NIH funds Center of Excellence for Molecular Hematology at Cincinnati Children’s

October 7, 2010

NIH funds Center of Excellence for Molecular Hematology at Cincinnati Children’s

CINCINNATI – Cincinnati Children’s Hospital Medical Center has been named one of five national Centers of Excellence for Molecular Hematology to find new gene and cell therapies for inherited diseases affecting blood cells.

The National Institute of Diabetes, Digestive and Kidney Diseases, one of 19 National Institutes of Health, has approved a five-year, $3.4 million grant for Cincinnati Children’s to establish the multi-disciplinary center. The center blends Cincinnati Children’s extensive research and clinical expertise, including its close collaboration with research affiliate, the University of Cincinnati College of Medicine.

A key aim of the Cincinnati Center for Molecular Hematology is to accelerate the discovery of new therapeutic approaches for conditions like sickle cell anemia, thalessemia, leukemia, immunological disorders and other blood cell-based diseases, according to Yi Zheng, Ph.D., director of Experimental Hematology and Cancer Biology and director of the new center. The center will also help speed the transition of new therapies from the research laboratory to clinical trials.

“We have a strong basic research pipeline at Cincinnati Children’s and the ability to rapidly translate basic research into the clinic,” Dr. Zheng said. “The medical center is one of the few institutions in the country that can claim excellence in basic science, expertise in genetic manipulation under Good Manufacturing Practice conditions, and also provide outstanding cell and gene therapies and patient care at a single location.”

The challenge is to understand and correct diseases caused by interactions between mutated genes and environmental factors that adversely affect blood cells. Researchers believe that successfully applying molecular and cell therapeutics to blood cells that can be transplanted into patients will provide life-long cures for inherited diseases.

Cincinnati Children’s is already working on gene therapy trials for new treatments of sickle cell anemia, X-SCID (X-linked severe combined immunodeficiency), solid cancers such as rhabdomyosarcoma and Ewing’s sarcoma, and a number of other diseases.

The NIDDK grant helps fund four research cores that support the research activities of multiple investigators. The cores are vital to the rapid and efficient translation of original discoveries from the laboratory to the clinic, Dr. Zheng said

The research cores supported by the grant are:

* The Translational Core. The core includes 10,000-square-feet of tightly controlled “clean room” laboratory space. The facility can manipulate human cells outside of the body to create cell products for therapeutic use in specific diseases. It also produces viral vectors to allow the delivery of specific genetic information for treating disease
* The Genomics and Genetics Core. The core provides leading edge genomic analysis of blood cell diseases and determining the normal genetic traits of blood stem and progenitor (early stage) cells.
* The Mouse Xenotransplant/Transgenic Core. The core maintains specialized mouse strains and provides mouse transplant and transgenic services that allow scientists to study mouse models of human disease.
* The Flow Cytometry Core. This laboratory allows scientists to analyze and sort different types of blood cells.

The center designation comes after years of basic science discoveries in genetics and genomics have put researchers on the threshold of exciting new therapeutic approaches for blood cell disorders, according to Arnold Strauss, M.D., director of the Cincinnati Children’s Research Foundation, chief medical director of the medical center, and chair of pediatrics at the UC College of Medicine.

“We are on the verge of being able to use novel interventions to treat and really cure disorders, such as sickle cell anemia, that severely impair normal lives for children and adolescents and cause premature death in young adults,” Dr. Strauss said. “After 40 years of watching afflicted children suffer and die, I am incredibly excited that the time is arriving for their cure.”

Helping secure the center of excellence designation is a decade of rapid growth in Cincinnati Children’s research activities and in its reputation. The medical center is the nation’s second largest pediatric research organization as measured by NIH funding, which totaled over $115 million in fiscal 2009 – an increase from $12.3 million just a decade ago. The medical center currently has 950,000 square feet of research laboratory space, with plans underway for an additional 300,000 square feet.

The expansion has included establishment of nearly two dozen research cores, with capabilities ranging from creating and maintaining stem cell lines to one of the largest academic bioinformatics and computing centers in the nation.

