No More Transfusions,Your Child Can Live Without Beta Thalassemia Major

Following is some interesting information we have came across recently. It's solely your decision whether to get in touch with them or not.

Your child can live without beta thalassemia major with no more transfusions,thanks to Bone Marrow Transplant(BMT),  a 30 years reliable technique applied to more than 3,000 patients worldwide. 89% of low risk children are successfully cured.

Ask the free advice to Dr. Pietro Sodani,our co-founder and scientific coordinator, hematologist, BMT expert and inventor of BMT from haploidentical mother to child with thalassemia using protocol 30,who has done in the last 15 years more than 400 BMT in thalassemia with Prof. Lucarelli,the inventor of BMT from matching sibling and the worldwide authority.
 
With Bone Marrow Transplant (BMT) your child can become beta thalassemia major free (no more transfusions). Each child is different and has his own health conditions.
Dr. Pietro Sodani (co-founder and scientific coordinator. Hematologist, BMT expert and inventor of BMT from haploidentical mother to child with thalassemia using protocol 30,who has done in the last 15 years more than 400 BMT in thalassemia with Prof. Lucarelli,the inventor of BMT from matching sibling and the worldwide authority) gives you via email his free professional advice to tell how your child can have a BMT to be thalassemia free,and what the results might be.

 Go to www.curethalassemia.org  for more details

Q&A with Dr. Ellis Neufeld

We  periodically receives questions from patients on a wide range of topics related to thalassemia and its treatment.  We have shared a few of these questions with Dr. Ellis J. Neufeld, the Chair of CAF’s Medical Advisory Board and Associate Chief, Division of Hematology/Oncology at Boston Children’s Hospital. Dr. Neufeld has kindly answered these questions below.

Dr. Ellis J. Neufeld

1.  What is darker colored urine an indication of in thalassemia patients?
People have been fascinated by urine color for thousands of years.  There’s no single answer to this question, and as for many medical questions, it depends why one is asking. Here are some important things to know.
Generally for persons with thalassemia or without, concentrated urine is darker than diluted urine, and if something is coloring the urine more than normal, this effect will be magnified. Ordinarily the most concentrated urine is first morning void, after not drinking all night.
Many thalassemia patients are used to seeing different color urine from medications like iron chelators.  Deferiprone (Ferriprox) turns the urine orange.  Patients on deferoxamine (Desferal or generic) will have reddish urine when the drug (which is colorless by itself) combines with iron.
Darker yellow to light brown urine in thalassemia is from the bilirubin from broken down red blood cells.  This might be especially pronounced in thalassemia intermedia (non-transfusion-dependent thalassemia) or in transfused patients shortly before a next transfusion is due.
Urine that is truly the color of cola or very dark tea is not normal, and could signal increased breakdown of red blood cells (much more bilirubin than normal). Particularly in the few days after a transfusion, or if a person is feeling more tired than usual, this kind of dark urine should prompt a call to your healthcare provider right away.  A check of the urine and blood tests can be reassuring or point to a problem if one has arisen.
Red urine not related to foods (beets) or deferoxamine or laxatives  (ExLax, phenolphthalein) may reflect either bleeding  or hemolysis (breakdown of blood cells) and should always be investigated.
2.  If we know that orange juice can help in the absorption of iron, should we NOT be taking Exjade with orange juice?
Vitamin C intake and levels in thalassemia should be sufficient, but not excessive.  One glass of OJ a day, or ~100 mg of extra vitamin C a day, is just about right.  It’s fine not to take Exjade with orange juice too, but then there needs to be some other way of assuring vitamin C sufficiency, because chelators work better with adequate vitamin C present.

3.  Drinking tea is supposed to inhibit iron absorption; does that include caffeine-free teas?
Only tea with tannins (the brown bitter stuff in black tea) impairs iron absorption and one has to drink a heck of a lot of tea to have this effect.  Herbal teas, say, may have no tannins. But decaffeinated black tea has a normal amount, only the caffeine is removed.

4.  Have there been any studies that have shown that taking a B-complex vitamin daily can slow the breakdown of red blood cells?
Not to my knowledge.  I have not investigated in detail, but we get B vitamins from our food pretty well.  B vitamins like thiamine and B12 and folate are absolutely required to make blood, but that’s a different story.

5.  Can you address whether Exjade should be split into 2 equal doses taken every 12 hours (rather than one every 24), and how combining it with food can affect its effectiveness?
a. “Should be” is a discussion best had with your hematologist.   Exjade CAN BE split into two doses a day, and they don’t necessarily have to be equal, so that if you use three tablets daily, you might split 2 and 1.  There are several theoretical reasons why splitting twice daily might be advantageous.  First, there is less load of the drug all at once. This helps prevent stomach aches and loose stools in some patients on high doses. Second, although on the average, the drug can last up to around 24 hours in the blood, some patients have shorter drug “half-lives” in the blood, and splitting the dose means coverage through more of the day. Third, in a few published abstracts, and in the experience of many treaters, Exjade may be more effective split twice a day (or it may allow higher doses, which are more effective, if it allows less GI side effects).  So at our center we offer or urge twice a day in case of abdominal symptoms or not good-enough effect at higher dose.  Also, see the answer about combining with food (in part b of this answer). If it doesn’t need to be on an empty stomach, twice a day Exjade is much less of a burden.
b. In a study carried out at many expert centers around the world, sponsored by Novartis (the manufacturer), it was proven that Exjade is at least as effective taken with food as not.  As you know, the drug doesn’t dissolve well in water, that’s why it makes a chalky slurry. It dissolves better in fatty foods, and this may be why this is a good option. So we counsel patients  that they can crush the tablets and mix in most anything (but don’t cook or microwave it), and that’s fine. The DRUG LABEL still says to take on an empty stomach in liquid, but we believe this may be because the drug will soon go off-patent, and Novartis hasn’t gotten around to making this change on the label, perhaps for commercial reasons.

