techniques such as bone marrow transplantation, cancer chemotherapy, and the use of monoclonal antibodies for the design of targeted drugs. Bone marrow transplantation – which now saves so many lives – began clinical trials in 1958. By the early 1970s, the survival rate from the procedure was only around 1 percent. It was 32 years before the technology earned its principal discoverer, Professor Donnel Thomas, a Nobel Prize in medicine. Similarly, chemotherapy for childhood leukemia began in 1948, but the cure rate remained below 10 percent well into the 1960s.

I’m just finishing up a feature on gene therapy and its use in diseases that aren’t immediately life threatening. This double standard is something that came up a few times in interviews, and — frustratingly — there wasn’t space in the article to do it justice.

But that’s the beauty of blogs, and I wanted to take a moment to talk about this issue.

Now, I don’t mean to imply that tragedies like that of Jesse Gelsinger or — quite possibly — Jolee Mohr should be downplayed or written off as inevitabilities. Just because experimental therapies are are risky doesn’t mean those risks should be minimized.

Scientists are right, however, that the public fear of gene therapy and other biotech therapies is exaggerated. Unfortunately, that’s just the way it is — unfair, but unavoidable.

“Like it or not, gene therapy has fallen into a situation where it’s been high-profile, heavily hyped for promise, and wound up with no real demonstrable successes after more than a decade of effort,” University of Pennsylvania bioethicist Arthur Caplan told me during an inteview for the story.

As a result, said Caplan, gene therapy is at a crossroads. Will its promise be fulfilled, or be abandoned just short of success? It’s quite possible that gene therapy, treated with suspicion by investors and the public and journalists, will lose funding and interest, with researchers electing to pursue other, less-controversial fields.

If that happens, it would likely be tragic. But at the same time, the examples — particularly that of organ transplantation — that are used by scientists and doctors who counsel patients involve life-or-death conditions. If early organ transplants had been tested on people who had other options, the resulting outcry could have halted research altogether.

However frustrating it might be, the prudent course is to focus gene therapy research on critical conditions, and take extra care when designing trials for treating less-severe conditions. In some cases — such as moderate rheumatoid arthritis — regulators might be well-advised to temporarily reject gene therapy altogether.

This is bound to frustrate many people, and perhaps it will slow gene therapy research even more. But in an environment where mistakes are inevitable and high-profile, it may be the only way for gene therapy to survive long enough to succeed.

linkback url: http://blog.wired.com/wiredscience/2007/08/
gene-therapy-an.html#more


Infants who undergo bone-marrow transplantation may pay a price in a decline in communication and other developmental skills.

August 24, 2007

SAN FRANCISCO, Aug. 24 — Infants who undergo bone-marrow transplantation may pay a price in a decline in communication and other developmental skills.

Action Points
* Explain to parents of infants who may need bone marrow transplantation that it has been known to cause some developmental delays.

* This study was published as a poster at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

The long isolation inherent in the procedure is the culprit, said Linda Ruthruff, Ph.D., a post-doctoral fellow in infant development at San Francisco General Hospital.

“Infants younger than two at the time of bone marrow transplantation are at risk of declines in IQ and for slowing the rate of acquisition of developmental skills,” she and colleagues reported at the American Psychological Association meeting here.

However, Dr. Ruthruff said her study of 54 infants who underwent the procedure for cancer or immunological diseases indicated that factors related to lessening of impairment is related to a younger age and a shorter period of isolation.

“Our study specifically examined how bone-marrow transplantation procedures impact the communication and socialization skills of these children,” she said at her poster presentation.

“While survival of these children is improving,” Dr. Ruthruff said, “we need to know if therapeutic interventions can improve functioning if outcomes are poor. There is very little information in the bone-marrow transplantation literature regarding infant outcome. We know family life is disrupted.”

Dr. Ruthruff and researchers at the Pacific Graduate School of Psychology and the University of California at San Francisco said that their exploration of the psychosocial development of these children revealed significant deficits in IQ development, declines in behavior scores, and impaired communication skills.