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MSD’s Vaccine, ROTATEQ®, Reduced Severe Rotavirus Gastroenteritis in Infants in Asia and Africa

August 6, 2010

MSD’s Vaccine, ROTATEQ®, Reduced Severe Rotavirus Gastroenteritis in Infants in Asia and Africa

2010-08-06 01:23:02 –

In a study published today in The Lancet, ROTATEQ® (rotavirus vaccine, live, oral, pentavalent), MSD’s rotavirus vaccine, reduced the number of cases of severe rotavirus gastroenteritis by nearly half (48 percent) in infants evaluated in developing countries in Asia (Bangladesh and Vietnam) and by 39 percent in infants evaluated in developing countries in Africa (Ghana, Kenya, and Mali) through nearly two years of follow-up. This is the first study demonstrating efficacy for any rotavirus vaccine in developing countries in Asia and the first study to show efficacy for ROTATEQ in developing countries of Asia and Africa.

“We are encouraged by the data,” said study investigator Dr. Khalequz Zaman, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. “In this study, ROTATEQ prevented severe rotavirus gastroenteritis in infants in regions in Africa and Asia where the disease burden is quite high and rotavirus vaccines are needed the most.”

ROTATEQ is an oral pentavalent vaccine indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the serotypes G1, G2, G3, G4, and G-serotypes that contain P1A[8] (e.g., G9). ROTATEQ may be administered as early as 6 weeks of age. The first dose should be administered at 6 to 12 weeks of age, with the subsequent doses administered at a minimum interval of four weeks between each dose.

ROTATEQ should not be administered to infants with a demonstrated history of hypersensitivity to any component of the vaccine. Infants with Severe Combined Immunodeficiency Disease (SCID) should not receive ROTATEQ. Cases of gastroenteritis associated with vaccine virus have been reported post-marketing in infants with SCID.

Rotavirus gastroenteritis is the leading cause of diarrheal disease mortality among children under 5 years of age, resulting in an estimated 527,000 deaths per year globally, mostly in Asia and Africa. It is highly prevalent and highly contagious, infecting nearly all children by age 5, often more than once in both developed and developing countries.

“Given the impact of rotavirus gastroenteritis in the developing world, reduction in severe rotavirus disease represents a critically important public health goal,” said Mark Feinberg, M.D., Ph.D., vice president, Medical Affairs and Policy, Merck Vaccines. “Merck is committed to advancing global health by improving access to ROTATEQ in areas most affected by the severe consequences of rotavirus disease.”

In 2009, the World Health Organization’s (WHO) Strategic Advisory Group of Experts recommended to expand rotavirus vaccine use to all regions of the world. The efficacy data for ROTATEQ in Asia and Africa, along with effectiveness data in Nicaragua, helped inform the WHO’s recommendation for expansion of the rotavirus vaccine to all regions. This recommendation led to global WHO-pre-qualification of ROTATEQ, accelerating the availability of vaccines in the developing world.

About the Study

More than 7,500 infants between 4 and 12 weeks of age from five developing countries in Asia (Bangladesh and Vietnam) and Africa (Ghana, Kenya, and Mali) were enrolled in the two-year randomized, double-blind, placebo-controlled clinical trial. The trial was designed to evaluate the efficacy of three doses of ROTATEQ (n=3,751) against severe rotavirus gastroenteritis versus placebo (n=3,753) in low income countries with high incidence of diarrheal disease mortality.

The study was coordinated through a partnership between Merck and the Rotavirus Vaccine Program (RVP), a collaboration between PATH, an international non-profit organization, WHO and the U.S. Centers for Disease Control and Prevention. Clinical trial investigators in Asia and Africa partnered with Merck and RVP to conduct the trial. The Merck and RVP partnership was initiated by the GAVI Alliance in an effort to introduce rotavirus vaccine in the developing world. The study was funded by RVP with a grant from the GAVI Alliance and was co-sponsored by Merck.

In this study, infants received ROTATEQ or placebo at approximately 6, 10, and 14 weeks of age with routine infant vaccines. Infants between 4 and 12 weeks of age who were free of symptoms of active gastrointestinal disease and could be adequately followed for safety were eligible. The primary endpoint was rotavirus gastroenteritis, irrespective of serotype, occurring 14 days or more after the third dose of ROTATEQ or placebo until the end of the study. Gastroenteritis was defined as three or more watery or looser than normal stools within a 24 hour period or forceful vomiting. Severity of rotavirus gastroenteritis was defined by a 20 point clinical scoring system (modified Vesikari system), with those cases with a score of 11 or more being classified as severe.