6.  Is clumping of platelets a side effect of thalassemia trait?
No.  Rare people have clumping of platelets that isn’t a disease but a lab artifact called “pseudothrombocytopenia” (pseudo as in not real), and your hematologist can sort that out by counting your platelets in a different anticoagulant (that is, a blue top tube instead of purple top).

7.  Are there tests other than creatinine levels to detect kidney damage early?
Yes. This is an important point.  The Exjade package label has specific information on testing for protein in the urine for example.  Exjade raises most everyone’s creatinine without causing significant kidney damage, and then does cause renal disease in a small subset of that group, not related to the creatinine alone.

8.  Is blood warming beneficial to decrease antibody reactions and/or antibody buildup?
In patients with temperature-specific antibodies to red cells, definitely.  In patients without such antibodies, no.  Your center’s blood bank would know this for you. There is no call for general blood warming for example.

Go Get ‘Em, Tiger! One Patient’s Approach to Thalassemia

Marsha DeSalvatore understands the saying about making lemonade when life hands you lemons; this talented and vivacious woman has learned to use the fact that she has thalassemia as a way to express herself through comedy and improvisation. In doing so, she helps herself and educates others about what it means to daily live with a chronic condition. Marsha recently shared her experiences.

You have been using humor as a way to explore thalassemia. Can you talk a little about what you have done, how it helps, etc.?
Marsha: Ever since I was a child, I was aware of how laughing made me feel while I was going through unpleasant situations at the hospital. I have been blessed with a very funny father who is always telling stories, doing impressions and being entertaining. When he came to the hospital to visit me, he would try to make me laugh and that’s when I realized that in those moments I was transported out of what was happening: sad clinic, smells of hospital stuff, needle in my arm, sounds of the transfusion monitor and blood going through my body. Laughing made me feel good even in this unpleasant situation.

Marsha leading a workshop on improvisation and thalassemia at 2014 Patient-Family Conference

Now I am blessed again to be in Rome and have a doctor who prides himself on being the Italian Patch Adams. He is always teasing the patients, telling jokes and making fun of the nurses which makes the clinic into an almost comedy club. Again those moments are when I am transported to happy place whilst being in a painful place.
While living in Rome, I discovered my actress side. I started taking acting classes which eventually led me to working as a comedian today. In the classes, I had to take improv (improvisation) classes. Improv is a form of acting which allows the person to think on their feet in the moment with no script. The goal (in brief words) is working on being in the moment, letting go of your inhibitions, getting out of a person’s comfort zone and having fun. The exercises range from simple warm up exercise to name games to later on evolving scenes with partners that become 2-3 minute mini-plays. As I started getting into this art form which helps me on stage as a comedian, I began to feel the same thing as I did when I was in the hospital: that I was transporting myself to a happy place in a rather uncomfortable situation and applying some of the improv rules to help with everyday life with a chronic illness.

How would you express your philosophy of dealing with the challenges that thalassemia can present?
Don’t fight it, embrace it and find an outlet that gives you happiness whether it’s through exercise or art.
For sure, you will have days when you need to cry, scream, or be alone, but embrace those moments. This is not something that goes away, so try to find ways to live with it.  Remember you are in charge of your illness; it makes up a small percentage of who you are. Find out what you like and who you are.  Use those tools to have an outlet.
For me, it’s laughing with friends, travelling, taking a walk in nature, doing yoga and acting which helps me feel better.  When I get down with my constant hospital life, I do something for myself.

Do you have any advice that you would pass on to others with thalassemia?
As my wise father has always told me, in his thick Italian accent, “Marrrsshha, you got two ways to deal with this thalassemia: you can be angry and hit your head against the wall, but then it is going to bleed – and you need the blood.  Or you can smile and go get ‘em, Tiger!”
Is there anything else you’d like to say?
I hope to be able to use my comedy and do improv with patients of any illness because the thought of giving them a moment of laughter in a moment of pain makes my life as a comedian so much more gratifying. Better than any audience I could ever have.

Thalassemia Patient Authors “Transfusion: A Patient Survival Guide”

Josephine Bila, an individual with thalassemia, has written a book, “Transfusion: A Patient Survival Guide.” 


Tell us a little about “Transfusion: A Patient Survival Guide.”  What motivated you to write it, what is it about, etc.?
Jo:  I was born with beta thalassemia major, so my life depends on receiving transfusions. I’ve been getting them every few weeks for over 35 years. When I was in my twenties, I used to receive blood in an adult outpatient hematology oncology unit. The floor plan was open, so patients would sit in large reclining chairs that were parallel and facing each other. There was a man with cancer who would sit across from me and stare at me for almost the entire duration of my treatment. I would pretend to sleep, but every now and then I would open my eyes and see him gazing at me. In my ever so slight glances, I noticed how this man expressed an intense displeasure and discomfort with his transfusion treatment. He would groan and moan and hold his arm as stiff as a plank of wood. That’s when I realized that he was looking at me curiously not only because I was young, but also because I had emotionally and physically conquered my fear and discomfort with transfusions. I would laugh with the nurses and feel completely tolerant of my pain. That’s when I began to think about how much coping strategy I had taught myself over my lifetime. It’s when I recognized that the tools and practices I had accumulated over the years could be shared and potentially save people from suffering the way I once did.