In her group of patients, 26 had forms of severe combined immunodeficiency, eight had inborn metabolism errors, seven had leukemia, six had other forms of immunodeficiency diseases, two were diagnosed with neuroblastoma, two had non-malignant hematological disorders, and one each had a germ cell tumor, an undefined tumor, and a marrow stem cell deficit. All the children were treated at UCSF from 1986 to 2003.

The researchers tested the children before undergoing the bone marrow transplantation and after an average of 14.5 months post-therapy. The researchers used the validated Vineland Adaptive Behavior Scales and Bayley Scales of Infant Development. Data were analyzed using multiple regression analyses.

On the Vineland scale domains:

* Communication skills declined from a mean of 99.09 to 90.25, a medium to large effect (P<0.001).
* Socialization skills declined from a mean of 100.44 to 94.56, a medium effect (P=0.001).
* Daily living skills declined from a mean of 97.95 to 90.63, a medium effect (P=0.001).
* Motor skills declined from a mean of 92.38 to 89.98, a nonsignificant effect (P=0.175).

On the Bayley scales:

* Mental development index declined from a mean of 94.95 to 88.82, a nonsignificant effect (P=0.062).
* Psychomotor development skills declined from a mean of 82.44 to 78.75, a nonsignificant effect (P=0.381).

“The process of bone marrow transplantation usually involves a long period of compromised immunity and potential neurotoxic procedures,” Dr. Ruthruff noted. “The infant is kept in medical isolation at the hospital for periods ranging from a few days to six or more months. When the infant returns home, isolation and social restrictions continue for a period lasting from a few months to a year. Sanitation and prevention of the introduction of germs into the home environment severely curtail the infant’s and family’s activities.”

“Many infants are exposed to high-dose ablative chemotherapies and/or total body radiation to prepare their body for the new bone marrow. Some were previously exposed to multiple courses of chemotherapy. Some are given agents to prevent and/or treat graft-versus-host disease.”

The results of this study are not surprising,” said Jacqueline Lefkowitz, LCSW, a master social work clinician at New York Presbyterian Hospital-Weill Cornell Medical College. “Events occurring in the earliest stage of life play a crucial role in the cognitive and emotional development of children.”

Lefkowitz said that cancer and cancer treatments are often traumatic. “Traumatic experiences strongly influence psychosocial development,” she added. “However, all experiences are mediated by the parents or the primary attachment figures.”

She recommended further studies into “whether parents’ coping styles influence the interactions with their child and whether, in turn, these interactions also play a significant role in the child’s growth and development.”

linkback url: http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/6496


Fund set up to help family of Naples baby in need of emergency transplant

August 24, 2007

Fund set up to help family of Naples baby in need of emergency transplant

Friday, August 24, 2007

A Naples baby recently diagnosed with a severe immune deficiency needs an emergency bone marrow transplant and his parents need help with out-of-pocket medical expenses.

Adam Saada, 3 months, has been diagnosed with Severe Combined Immunodeficiency, SCID, and is presently hospitalized and quarantined at Joe DiMaggio Children’s Hospital in Hollywood. He is being moved shortly to Jackson Memorial Hospital to a different quarantine unit, said Sue Buck, the baby’s great aunt. The baby’s parents are Amy and Hussam Saada, of Naples.

The immune system deficiency is the same rare disorder that became well known in the 1970’s as the “Bubble Boy” disease,” involving David Vetter, who had SCID and lived in a plastic germ-free bubble for 12 years.

The disease was once considered fatal but is now seen as a pediatric emergency and can be remedied by a bone marrow transplant. The first successful bone marrow transplant was performed in 1968. More recently, gene therapy has become possible but also carries risks.

Amy Saada works for Collier County’s Department of Human Services and her husband is employed at Wachovia Bank. While the family has insurance, they will face major expenses out of pocket, Buck said.

A trust account has been set up at a local bank for donations.

Adam was born on April 3 and was fine but three weeks ago he became sick and was taken to North Naples Hospital, where he was diagnosed with PCP pneumonia, a certain strain of pneumonia, and he was flown to Joe DiMaggio.

“Two days ago, they figured out he has no immune system,” Buck said.

The bone marrow transplant is urgent because it’s unclear how long he can be quarantined and fighting the pneumonia with no immune system, she said. Infectious complications are a major threat to effective treatment for SCID, according to the U.S. Centers for Disease Control.