In Asia, 1,018 infants were randomly assigned to receive ROTATEQ and 1,018 infants received placebo; median follow-up time in both groups, from 14 days after the third dose of vaccine or placebo until final disposition, was 498 days. Over the entire study period, there were 38 cases of severe rotavirus gastroenteritis in the vaccine group, compared with 71 cases reported in the placebo group, resulting in a vaccine efficacy of 48.3 percent (95 percent CI 22.3, 66.1 percent) at sites in Asia. Through nearly two years of follow up, vaccine efficacy was 42.7 percent (95 percent CI 10.4, 63.9 percent) in Bangladesh and 63.9 percent (95 percent CI 7.6, 90.9 percent) in Vietnam.

In Africa, 2,733 infants were randomly assigned to receive ROTATEQ and 2,735 infants received placebo; median follow-up time in both groups was 527 days starting 14 days after the third dose of vaccine or placebo.
Over the entire study period, there were 79 cases of severe rotavirus gastroenteritis reported in the vaccine group, compared with the 129 cases reported in the placebo group, resulting in a vaccine efficacy of 39.3 percent (95 percent CI 19.1, 54.7 percent) at sites in Africa.

Efficacy was 55.5 percent (95 percent CI 28.0, 73.1 percent) in Ghana, 63.9 percent (95 percent CI < 0, 89.8 percent) in Kenya, and 17.6 percent (95 percent CI < 0, 45.0 percent) in Mali through nearly two years of follow up.

In post-hoc analyses, overall efficacy against severe rotavirus gastroenteritis in Asian infants was 51 percent (95 percent CI 12.8, 73.3 percent) in the first year of life and 45.5 percent (95 percent CI 1.2, 70.7 percent) in the second year of life. Efficacy in Bangladesh was 45.7 percent (95 percent CI < 0, 71.8 percent) in the first year of life and 39.3 percent (95 percent CI < 0, 69.7 percent) in the second year of life. Efficacy in Vietnam was 72.3 percent (95 percent CI < 0, 97.2 percent) in the first year of life and 64.6 percent (95 percent CI < 0, 93.9 percent) in the second year of life.

Overall efficacy against severe rotavirus gastroenteritis in African infants was 64.2 percent (95 percent CI 40.2, 79.4 percent) in the first year of life and 19.6 percent (95 percent CI < 0, 44.4 percent) in the second year of life. Efficacy in Ghana was 65.0 percent (95 percent CI 35.5, 81.9 percent) in the first year of life and 29.4 percent (95 percent CI < 0, 70.7 percent) in the second year of life. Efficacy in Kenya was 83.4 percent (95 percent CI 25.5, 98.2 percent) in the first year of life and less than 0 percent (95 percent CI < 0, 82.3 percent) in the second year of life. Efficacy in Mali was 1.0 percent (95 percent CI < 0, 81.6 percent) in the first year of life and 19.2 percent (95 percent CI < 0, 47.3 percent) in the second year of life. The surveillance system in the study protocol was designed to detect participants presenting to healthcare facilities. However, in Mali, for cultural reasons, many cases of severe diarrhea were preferentially taken to traditional healers during the first year of the study. Strengthening of the surveillance system after the first year of the study resulted in a 12-fold increase in detection of severe rotavirus gastroenteritis in Mali in the second year of life, and a higher point estimate of efficacy in the second year than in the first year. The proportion of subjects with reported serious adverse events (SAEs) was comparable between the vaccine and placebo groups in Asia (2.5 percent in ROTATEQ group, 2.0 percent in placebo group) and Africa (1.5 percent in ROTATEQ group, 1.7 percent in placebo group). The most frequent serious adverse event was pneumonia in Asia (1.2 percent in ROTATEQ group, 1.5 percent in placebo group) and gastroenteritis in Africa (0.6 percent in either ROTATEQ or placebo group). One confirmed case of intussusception (in Vietnam), in the placebo group (at Day 97 post-Dose 3), was reported during the clinical trial. “This study provided insights into how vaccine immune responses and efficacy varied in developing countries,” said Max Ciarlet, Ph.D., associate director, Merck Research Laboratories. “Several factors may adversely affect immune response and efficacy of vaccines in these regions, including poor nutrition, the presence of other intestinal bacteria and viruses, and co-infections in the digestive system.” Select Safety Information about ROTATEQ No safety or efficacy data are available from clinical trials regarding the administration of ROTATEQ to immunocompromised patients such as individuals with malignancies or who are otherwise immunocompromised; individuals receiving immunosuppressive therapy; individuals infected with HIV; or individuals who received a blood transfusion or blood products, including immunoglobulins within 42 days. More than 71,000 infants were evaluated in three Phase 3, placebo-controlled clinical trials. Parents/guardians were contacted on days 7, 14, and 42 after each dose regarding intussusception and any other serious adverse events. In the Rotavirus Efficacy and Safety Trial (REST) of more than 69,000 infants, ROTATEQ did not increase the risk of intussusception relative to placebo. There were no confirmed cases of intussesception during the 42-day period after dose one and no clustering of cases among vaccine recipients at any time period after any dose. Four cases of intussusception were reported in children who had received placebo following the one-year safety follow-up period. In a subset of more than 11,000 infants in these trials, the presence of adverse events was reported for 42 days after each dose. The most commonly reported adverse experiences with ROTATEQ (frequency >1/10) include upper respiratory infection, diarrhea, vomiting, pyrexia, otitis media, irritability, and cough.