What are the “take home messages” that you hope readers will pick up from the book?
The primary message of “Transfusion: A Patient Survival Guide”  is that you have a lot more control over your experience in the hospital than you might think. The book shares personal stories from my life that describe how I managed to transform my negative thought patterns and extremely painful physical experiences (I used to get transfusion reactions) into positive thoughts and virtually pain-free physical outcomes.

What was the process of creating the book like?
The process was pretty strange, to be honest. I wrote the entire book two years ago by waking up at two o’clock in the morning and writing for an hour or so over the course of two months. I had a compulsion to put my thoughts onto paper – as if the words had been formulating since the day I noticed that old man suffering. Everything came together with very little effort on my part. The book’s interior design, however, was much more difficult to create. A good friend of mine laid out each page individually and beautifully, in full color, so I feel like he deserves a lot of the credit too.

Do you see this book as an extension of your advocacy efforts on behalf of the thalassemia community and/or the overall patient community?
Yes. I absolutely know for a fact that this book will help any patient or parent of a patient, simply because we need to know how people like ourselves cope and achieve peace in life. I didn’t know any thalassemia patients as I was growing up. Now I go to a hospital where I’m one of many, so I feel so at ease knowing that I’m not alone in my experiences. I want other people to feel this sense of peace. I want parents to know how to console their child when he or she is in need of transfusions. Most of all, I want any person who reads the book to come away feeling stronger, more powerful, and much happier.

What else would you like to share about the book?
You can only buy the book on Amazon (at the moment): amzn.to/1mm2sJW .
I also created a guided meditation to accompany the book, which can be acquired on this page: transfusionsurvivalguide.com.

Is there anything else you’d like to share or to say to those with thalassemia?
Yes, I would love to say that living with thalassemia is not easy. I wasn’t always a beacon of light for people. I spent most of my life angry, sad, and ashamed of having a blood disorder. Then I realized that I was the one designing my life. I decided early on that I could either choose to live a life of misery or I could choose to live a life of happiness. I took the high road. We all have this choice and sometimes it takes an enormous amount of inner strength to push through our own negative momentum, but I know it’s possible. I’m living proof of this fact. I’d love to see you try one small step towards happiness each day. We are so much stronger than we sometimes allow ourselves to be in all areas of life. Let’s show the world what we’re made of!

Findings could lead to treatments for blood disorders associated with iron deficiencies and overloads

A UCLA research team has discovered a new hormone called erythroferrone, which regulates the iron supply needed for red blood-cell production.

Iron is an essential functional component of hemoglobin, the molecule that transports oxygen throughout the body. Using a mouse model, researchers found that erythroferrone is made by red blood-cell progenitors in the bone marrow in order to match iron supply with the demands of red blood-cell production. Erythroferrone is greatly increased when red blood-cell production is stimulated, such as after bleeding or in response to anemia.
The erythroferrone hormone acts by regulating the main iron hormone, hepcidin, which controls the absorption of iron from food and the distribution of iron in the body. Increased erythroferrone suppresses hepcidin and allows more iron to be made available for red blood-cell production.
"If there is too little iron, it causes anemia. If there is too much iron, the iron overload accumulates in the liver and organs, where it is toxic and causes damage," said senior author Dr. Tomas Ganz, a professor of medicine and pathology at the David Geffen School of Medicine at UCLA. "Modulating the activity of erythroferrone could be a viable strategy for the treatment of iron disorders of both overabundance and scarcity."
The early findings were reported online June 1 in the journal Nature Genetics.
"Our previous work anticipated that a regulator of hepcidin could be secreted by the bone marrow," said the study's first author, Leon Kautz, a postdoctoral fellow at UCLA. "In this research, we searched for new substances that were made in bone marrow that could fill that role."
Researchers first focused on what happens in the bone marrow after hemorrhage. From there, they focused on a specific protein that was secreted into the blood. This protein attracted their attention because it belonged to a family of proteins involved in cell-to-cell communication.


Using recombinant DNA technology, they showed that the hormone suppressed the production of hepcidin and demonstrated the effect it had on iron metabolism.
The team foresees that the discovery could help people with a common congenital blood disorder called Cooley's anemia, also known as thalassemia, which causes excessive destruction of red blood cells and of their progenitors in the bone marrow. Many of these patients require regular blood transfusions throughout their lives. Most iron overload is attributed to the iron content of transfused blood. However, even patients who are rarely, or never, transfused can also develop iron overload.
"Overproduction of erythroferrone may be a major cause of iron overload in untransfused patients and may contribute to iron overload in transfused patients," said study author Elizabeta Nemeth, a professor of medicine at the David Geffen School of Medicine at UCLA and co-director of the UCLA Center for Iron Disorders. "The identification of erythroferrone can potentially allow researchers and drug developers to target the hormone for specific treatment to prevent iron overload in Cooley's anemia."
The discovery could also lead to treatments for other common anemia-related conditions associated with chronic kidney disease, rheumatologic disorders and other inflammatory diseases. In these conditions, iron is "locked up" by the effect of the hormone hepcidin, whose levels are increased by inflammation. Erythroferrone, or drugs acting like it, could suppress hepcidin and make more iron available for red blood-cell production.
The next stage of research is to understand the role of the new hormone in various blood diseases and study the molecular mechanisms through which erythroferrone regulates hepcidin.