The CDC estimates one incident for every 100,000 live births.

“They take out his marrow and put in new marrow and he ends up with a new immune system when it is done,” Buck said. “It does not have to be a perfect match.”

A trust account has been established with a family friend, Sharon Ardrey, to accept donations to help with the family’s medical expenses.

Checks should be made out to “Sharon Ardrey trust for Adam Saada” and mailed to Ardrey at 1507 Vintage Lane, Naples, FL 34104, or send a check in the same name to Encore Bank, 3003 Tamiami Trail, Naples, FL 34103.

linkback url: http://www.naplesnews.com/news/2007/aug/24/fund_set_help_family_naples_baby_need_emergency_tr/
?breaking_news


Baxter to Launch GARDian(TM), a Groundbreaking Initiative That Helps Provide Continued Access to GAMMAGARD for Current Patients

August 22, 2007

Baxter to Launch GARDian(TM), a Groundbreaking Initiative That Helps Provide Continued Access to GAMMAGARD for Current Patients

Aug 22, 2007 9:00 PM (1 day ago)
DEERFIELD, Ill., Aug. 22 – Baxter International Inc. (NYSE: BAX) today announced that it will launch GARDian, an innovative program that helps provide continued access for patients relying on GAMMAGARD LIQUID and GAMMAGARD S/D [Immune Globulin Intravenous (Human)] (IGIV). IGIV products like GAMMAGARD LIQUID and GAMMAGARD S/D are immunoglobulin (IgG) replacement therapies containing broad-spectrum immunoglobulins and are indicated for patients with primary immunodeficiency. Primary immunodeficiency is a group of genetic disorders in which the immune system fails to produce adequate amounts of antibodies, thereby predisposing individuals to increased risk of infection.

IGIV users and physicians can experience changes involving their providers or site of care that can sometimes impede access to their preferred IGIV therapy. Baxter’s GARDian program, which is expected to start early next year, will provide patients and physicians with continued access to GAMMAGARD LIQUID and GAMMAGARD S/D even when such changes occur.

GARDian is viewed as a logical extension of other successful patient- centric programs pioneered by Baxter. The hallmark of each of these programs is continued access to GAMMAGARD LIQUID and GAMMAGARD S/D. They include:

— GAMMAssist — An innovative program that allows eligible users of
GAMMAGARD to continue to receive their immunoglobulin therapy in the
event of a lapse in insurance.
— Low IgA/Brand Intolerance Program — A program providing patient access
to GAMMAGARD S/D selected for its lower content of certain
immunoglobulins called IgA, for certain patients experiencing adverse
reactions from other IGIV therapies.
— GAMMAGARD LIQUID and GAMMAGARD S/D Portability – Launched in late 2006,
this program is designed to provide hospitals with continued access to
GAMMAGARD irrespective of changes to their group purchasing
organization affiliation.

Patient organizations welcomed the announcement of Baxter’s newest patient access innovation. “Access to the IGIV product prescribed by their physician is extremely important for PI patients,” said Marcia Boyle, founder and president of the Immune Deficiency Foundation, a national nonprofit patient organization dedicated to improving the diagnosis and treatment of primary immunodeficiency diseases through research, education and advocacy. “Baxter’s program will be extremely helpful to PI patients by reassuring that they will not have to change from their product of choice.” Noting the success of Baxter’s other patient centric initiatives, Ms. Boyle added, “We would love to see such a program developed for all of the patients in our community who use GAMMAGARD LIQUID and GAMMAGARD S/D.”

“Baxter has been a pioneer in advancing the science of IGIV, and its intent to establish a program that maintains continuity in IGIV therapy at the patient level is an important innovation in the industry — one that is sure to be embraced by PID patients who use GAMMAGARD LIQUID and GAMMAGARD S/D,” added Fred Modell, co-founder of the Jeffrey Modell Foundation, a national nonprofit organization dedicated to early and precise diagnosis, meaningful treatment and ultimately cures of PID.