The following adverse experiences have been spontaneously reported during post-approval use of ROTATEQ: urticaria and gastroenteritis with vaccine viral shedding in infants with SCID. Because these experiences were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish a causal relationship to vaccine exposure.

In a prospective post-marketing observational study conducted using a large medical claims database, the risks of intussusception or Kawasaki disease resulting in emergency department visits or hospitalizations during the 30 days following any dose of vaccine were analyzed among 85,150 infants receiving one or more doses of ROTATEQ.

During the 0-30 day follow-up period after vaccination, there were no statistically significant differences in the rates of intussusception or Kawasaki disease compared with the expected background rates. In addition, there was no statistically significant increased risk of these adverse events during the 0-30 day follow-up period when comparing the 17,433 person-years of follow-up among infants receiving ROTATEQ (n equals 85,150) with the 12,339 person-years of follow up among a concurrent control group of infants who received DTaP, but not ROTATEQ (n equals 62,617).

There were six confirmed cases of intussusception among infants vaccinated with ROTATEQ compared with five among the concurrent controls vaccinated with DTaP (relative risk equals 0.8, 95 percent CI 0.22-3.52). There was one chart-confirmed case of Kawasaki disease identified among infants vaccinated with ROTATEQ and one chart-confirmed case of Kawasaki disease among concurrent DTaP controls (relative risk equals 0.7, 95 percent CI 0.01-55.56). In the general safety analyses, the Safety Monitoring Committee did not identify any specific safety concerns.

ROTATEQ® is a registered trademark of Merck & Co. Inc., Whitehouse Station, N.J., USA

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New Gene Therapy Trials To Test Cure For Bubble Boy Syndrome

July 22, 2010

New Gene Therapy Trials To Test Cure For Bubble Boy Syndrome

New research sponsored at Children’s Hospital Boston will use gene therapy to fix the malfunctioning DNA of children with severe combined immunodeficiency (SCID), popularly known as the bubble boy syndrome. SCID cripples the immune systems of children with the disorder, leaving their bodies open to fatal infections. Bone marrow transplants have shown great success in treating SCID, but they are difficult to perform and unless they have a fully matched sibling, patients can wait years for an appropriate donor. Now a new wave of gene therapy is about to begin trials, sidestepping the transplant issues altogether by reprogramming a patient’s immune system to function properly.

Last year we covered gene therapy that cures the second most common subtype of the disease, SCID-ADA. The new study, sponsored by Dr. David Williams at Children’s, just got a green light from the FDA and is currently accepting patients. The research will apply a newly developed gene therapy retrovirus to the most common form of the disease: X-SCID, which involves a mutation along the IL2RG gene on the X chromosome. The gene therapy involves taking the patient’s own bone marrow, upgrading the cell’s DNA with a functional version of the gene, and reintroducing the altered marrow.

SCID is an immunodeficiency disorder that results from a child having a defective version of one of several genes essential to producing lymphocytes (white blood cells). Without a functional immune system, the child is highly susceptible to viral and bacterial infection – without treatment, most children die within the first year of life. Sterile isolation (the infamous bubble) is necessary unless the disease can be treated in some way. Traditionally, SCID has been treated with a bone marrow transplant from a sibling or parent if one is a suitable match; if not, children often wait for years for a donation.