Source:

University of California - Los Angeles Health Sciences

Atpif1 gene regulates heme synthesis in red blood cell formation

Scientists at the University of Georgia, Harvard Medical School and the University of Utah have discovered a new gene that regulates heme synthesis in red blood cell formation. Heme is the deep-red, iron-containing component of hemoglobin, the protein in red blood cells responsible for transporting oxygen in the blood.
The study was published online Nov. 7 and will be in the Nov. 22 print edition of the journal Nature. The findings promise to advance the biomedical community's understanding and treatment of human anemias and mitochondrial diseases, both known and unknown.
The gene-known as mitochondrial ATPase inhibitory factor-1 gene or Atpif1-was uncovered from a chemical mutagenesis screen of zebrafish, an organism which shares many of the same genes that regulate blood development in humans.
"With zebrafish, we are able to accelerate natural disease processes and screen for many more mutations in blood than we could ever see in random circumstance of human patients," said study senior co-author Dr. Barry Paw, a hematologist and associate professor of medicine at Harvard Medical School.
"In our case, we were looking for mutants that were bloodless, presumably because whatever gene that was inactivated by the random mutation must be critical for blood development, if one of these embryos were bloodless."
That is what Paw and his team found when they stumbled upon the particular "bloodless" mutant zebrafish called pinotage. The loss of the Atpif1 gene was the cause of the fish's severe anemia.
The next step for the team was to determine if the anemia was a defect of iron metabolism or heme homeostasis. Collaborating with molecular biologist Jerry Kaplan at the University of Utah, the researchers discovered a possible link between Atpif1 and ferrochelatase, the terminal enzyme in heme synthesis.
UGA microbiologist Harry Dailey, a leading authority in the structure and function of ferrochelatase, was brought on board. Collaborative work between the Paw and Dailey laboratories uncovered a broader mechanistic role for Atpif1 in regulating the enzymatic activity of ferrochelatase.

"We believe that the two iron-two sulfur (2Fe- 2S) cluster of ferrochelatase allows it to sense certain metabolic fluxes in the cell and respond to those fluxes in an appropriate way," said Dailey, who is a professor of microbiology and director of the UGA Biomedical and Health Sciences Institute. "When Atpf1 is deficient, there is a change in the mitochondrial pH/redox potential. This change is sensed by the cluster, and ferrochelatase activity is turned down, which results in diminished heme synthesis."
The researchers also were able to produce data on the human version of Atpif1, noting its functional importance for normal red blood cell differentiation as well as how a deficiency may contribute to human diseases-such as congenital anemias and disorders related to dysfunctional mitochondria, the organelles that power the cell.
Overall, Dailey believes the study's results will impact the field of red blood cell development significantly with the establishment of the ferrochelatase [2Fe-2S] cluster as a new regulatory component in heme synthesis. New areas of investigation will open, he said, and the molecular basis of currently undefined red blood cell-based syndromes and diseases may be revealed.
Source: University of Georgia

Atpif1 gene regulates hemoglobin synthesis during red blood cell formation

Researchers at Brigham and Women's Hospital (BWH) have discovered a new gene that regulates hemoglobin synthesis during red blood cell formation. The findings advance the biomedical community's understanding and treatment of human anemias and mitochondrial disorders.
The study will be published online on November 7, 2012 in Nature.
The researchers used an unbiased zebrafish genetic screen to clone mitochondrial ATPase inhibitory factor-1 gene, or Atpif1. The gene allows animals-zebrafish, mice and humans for instance-to efficiently make hemoglobin. Hemoglobin is the protein in red blood cells responsible for transporting oxygen in the blood.
The researchers found that loss of Atpif1 causes severe anemia. Moreover, the researchers uncovered a broader mechanistic role for Atpif1-regulating the enzymatic activity of ferrochelatase, or Fech. Fech is the terminal enzyme in heme (a component of hemoglobin) synthesis.
"Our study has established a unique functional link between Atpif1-regulated mitochondrial pH, redox potential, and [2Fe-2S] cluster binding to Fech in modulating its heme synthesis," said Dhvanit Shah, PhD, BWH Division of Hematology, Department of Medicine, first study author.
The researchers were also able to produce data on the human version of Atpif1, noting its functional importance for normal red blood cell differentiation, and noting that a deficiency may contribute to human diseases, such as congenital sideroblastic anemias and other diseases related to dysfunctional mitochondria (the energy powerhouses of cells).

"Discovering the novel mechanism of Atpif1 as a regulator of heme synthesis advances the understanding of mitochondrial heme homeostasis and red blood cell development," said Barry Paw, MD, PhD, BWH Division of Hematology, Department of Medicine, senior study author.
Shah and Paw continue to identify new genes responsible for hematopoietic stem cell development and red cell differentiation. Their identification of new genes will elucidate the new mechanisms regulating hematopoiesis-the formation of blood cell components. Their work not only provides greater insight into human congenital anemias, but also new opportunities for improved therapies.
Anemia, a condition in which your blood has a lower than normal number of red blood cells or hemoglobin levels, can affect people of all ages. Women of childbearing age and older adults are at higher risk. Babies and children are also at risk for anemia due to nutritional iron deficiency or lead poisoning.
Source: Brigham and Women's Hospital

"Meeting, Overcoming and Understanding Life’s Challenges" - Patient Profile of Rucha Shah

For 25-year-old Rucha Shah, the hardest part of living with thalassemia is the impact it has on her family.  