Baxter’s GARDian Program

Baxter plans to launch a pilot of GARDian in early 2008. The pilot initiative and the ensuing program will be open to current patients in the United States that routinely use the product as prescribed by a physician. Using a simple, voluntary enrollment process administered through patients’ healthcare providers, enrollees will have the comfort that GAMMAGARD LIQUID and GAMMAGARD S/D is available to them even if they experience changes involving their providers or site of care. A third party vendor will manage the program, and Baxter will not have access to patient data.

Enrollment in this program will be voluntary and will not automatically preclude those patients not participating in the program from accessing GAMMAGARD LIQUID and GAMMAGARD S/D. Baxter will continue to work closely with patient organizations and key thought leaders from different clinical specialties that prescribe IGIV therapy to launch the program. Patients not enrolling in the voluntary GARDian program will still be eligible for other GAMMAGARD patient programs (e.g. GAMMAssist and the Low IgA/Brand Intolerance Program and product Portability programs).

“Baxter has a long, proud history of advancing the science of IGIV therapy and serving the patients who rely on our IGIV therapies,” said Larry Guiheen, president, Baxter Biopharmaceuticals, North America. “Baxter is committed to providing continued access to their therapy of choice for our patients. The GARDian program represents our continued commitment to that goal.”

Patients and physicians can sign up to receive more information about the GARDian program at http://www.immunedisease.com.

About GAMMAGARD LIQUID 10%

GAMMAGARD LIQUID is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. These include but are not limited to congenital X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

About GAMMAGARD S/D

GAMMAGARD S/D is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. These include but are not limited to congenital X linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

GAMMAGARD S/D must not be used in patients with selective IgA deficiency (IgA, 0.05 g/L) where the IgA deficiency is the only abnormality of concern.

About GAMMAGARD S/D with IgA < 1 microgram/mL in a 5% solution

GAMMAGARD S/D is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. These include but are not limited to congenital X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

GAMMAGARD S/D must not be used in patients with selective IgA deficiency (IgA < 0.05 g/L) where the IgA deficiency is the only abnormality of concern.

About Primary Immunodeficiency Disorders

Primary immunodeficiency disorders encompass more than 100 diseases caused by an immune system that does not function correctly. According to the Immune Deficiency Foundation, approximately 50,000 persons in the United States have one of the primary immunodeficiency disorders. For many people with primary immunodeficiency, the cause is a lack of antibodies. IGIV therapy can help restore IgG levels to near normal, helping the immune system function properly and prevent infections or fight them when they occur.

Important Safety Information

GAMMAGARD LIQUID

GAMMAGARD LIQUID is contraindicated in patients with known anaphylactic or severe hypersensitivity responses to Immune Globulin (Human). Patients with severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction.

Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. Glycine, an amino acid, is used as a stabilizer. GAMMAGARD LIQUID does not contain sucrose.

GAMMAGARD LIQUID is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Components used in the packaging of this product are latex-free.

Thrombotic events have been reported in association with IGIV. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity, hypercoagulable disorders, and prolonged periods of immobilization.

IGIV products can contain blood group antibodies that may cause a positive direct antiglobulin reaction and, rarely, hemolysis.

Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.

Various mild and moderate reactions, such as headache, fever, fatigue, chills, flushing, dizziness, urticaria, wheezing or chest tightness, nausea, vomiting, rigors, back pain, chest pain, muscle cramps, and changes in blood pressure may occur with infusions of Immune Globulin Intravenous (Human).

GAMMAGARD S/D

Patients may experience severe hypersensitivity reactions or anaphylaxis in the setting of detectable IgA levels following infusion of GAMMAGARD S/D.

Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. GAMMAGARD S/D does not contain sucrose.

GAMMAGARD S/D is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.

Certain components used in the packaging of GAMMAGARD S/D contain natural rubber latex.

IGIV products can contain blood group antibodies that may cause a positive direct antiglobulin reaction and, rarely, hemolysis.

Thrombotic events have been reported in association with IGIV. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity, hypercoagulable disorders, and prolonged periods of immobilization.

Various minor reactions, such as mild to moderate hypotension, headache, fatigue, chills, backache, leg cramps, lightheadedness, fever, urticaria, flushing, slight elevation of blood pressure, nausea and vomiting, may occasionally occur.