Approximately 1 in every 100,000 children born suffer from SCID. The disease can be caused by mutations along one of several genes, and these mutations are not always easy to screen for. Often, SCID is not diagnosed until several months after birth, once the mother’s antibodies are cleared from the body and the baby begins to develop recurring infections. Because X-SCID is due to a mutation along the X chromosome, female carriers are generally heterozygous and do not express the disease. Only males develop X-SCID.

Bone marrow transplants have been highly successful in treating SCID, especially when they are administered early in life. Ideally, a transplant would come from a full-match sibling; because not every patient has one, sometimes unmatched siblings or parents donate marrow. These transplants require drug treatments to prevent graft-versus-host disease, and are riskier to perform in infants. Transplanted cells usually do not produce antibodies, and so transplant patients require immunoglobulin injections for the rest of their lives. These complications make marrow transplants a frustrating treatment option for many families.

SCID gene therapy, step-by-step

This is where gene therapy comes in. Rather than replace a patient’s faulty marrow with someone else’s, gene therapy reprograms the patient’s own genome by inserting new DNA to fix broken genes. First, bone marrow samples are taken from the patient. Next, a vector (e.g. a virus or retrovirus) is used to insert DNA into the marrow cells; this genetic material binds with the patient’s own, upgrading their genome to include the missing gene. Finally, the marrow is reinserted into the patient, where it can generate the lymphocytes that SCID patients lack. There is no risk of graft rejection with a patient’s own cells, and there is no need to wait for an acceptable donor. Antibodies can even be produced by the upgraded cells, eliminating the need for immunoglobulin injections.

One risk of gene therapy is that the DNA is often inserted randomly into the patient’s own genome. If the added DNA is inserted into the middle of an important gene – say, a gene that normally controls cell division – it can disrupt that gene’s function and result in cancer. Gene therapy for X-SCID has been controversial since 2005, when five children in Europe got leukemia from the retrovirus used in experimental treatments.

Since then, the Transatlantic Gene Therapy Consortium – an international collaboration between multiple institutions – set about completely redesigning the vector used to upgrade the patient’s genome. The retrovirus used in the current study is the first X-SCID treatment to be approved by the FDA since 2005, and underwent extensive regulatory review prior to approval. Researchers are looking for twenty subjects to undergo a one-time treatment; the children will be monitored for leukemia for fifteen years following the initial gene therapy.

Though it is a rare disease, SCID entered the cultural consciousness in the 1970’s and 80’s through extensive media coverage of David Vetter, dubbed “the boy in the plastic bubble.” Vetter died in 1984 following an unmatched bone marrow transplant from his sister, a transplant which inadvertently infected David with the Epstein-Barr virus.

The Consortium is an international collaboration that includes researchers from Children’s Hospital Boston, Hannover Medical School (Germany), and Institute of Child Health (London). Information on subject recruitment can be found here.

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CDC: SCID is Contraindication for Rotavirus Vaccine

June 10, 2010

CDC: SCID is Contraindication for Rotavirus Vaccine

By Todd Neale, Staff Writer, MedPage Today
Published: June 10, 2010

ATLANTA — Rotavirus vaccine should not be given to infants with severe combined immunodeficiency (SCID), according to new CDC guidance.

The makers of the two live rotavirus vaccines — GlaxoSmithKline Biologicals (Rotarix) and Merck (RotaTeq) — had revised their labels in line with the change in December and February, respectively, with FDA approval.

The CDC announced the addition of severe combined immunodeficiency to the list of contraindications for the vaccines in the June 11 issue of Morbidity and Mortality Weekly Report, following consultations with members of the former Rotavirus Vaccine Work Group of the Advisory Committee on Immunization Practices (ACIP) and a review of the data.

Furthermore, “consultation with an immunologist or infectious disease specialist is advised for infants with known or suspected altered immunocompetence before rotavirus vaccine is administered,” the agency said.

Merck and GlaxoSmithKline Biologicals made the labeling changes in response to eight reports of vaccine-acquired rotavirus infection in infants with severe combined immunodeficiency since the 2006 approval of RotaTeq. Seven were related to the pentavalent RotaTeq and the last was related to the monovalent Rotarix, which was approved in 2008.