“The most difficult thing for my family is making sure that I am healthy and will remain healthy in the near future,” Rucha explained. “Most parents of young adults do not have to worry about that.”

It’s hard to overstate the strain on families from a lifelong blood disorder like thalassemia. Rucha and her family have worked hard to maintain good health ever since she was diagnosed at just seven months old.

The Shah family was living in Mumbai, India at the time. Under the care of a local hematologist, Rucha underwent regular blood transfusions and took a chelation medication called L1 (also known as deferiprone)  to keep her iron levels under control. Iron buildup in vital organs, particularly the heart, is one of the main causes of early fatality for patients like Rucha.

Rucha’s family kept up-to-date about the latest research, medications and other information through newsletters from the Cooley ’s Anemia Foundation (CAF), which they learned about through one of their relatives. Especially early on, these newsletters were helpful in guiding family decisions about their daughter’s well being.

"Thalassemia, although a huge part of my life, does not dictate it.”

When she was 16, her hematologist placed her on a more aggressive regimen of iron-chelating medications, adding Desferal injections to Rucha’s routine. That meant enduring almost-daily needle jabs and between eight and 12 hours of being attached to a subcutaneous injection pump. And that’s one of the hardest things for parents of children with thalassemia: the treatments require long stretches of time and are often painful.

Rucha’s treatment regimen became even more complicated at age 18, when her family immigrated from Mumbai to the Philadelphia, Pennsylvania area in 2005. The L1 medication that she’d taken all her life hadn’t yet been approved in the United States (it received FDA approval in 2011 and is now available), and so she had to depend solely on Desferal injections. In 2006, she began using a newly approved oral chelation medication called Exjade, and has been taking it ever since.

In addition to the difficulty of switching medications, Rucha had to contend with the challenges of life in a new country.

“The hardest thing was settling down, making new friends and understanding new culture,” Rucha said. “And there’s the added difficulty of explaining to friends that I have thalassemia.”

“And there are also physical difficulties,” she continued. “At the end of the day, I just want to go home and crash in my bed, especially few days before my next transfusion. I see my friends go out and have a good time after work or school is over. That is hard for me.”

Difficulties aside, Rucha was determined to meet all of these challenges, and more. With resolve and support from her family, she went to college to study the very things that had both complicated her life and helped keep her healthy.

	“I am as optimistic and capable of achieving my dreams as anybody else.”

   

“I received my Bachelor of Science degree in biochemistry. And right now, I’m considering post-graduate studies in biomedical sciences, clinical or basic research,” she explained. “I have always been fascinated by how our body works and how genes, proteins and biochemical messengers send signals to various parts of our body.”

It’s always difficult for a family – and especially a child – to understand illnesses and why their bodies don’t always work the way other peoples’ bodies do. Rucha Shah, whose life has involved all kinds of medications and treatments, is trying to develop a deeper understanding of those things, in the hope of helping others like herself and her family. She’s still receiving helpful information and social support from CAF to help her along the way.

“I am as optimistic and capable of achieving my dreams as anybody else,” Rucha said. “Thalassemia, although a huge part of my life, does not dictate it.”

Help CAF Keep Helping Patients Like Rucha. Click Here to Make an Online Donation.

Story: Roger Burks ____ Photos: Thatcher Hullerman Cook

Mechanical treatment shows promise in thalassemia

By Laura Cowen
Vibration therapy may be an effective nonpharmacologic intervention to increase bone mass in patients with thalassemia, US researchers report.
The pilot study, conducted among nine adults (age >18 years) and nine adolescents (age 10-18 years), showed that standing on a vibrating platform (30 Hz, 0.3g) for 20 minutes per day for 6 months increased whole-body bone mineral content (BMC) by a significant 2.6% compared with baseline.
Areal bone mineral density (aBMD) and BMC/height, both measured by dual-energy X-ray absorptiometry, increased by a significant 1.3% and 2.6%, respectively, during the intervention period, and remained elevated at 12 months.
Furthermore, the rate of change in hip BMD during the 6-month intervention in adults was significantly greater than the change observed in the year before study entry (2.2 vs -2.7%).
"Though these data are preliminary, they suggest promise of a non-invasive intervention in a group of patients who have a significant risk of osteoporosis morbidity," remark Ellen Fung (Children's Hospital and Research Center, Oakland, California) and co-authors in the American Journal of Hematology.
Fung and team explain that patients with thalassemia have low bone mass, which can lead to fracture and decreased quality of life.
Patients are commonly treated for hypogondism through hormonal supplementation and encouraged to take calcium and vitamin D, but the majority continue to lose bone, as much as 1% to 2% per year, as they age.
Mechanical stimulation through whole-body vibration has been shown to promote bone formation in previous studies, the researchers therefore tested its efficacy in thalassemia.
The increases in aBMD and BMC were accompanied by significant increases in levels of the bone formation marker osteocalcin and decreases in the bone resorption marker serum collagen type 1 cross-linked C-telopeptide.
Of note, although aBMD and BMC increased during the intervention period among adolescents, the increase was no greater than that recorded in the 6 months prior to the intervention. This was possibly because adolescents were captured during a period of rapid growth and pubertal development, limiting the ability to observe change, Fung et al remark.
They conclude: "Future research is needed to confirm these findings in a larger sample for longer duration."