GAMMAGARD S/D with IgA < 1 microgram/mL in a 5% solution

Patients may experience severe hypersensitivity reactions or anaphylaxis in the setting of detectable IgA levels following infusion of GAMMAGARD S/D.

Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number.

GAMMAGARD S/D does not contain sucrose.

GAMMAGARD S/D, IgA <1 microgram/mL, has a lower IgA concentration than GAMMAGARD S/D which has a concentration of 1 to 2.2 microgram/mL. IGIV preparations depleted of IgA (0.4 to 2.9 microgram/mL) were shown to be better tolerated by a limited number of patients who reacted to IGIV preparations with higher IgA concentrations. However, the concentration of IgA that will not provoke a reaction is not known, and therefore all IGIV preparations carry the risk of inducing an anaphylactic reaction to IgA. In such instances, a risk of anaphylaxis may exist despite the fact that GAMMAGARD S/D, IgA <1 microgram/mL, contains trace amounts of IgA.

GAMMAGARD S/D is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.

Certain components used in the packaging of GAMMAGARD S/D contain natural rubber latex.

IGIV products can contain blood group antibodies that may cause a positive direct antiglobulin reaction and, rarely, hemolysis.

Thrombotic events have been reported in association with IGIV. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity, hypercoagulable disorders, and prolonged periods of immobilization.

Various minor reactions, such as mild to moderate hypotension, headache, fatigue, chills, backache, leg cramps, lightheadedness, fever, urticaria, flushing, slight elevation of blood pressure, nausea and vomiting may occasionally occur.

The potential risks and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom IGIV administration is being considered.

For full prescribing information for GAMMAGARD LIQUID, GAMMAGARD S/D and GAMMAGARD S/D with IgA less than 1 microgram/mL in a 5% solution please go to: http://www.baxter.com/products/biopharmaceuticals/downloads/gammagard_us_pi.pd f (To link to this website, please copy and paste URL in Internet browser) http://www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_PI.pdf http://www.immunedisease.com/US/pdfs/gammagardsd_iga.pdf

About Baxter

Baxter International Inc., through its subsidiaries, assists healthcare professionals and their patients with the treatment of complex medical conditions, including hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other conditions. The company applies its expertise in medical devices, pharmaceuticals and biotechnology to make a meaningful difference in patients’ lives.

SOURCE Baxter International Inc.

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_a_Groundbreaking_Initiative_That_Helps_Provide_Continued_Access_to_GAMMAGARD
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Risky Business

August 21, 2007

Risky business
It’s not the technology of gene therapy but the regulation of clinical trials that we should be most afraid of, says Apoorva Mandavilli.
Column
Published online: 21 August 2007; | doi:10.1038/news070820-1

Risky business
It’s not the technology of gene therapy but the regulation of clinical trials that we should be most afraid of, says Apoorva Mandavilli.

Apoorva Mandavilli
Almost exactly seven years after the first death in a gene-therapy trial, another unexpected death hit the field late last month – followed quickly by panic, outrage and some calls for an end to gene therapy altogether.

But to blame and ban all gene therapy because of this would be rash and misguided. And it might risk missing the point. What we should be most outraged and scared by is the way this trial took place — and the similar mis-steps that seem to accompany a vast number of clinical trials, gene therapy or no gene therapy.

On 2 July Jolee Mohr, a 36-year-old woman in Chicago, received an injection she thought would treat her painful — although not debilitating — arthritis. She died on 24 July of multiple organ failure, which was also the cause of death of 18-year-old Jesse Gelsinger in September 1999. In each case, the US Food and Drug Administration responded by suspending the trial and any others that used a similar approach.

But tragic and avoidable as both deaths were, I think we should be more worried about a broken system for clinical trials than of a risky treatment.

Short on science

Gene therapy is an experimental procedure in which an ostensibly harmless virus is used to replace faulty genes in an individual’s body with healthy ones. I say ‘ostensibly’ because Mohr’s treatment involved adeno-associated virus (AAV), which has never caused any problems in humans. But the full cause of Mohr’s death is still unknown and may well be because of the AAV vector.

Here’s what we know about what may have gone wrong: at the time of her death, Mohr’s entire body was fighting a fungal and a cold-sore-virus infection, both of which normally cause only mild symptoms. Mohr’s response to the infections suggests that her immune system, which the gene therapy was supposed to suppress only in her knees, may have been shattered throughout her body.