Five of the cases — four in the U.S. and one in Australia — were reported in the literature and another three — two in the U.S. and one from outside the U.S. — were reported to the Vaccine Adverse Event Reporting System.

All of the infants, who were diagnosed with severe combined immunodeficiency at between 3 and 9 months of age and had received at least one dose of the vaccine before diagnosis, had diarrhea from the rotavirus infection.

In all eight cases, vaccine-acquired rotavirus infection was confirmed by reverse-transcription-polymerase chain reaction and nucleotide sequencing.

Prolonged shedding of the virus was documented in at least six cases with a duration of up to 11 months.

For infants in whom it is not contraindicated, rotavirus vaccination is recommended by ACIP in three doses at ages 2, 4, and 6 months for RotaTeq and in two doses at ages 2 and 4 months for Rotarix.

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125,000/1 against: this boy’s chances of finding a bone marrow donor…

June 8, 2010

125,000/1 against: this boy’s chances of finding a bone marrow donor…

..but were he white it would be a different story. Jerome Taylor reports on the racial lottery for patients in need of transplants

Tuesday, 8 June 2010

Ten-year-old amun Ali desperately needs a bone marrow transplant. If he were white, the likelihood of his finding a life-saving match would be one in three. But he is Asian so his chances are closer to one in 125,000.

The chronic shortage of ethnic minorities on Britain’s various donor registries – be they blood, bone marrow or hard organs – means that the chances of survival for thousands of patients like Amun are drastically reduced.

Patients from South Asian or black backgrounds are three times more likely to need a kidney transplant as white patients. But once they get on to the list they usually have to wait twice as long, which in turn increases the chances of the kidney being rejected because bodies that have had to spend long periods on dialysis often have a harder time accepting new organs.
The sad truth is that for children such as Amun, the road to recovery is fraught with added difficulties simply because of their race.

Things become even more complicated for people of mixed-race backgrounds, where the blending of Britain’s gene pool – considered by geneticists as something that will improve the overall health of our society – makes the search for a suitable transplant fiendishly complex.

Other than the liver, which is remarkably resilient, most donated organs need to come from donors that are both the same blood type and tissue type, otherwise the body’s immune system will kick in and reject the organ. We inherit blocks of tissue type from both our parents, which means mixed-race children often have much more complex or rarer tissue types than the national average.

“Mixed-race patients tend to have the hardest time looking for unrelated donors,” Professor Steven Marsh, the deputy director of research at the Anthony Nolan Trust, says. “If someone inherits a very common Chinese half of their tissue type from one parent and a very common British tissue type from another, then the only people who will really be matches for them are other mixed-race people with the same tissue types.”

This disparity has profound implications for the way we treat our children in the future and how we go about ensuring our donor databases reflect the ever-growing ethnic variety of the British public. A recent paper from the Institute for Social and Economic Research showed that nearly one in 10 British children is now born to mixed-race parents. Taken as a whole category, “mixed race” is now the fastest-growing ethnicity in the UK and yet it is the least represented on all our donor registers.

The Independent recently highlighted the case of Devan Tatlow, a mixed-race four-year-old boy in Washington, DC who is undergoing treatment for leukaemia and desperately needs a bone marrow transplant. His body contains a multitude of genes from his parents, who are of Irish and Indian-Polish descent. When doctors searched the global bone marrow database of 14 million donors they couldn’t find a single match. It took a mass campaign of emailing and pleading by friends, activists and celebrities alike before a potential match was found using cord blood, the stem cell-rich blood that remains in the umbilical cord at birth and is all too often thrown away. Devan’s journey towards full recovery will still be fraught with difficulties, but he has at least found a match.

Yet even when both sets of parents are from the same ethnicity, finding matches can be heartbreakingly difficult for black and ethnic minority (BME) families.

Amun loves wrestling and playing basketball. But for the past six weeks, his home has been a sterile ward at Birmingham’s Heartlands Hospital.

Amun was born with a severe immunodeficiency syndrome that leaves him painfully vulnerable to infections, and in the past few months his condition has deteriorated.

His only chance of long-term survival is a full bone marrow transplant which doctors hope will stimulate his body into creating enough white blood cells to fight off infections.