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

Haploidentical bone marrow transplants for sickle cell disease: an interview with Dr. Javier Bolaños Meade

 Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)

Please could you give a brief introduction to bone marrow transplants?

Bone marrow transplant (also called stem cell transplant) is a medical intervention that allows a physician to deliver very high doses of chemotherapy (if needed) but more importantly, deliver a new immune system to the patient to fight a disease (such as cancer).
For instance, if a patient has leukaemia, and I give that patient a transplant from a donor, he will get a new immune system that will fight the leukaemia, and will also get a new marrow to produce blood (the marrow is the part of the body in charge of making new blood).
In the case of patients with sickle cell disease (and related disorders) the important point is to replace the marrow that is producing defective red cells, for a new marrow that produces healthy red cells.

What exactly is a haploidentical bone marrow transplant?

Historically, in order to perform a bone marrow transplant, donor and recipient have to be 100% matched at the HLA genes level (human lymphocyte antigen). Many patients cannot get a transplant because they lack this matched donor.
But we have shown already in patients with cancer that they can receive a bone marrow transplant from a 50% match (or haploidentical). Over 90% of patients will have a sibling, child or parent that may be used as a donor and in the large majority (almost 100% but not quite) these first degree relatives will be at least 50% match. Therefore, if the patient’s sibling is not a perfect match but at last 50% may be still a good donor.

How did your work on haploidentical transplants for sickle cell disease originate?

Originally we start working on haploidentical transplants on patients with cancer (leukaemia, lymphoma, etc) at the end of the XX century – late 1990’s. Once we established that it was a safe procedure we wanted to test it in patients with non-malignant (non-cancer) conditions like sickle cell for which it is very difficult to find fully matched donors, either because their siblings are also affected, or they cannot find unrelated donors through registries like the National Marrow Donor Program. So, in these cases, a haploidentical transplant may be a good option.

How does a haploidentical bone marrow transplant eliminate sickle cell disease?

When we give new bone marrow to a patient, the donor’s immune system will allow the new marrow and immune system to establish its dominance in the recipient. Then, the donor’s marrow will start making new red cells that are healthy as opposed to those made by the sickle cell marrow.
The abnormal red cells in sickle cell cause many health problems. Once the new and healthy red cells are produced, one can expect that no new complications will develop. However, the damage already done by the sickle cell will not be reversed.

Does a haploidentical transplant always eliminate sickle cell disease or do some patients need a fully matched transplant?

We only performed a haploidentical transplant if the patient does not have a fully matched donor. But transplants do not always eliminate sickle cell. Approximately 50% of the haploidentical transplants done for sickle cell have been successful.

What are the benefits of a haploidentical bone marrow transplant?

Haploidentical transplant offers the possibility of finding donors for patients who otherwise would not be able to receive a transplant. Haploidentical donors (close relatives) are usually willing to donate and are usually readily available. It increases the pool of potential donors. In our study, a large majority of patients would not have received transplants without a haploidentical donor since they lacked a fully matched donor.

Are there any dangers of a haploidentical bone marrow transplant?

Yes, bone marrow transplant is a dangerous procedure that can be life threatening. Infections, graft-versus-host disease, organ toxicities are commonly seen after transplant and these can be very dangerous.

Are there any plans to use haploidentical bone marrow transplants for other conditions?

Currently at Johns Hopkins we have clinical trials with haploidentical transplants available for patients with blood cancers such as leukaemia, lymphoma, etc. We also have it available to patients with sickle cell disease and other haemoglobinopathies such as thalassemia. There are plans to expand to other diseases but that will be in the future.

How do you think the future of bone marrow transplants will develop?

The transplant community is actively researching ways to perform transplants with less toxic approaches, decreasing the rates of complications such as graft versus host disease. I think the areas receiving more attention now are:

1. Alternative donors (such as haploidentical or cord cell grafts)
2. Reduction of graft versus host disease

What plans do you have for further research in this field?

We are currently studying if increasing the number of cells infused in the graft will increase the success in patients undergoing transplants for sickle cell disease.

Would you like to make any further comments?

Despite the fact that transplantation is the only curative therapy for patients with sickle cell disease, it is not the only available option. Not all patients are candidates (either because they do not have severe enough disease or because their overall health is poor).

Where can readers find more information?

http://www.cancer.gov/clinicaltrials/search/view?cdrid=675373&version=HealthProfessional&protocolsearchid=10925161
http://www.hopkinsmedicine.org/news/media/releases/half_match_bone_marrow_transplants_wipe_out_sickle_cell_disease_in_selected_patients

About Dr. Javier Bolaños Meade

Dr. Javier Bolaños Meade is the Associate Professor of Oncology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.
His expertise includes:

• Bone Marrow Transplant
• General Internal Medicine
• Graft-versus-Host Disease
• Hematologic Malignancies

His group is researching into finding novel therapies for the treatment of both acute and chronic graft versus host disease (GVHD).