But Mohr was also taking a drug called Humira, which is known to increase the risk of the fungal infection. We also know that since the trial began in October 2005, more than 70 other people have received the gene-therapy treatment with no ill effects.

At this point, that is about all we know about the science — not enough, by a long shot, to pin the entire blame on gene therapy.

Scary stuff

There’s a lot more we do know about the clinical-trial procedures, and some of these details seem far more frightening to me than any jab.

The federal panel that reviewed the trial, run by Seattle-based Targeted Genetics, questioned the need for gene therapy for a non-life-threatening illness such as arthritis, and expressed concerns about the treatment’s potential effects on the immune system. But the advice given by such panels isn’t legally binding — companies can do what they like with such input.

Mohr was a participant in only an early stage of the clinical trial, designed to test the safety, not effectiveness, of the treatment. But according to Mohr’s husband, she was under the impression that it might help to ease her arthritis.

Mohr’s rheumatologist, who signed her up for the treatment, was being paid by the company to recruit patients into the trial. Experts say that shouldn’t happen; a patient might not listen as closely to a description of risks if advice comes from their own doctor as opposed to a third party.

The rheumatologist and the company say that the risks were clearly explained to Mohr. But it’s worth noting that she signed Targeted Genetics’ informed consent document in the office, instead of taking it home to read carefully, as most clinical-trial protocols require. It was more than 10 pages long, with the disclaimer warning of the risk of death buried deep inside.

Not alone

Every one of these potential problems is of grave concern. But the sad truth is that none is unique to gene therapy, or even very surprising.

It seems to me that conflict of interest, of inadequate informed consent, and shoddy reporting of ‘adverse events’ are endemic to the entire system of clinical trials. For a hit-list of potential problems, just take a look at scandals in recent years over the safety of antidepressants, the painkiller Vioxx and the diabetes drug Avandia. A 2003 review of 37 studies found that one of every four researchers has links to the industry and that industry-financed research is more likely to come to conclusions that are favourable to companies1.

This latest tragedy should serve as a warning and should bring about reform in the system.

Gene therapy has had some successes, albeit modest. A few trials, notably for ‘bubble boy disease’ and Parkinson’s disease, have shown promise.

On 17 September, the National Institutes of Health’s advisory committee on gene therapy will take a hard look at all the evidence in the Mohr case. Mohr’s husband, who plans to attend the hearing, says that until her death has been proven to be a result of the gene therapy, he doesn’t want to lay any blame because, he explains, the approach has the potential to help many people.

If he can be so reasonable, surely so can we.

linkback url: http://www.nature.com/news/2007/070820/full/070820-1.html


Upcoming Immune Deficiency Foundation Local Area Meetings for Patients and Their Families

August 20, 2007

Upcoming Immune Deficiency Foundation Local Area Meetings for Patients and Their Families

  • August 19, 2007 IDF Day at the Mariners Ellis Pavilion at Safeco FieldSeattle, WA, Education Program -11:00 a.m. to 12:00 p.m.Lunch – 12:00 p.m. to 1:00 p.m. Mariners vs. Chicago White Sox – 1:05 p.m.$5 includes educational program, lunch and game. For more information contact Joanne Pease at 206.244.2248 or email peezpod@aol.com   
  • September 8, 2007 Patient Education MeetingHoagland Pincus Conference CenterShrewsbury, MA, For more information contact Towma Rastad at 508.596.3746 or email allissalec@yahoo.com  
  • September 15, 2007 IDF Center of Excellence Patient Education Meeting, Duke University Medical Center, Searle Center, Room E Saturday, September 15, 2007 9:00 a.m. to 2:30 p.m.Speakers:  Rebecca Buckley, MD, Laurie Lee, MD and Joseph Roberts, MD, PhD., For more information, contact Diana Gill at 443.632.2545 or email dgill@primaryimmune.org                                  
  • September 15, 2007 Patient Education Meeting Milwaukee County Zoo Milwaukee, WI, Time: TBA For more information contact Linda Keegan at lindakeeganwi@aol.com.

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