When his family were told that none of his relatives was a suitable match, they instantly feared the worst.

“We had already lost Amun’s younger brother Ali to the same disease,” said his father, Ashgar Khan, who has since given up his job to care full time for his son. “By the time we discovered his sister was a match it was too late. This time, none of us are matches for Amun.”

The Ali family is aware that the only way they will find a saviour for Amun is to galvanise more South Asians into signing up to the various registries in the hope that somewhere out there is a match. Helped by Desi Donors, one of the only charities working with South Asian donors, they have held a series of “clinics” in and around Birmingham encouraging community members to become donors.

“We haven’t found a match for Amun yet but both times we got about 70 people to sign up,” Mr Khan said. “That might not sound like a lot but in the Asian community it really is.”

Those working within Asian and some black cultures say organ-donating is still viewed with deep suspicion. Feelings tend to be more entrenched among older generations, where culture, customs and some religious communities remain vehemently opposed to the idea of meddling with the body before and, particularly, after death.

“Most of the time, I think it’s just accidental ignorance,” says Reena Combo, who co-founded Desi Donors after meeting Dean Sheikh, a seven-year-old who needed a bone marrow transplant but sadly passed away last year without finding a match. “If you don’t know about something you tend to turn a blind eye to it.”

Leila Molaei, who was involved in organising publicity for an NHS campaign earlier this year encouraging ethnic minorities to join donor registers, says religion is overly criticised for being the main stumbling block.

“It’s more to do with culture rather than religion,” she says. “People of Arab or Iranian descent, for instance, are more comfortable with the idea of becoming a donor than, say, Pakistanis. We tended to find that Hindus are the most relaxed about donorship, followed by Sikhs and then Muslims.”

Professor James Neuberger, the associate medical director for Organ Donation and Transplantation at NHS Blood and Transplant unit, says changing mindsets will not happen overnight. “It’s something we will have to continue working at from different angles over the coming years. But ultimately changing the culture will take a few decades before we start to see any major impact,” he says.

Why does race matter?

What makes a transplantation successful largely depends on whether the recipient’s body accepts the new organ. Those chances are massively increased if the donor has the closest tissue type as possible to the recipient. Race plays a crucial role in deciding our tissue type.

“The genes that are responsible for your tissue type are not there just to confound transplant surgeons,” explains Professor Steven Marsh. “They are there because they have a role in immunity. These genes are constantly changing and mutating. As man has moved around the world, these genes have changed to help us deal with the various pathogens we encounter. The bottom line is someone in China will have a very different tissue type from someone in northern Europe.”

If the tissue type of the donor is different from the recipient, the immune system of the transplant patient will attack the organ. Blood type also plays a crucial role. In Britain the most common blood types are O and A. In South Asia blood types B and A are far more common. Transplant patients with B-type blood in the UK statistically have a smaller chance of finding a suitable organ because their blood type is so much rarer within the wider population.

Religion: Faiths encourage the selfless act of organ donation

Faith leaders from minority religions have gone on the offensive in recent years encouraging devotees to register as organ donors.

Hindu and Sikh religious authorities have few problems with the process. Both view the body as a temporary vessel for the soul and emphasise the importance of selfless giving.

Islam has no qualms with live donorship, like when a parent donates a kidney to their child. But post-mortem organ donation is a little more complicated. Islam places immense importance on the treatment of a body with strict requirements designating how the dead should be washed and prepared for burial without interference. Cutting open bodies, even for autopsies, is sometimes frowned upon.

The majority of sharia schools, however, say organ donation is permissible because of the Islamic concept of al-darurat tubih al-mahzurat, the idea that the necessity of something sometimes outweighs its prohibition. The Koran says that saving one life is akin to saving the whole of mankind and the majority of jurists, including the Muslim Law (Shariah) Council UK, say organ donation is a selfless act that saves lives and should be encouraged. Other shariah schools, however, remain opposed, leading to much confusion.

Christianity emphasises selflessness and sacrifice for the greater good. Although there are no teachings against organ donorship, some church leaders in the developing world preach against it.