"We're driven to do big things." - Patient Profile of Robert Mannino

Source: http://www.thalassemia.org


Robert Mannino knows more about blood transfusions than most people.  Diagnosed with thalassemia when he was just six months old, he’s spent much of his life in clinics, hooked up to transfusion machines for treatment of the disorder – at least once every three weeks for six hours at a time. 
   

Now 20 years old and a junior at the Georgia Institute of Technology (Georgia Tech), Robert is turning that life experience into motivation for studying his chosen field: biomedical engineering.

“I’ve always been interested in science and math.  And being in a hospital all the time growing up, and getting to know a lot of people with blood-related illnesses, I wanted to use my talents to help others,” he says.

One of the people he most wants to help is his 15-year-old brother, Kevin, who also has thalassemia.  Robert says that theCooley’s Anemia Foundation (CAF) has been there for his family throughout his life, pioneering research and improving treatment centers to make transfusion days more bearable.  And, more recently, CAF helped Robert in another very significant way: providing a scholarship for him to study ways to help his fellow patients.

Robert wants to help his 15-year-old brother who also has thalassemia.

 This semester, Robert is enrolled in 17 hours of classes at Georgia Tech.  Each weekday, he typically spends three hours in the classroom, three hours in the lab and at least three hours on homework.  Part of his work in the laboratory involves hands-on work with the kinds of machines he encounters each time he goes for a blood transfusion.

“I’m working on a project where I choose a medical device, figure out its flaws and strengths, tear it apart and put it back together again,” he explains.  “There are a lot of engineering components, as well as mechanical and biological considerations.”

 As Robert works in the lab, answering questions for this story, his fellow researchers stop to ask him what the interview is about.

“I don’t know if you know this, but I have a medical condition called thalassemia, and these are guys from the Foundation that supports me,” he tells them.  This happens on several occasions and, each time, Robert is brave and patient in his explanation.

He says that research work in the lab is one of his favorite parts of the day; in fact, he enjoys it so much that he wants to go to graduate school to study hematology. Eventually, he’d like to work for a medical device company, building better products to improve the lives of those with blood disorders. It’s something that he knows, and feels, from a lifetime of experience.

	"We're driven to do big things."

 “There’s something different about people confronted with hardships like this,” Robert says.  “We’re driven to do big things.” 

"Thalassemia was emotionally taxing on my family, but we adapted" - Patient profile of Aaron Cheng,

My name is Aaron Cheng, and I’ve just completed my first semester of college at Harvard

University.

I don’t remember when I was diagnosed with beta thalassemia major, which is also known as Cooley’s Anemia, but my parents tell me it was when I was around one year old.  We were visiting Taiwan, and my mother and father noticed specks of blood in my diaper.  Soon afterward, doctors told my parents that I had Cooley’s anemia. 

I’ve been under treatment for as long as I can remember. From when I was an infant to when I became a middle-schooler, I took Desferal infusions four times a week.  The Desferal treatment would last for about eight hours every night, from when I went to sleep to when I woke up. Treatment now is definitely a lot more convenient: instead of having injections every night, I use the oral chelator Exjade every night, so my schedule is a lot more flexible now.  I am so thankful that treatment is becoming a lot more convenient for Cooley’s anemia patients; as a college student, I find taking a pill a lot easier than injecting a drug for eight hours every night. 

I remember that as a child thalassemia was a lot more painful for my family and me than it is now.  The most difficult aspect for me was feeling different from my friends, since I would be noticeably absent from school when I visited the doctor.  I think the hardest part for my parents was trying to deal with the disease and make sure I had a balanced life.  Thalassemia was emotionally taxing on my family in the early part of my life, but we quickly adapted to the new lifestyle, and now it feels like thalassemia is nothing more than an easily managed inconvenience. 

Besides keeping up with my medicine every day, I don’t think thalassemia greatly impacts my life.  I am still able to lead a perfectly normal college life and try new things every day.  Perhaps thalassemia might make me more tired than the average person when it gets close to a transfusion day, but I find college exciting enough that any physical effect that thalassemia has on me is usually barely noticeable. 

My family first found out about the Cooley’s Anemia Foundation when my doctor introduced my father to the association.  From then on, my family has been very involved, and I attend conferences as often as I can.  It has offered a great community through which I can share my experiences and learn from others who have thalassemia as well.  I find the Foundation to be an extremely helpful forum for patients and family; my family and I have met many friends and gotten a lot of help coping with thalassemia through the CAF.  

I decided to attend Harvard primarily because it had always been my dream school; I love the Boston area and thought it would be a great experience to live on the East Coast and learn in such an academically-driven community.  Furthermore, the Boston area is very convenient, and I am able to go to the Boston Children’s Hospital quickly every three weeks for my transfusions. 

It was such a surprise for me when I was accepted to Harvard and I knew right when I found out that I couldn’t turn this opportunity down.  It has been a great experience for me so far; I am involved in the Harvard Crimson (Cambridge’s daily newspaper), and the Harvard Square Homeless Shelter where I volunteer.  I’ve enjoyed all of my classes so far and learned so much.  Right now I am unsure what I will study for a major, but I am strongly considering molecular/cellular biology, neurobiology, or applied math with a focus on biology.  I am keeping my career options open until I find out in the coming years what I enjoy most.  

Adjusting to a new climate away from my family was easier than I imagined, partly because Harvard keeps me so busy and also because the people there are so friendly that it took a very short time for me to make a lot of new friends.  The weather is noticeably colder than sunny Southern California, but I’ve been having a lot of fun experiencing the new climate. 

The adjustment to Boston Children’s Hospital has been exceptionally smooth; every three weeks I go to the nearby clinic to get my blood drawn, then on the Saturday after I take a 20-minute bus ride to Boston for my transfusion. 

The future looks bright, and I’m looking forward to learning so much more and having the opportunity to give back to the community!

 

New gene transfer technique can treat beta-thalassemia, sickle cell anemia

A team of researchers led by scientists at Weill Cornell Medical College has designed what appears to be a powerful gene therapy strategy that can treat both beta-thalassemia disease and sickle cell anemia. They have also developed a test to predict patient response before treatment.
This study's findings, published in PLoS ONE, represents a new approach to treating these related, and serious, red blood cells disorders, say the investigators.
"This gene therapy technique has the potential to cure many patients, especially if we prescreen them to predict their response using just a few of their cells in a test tube," says the study's lead investigator, Dr. Stefano Rivella, Ph.D., an associate professor of genetic medicine at Weill Cornell Medical College. He led a team of 17 researchers in three countries.
Dr. Rivella says this is the first time investigators have been able to correlate the outcome of transferring a healthy beta-globin gene into diseased cells with increased production of normal hemoglobin -- which has long been a barrier to effective treatment of these disease.
So far, only one patient in France has been treated with gene therapy for beta thalassemia, and Dr. Rivella and his colleagues believe the new treatment they developed will be a significant improvement. No known patient has received gene therapy yet to treat sickle cell anemia.
A Fresh Approach to Gene Therapy
Beta-thalassemia is an inherited disease caused by defects in the beta-globin gene. This gene produces an essential part of the hemoglobin protein, which, in the form of red blood cells, carries life-sustaining oxygen throughout the body.
The new gene transfer technique developed by Dr. Rivella and his colleagues ensures that the beta-globin gene that is delivered will be active, and that it will also provide more curative beta-globin protein. "Since the defect in thalassemia is lack of production of beta-globin protein in red blood cells, this is very important," Dr. Rivella says.
The researchers achieved this advance by hooking an "ankyrin insulator" to the beta-globin gene that is carried by a lentivirus vector. During the gene transfer, this vector would be inserted into bone marrow stem cells taken from patients, and then delivered back via a bone marrow transplant. The stem cells would then produce healthy beta-globin protein and hemoglobin.

This ankyrin insulator achieves two goals. First, it protects delivery of the normal beta-globin gene. "In many gene therapy applications, a curative gene is introduced into the cells of patients in an indiscriminate fashion," Dr. Rivella explains. "The gene lands randomly in the genome of the patient, but where it lands is very important because not all regions of the genome are the same." For example, some therapeutic genes may land in an area of the genome that is normally silenced -- meaning the genes in this area are not expressed. "The role of ankyrin insulator is to create an active area in the genome where the new gene can work efficiently no matter where it lands," Dr. Rivella says. He adds that the small insulator used in his vector should eliminate the kind of side effects seen in the French patient treated with beta-thalassemia gene therapy.
The research team also discovered that the insulator increases the efficiency by which the beta-globin gene is transcribed during the process of making the red blood cells. "We found the gene is integrated into cells which have not yet begun to make red blood cells, and when they do, the beta-globin gene is activated," Dr. Rivella says. "We showed that if the insulator is present, activation of the curative gene is more efficient. This provides more curative protein to red blood cells."

The study further provides evidence that the vector had different rates of efficiency depending on the beta-thalassemia mutation it was used in -- thus providing the basis for a predictive test in patients. The investigators tested 19 different beta-thalassemia samples comprising the two types commonly found in patients -- "beta-zero" cells that do not produce any beta-globin (forcing patients to receive blood transfusions throughout life), and "beta-plus" cells that produce suboptimal levels of hemoglobin. On average, they found that one copy of the vector in beta-zero cells produced 55 percent of the adult hemoglobin seen in normal individuals. Beta-plus cells, after treatment, produced hemoglobin comparable to a healthy individual, and were thus cured.
"The variable nature of the beta-thalassemia mutations suggests that some patients would be better candidates for gene therapy than others, and that success of gene therapy depends on the ability of a specific vector to make hemoglobin," Dr. Rivella says. "This is something we can test in advance using a little bit of a patient's blood -- which is quite extraordinary."
The issue in sickle cell anemia is very different, Dr. Rivella says. The hemoglobin protein is made in the right quantities, but it is not normal -- the red cell is shaped like a sickle and is abnormal in function. "One of the problem in gene therapy of sickle cell anemia is to add a new gene without increasing too much the total amount of protein, both normal and sickle. This would cause other problems," he says.
By treating eight cell specimens taken from sickle cell anemia patients, the investigators discovered that attaching the ankyrin insulator to a normal beta-globin gene increases the amount of normal beta globin protein while reducing the quantity of sickled protein. "The total amount of protein stays the same, which is very important," says first author Dr. Laura Breda, pediatric research associate at Weill Cornell Medical College.
The researchers say that their advances will likely make a substantial impact on a number of fields, including gene regulation and transfer and the design of gene therapy trials. "This study represents a fresh departure from previously published work in the field of gene therapy," Dr. Rivella says.

Source: Weill Cornell Medical College