Transplants in numbers

1 in 3 The likelihood a white person can find a bone marrow match

1 in 125,000 The likelihood an Asian or Black person can find a bone marrow match

1 in 200,000+ The likelihood a mixed race person can find a bone marrow match

16.9m people on the NHS Organ Donor Register, but only 1.2 per cent of these are from the Asian community and 0.4 per cent of these from Black communities

7,800 patients are actively waiting for a transplant, of whom 1,521 are South Asians and 779 are Black

Between 1 April 2008 and 31 March 2009:

3,513 organ transplants were carried out, thanks to the generosity of 1,853 donors

977 lives were saved in the UK through a heart, lung, liver or combined heart/lungs, liver/kidney, liver/pancreas, heart/kidney or liver/kidney/pancreas transplant
Private Medical Cover from £30 per month with Independent Compare

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Secretary of Health and Human Services Announces Addition of SCID to National Newborn Screening Standards

May 25, 2010

Secretary of Health and Human Services Announces Addition of SCID to National Newborn Screening Standards

TOWSON, Md., May 25 /PRNewswire/ — On May 21, 2010, Kathleen Sebelius, Secretary of Health and Human Services (HHS) announced the addition of Severe Combined Immunodeficiency (SCID) — commonly known as bubble boy disease — to the core panel of 29 genetic disorders — as part of her recommendation to adopt the national Recommended Uniform Screening Panel.  The Secretary made her announcement in a letter to Dr. Rodney Howell, Chair of the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC). SCID is the first nominated condition to be added to the core panel of disorders.

SCID is a primary immunodeficiency disease.  Affected infants lack T lymphocytes, the white blood cells that help resist infections due to a wide array of viruses, bacteria and fungi.  Babies with SCID appear healthy at birth, but without early treatment, most often by bone marrow transplant from a healthy donor, these infants cannot survive.

The Immune Deficiency Foundation (IDF), the national patient organization for persons with primary immunodeficiency diseases, applauds the action by Secretary Sebelius for including SCID in the new national standards.  “The addition of SCID to the national newborn screening standards is a momentous step forward for the primary immunodeficiency community,” said Marcia Boyle, President & Founder of IDF.  “The IDF has strongly supported and worked tirelessly toward this goal for years.  It is imperative that we sustain this momentum by establishing newborn screening programs in all 50 states.”

“Although this recommendation has been in development for two years,” said Dr. Amy Brower, parent, researcher and former SACHDNC committee member, “it may take several more years to implement screening in all 50 states and US territories.  We must work to quickly implement the widespread adoption of testing and treatment in all of the states.”

“As the parent of a child who was diagnosed with SCID only after he became critically ill,” said Barb Ballard, a member of the IDF Board of Trustees, “I am immensely pleased with the action taken by Secretary Sebelius.”

“Our goal is to have Newborn Screening for SCID passed in all 50 states,” said Heather Smith, co-founder of SCID Angels for Life, who lost her six-month-old son, Brandon, to this devastating disease.

For more information, please contact IDF at 800-296-4433, or  Or visit the IDF website at

SOURCE Immune Deficiency Foundation

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B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review.

April 1, 2010

J Allergy Clin Immunol. 2010 Apr;125(4):790-7.

B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review.
Buckley RH.

Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC, USA.

Although bone marrow transplantation has resulted in life-saving T-cell reconstitution in infants with severe combined immunodeficiency (SCID), correction of B-cell function has been more problematic. This review examines B-cell reconstitution results presented in 19 reports from the United States and Europe on posttransplantation immune reconstitution in patients with SCID over the past 2 decades. The analysis considered whether pretransplantation conditioning regimens were used, the overall survival rate, the percentage with donor B-cell chimerism, the percentage with B-cell function, and the percentage of survivors requiring immunoglobulin replacement. The survival rates were higher at those centers that did not use pretransplantation conditioning or posttransplantation graft-versus-host disease prophylaxis. The percentage of survivors with B-cell chimerism, function, or both was higher and the percentage requiring immunoglobulin replacement was lower at those centers that used pretransplantation conditioning. However, there were substantial numbers of patients requiring immunoglobulin replacement at all centers. Thus pretransplantation conditioning does not guarantee that B-cell function will develop. Because most infants with SCID either present with serious infections or are given diagnoses as newborns, one must decide whether there is justification for using agents that compromise innate immunity and have intrinsic toxicities to gain B-cell immune reconstitution. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

PMID: 20371393 [PubMed – indexed for MEDLINE]PMCID: PMC2857969 [Available on 2011/4/1]

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