Leukemia Awareness

Mixed race donors hard to find – Michiana man needs marrow transplant

A Michiana man is asking for help from the public as he intensifies his search for a suitable bone marrow donor. Jeff Lafferty of Osceola is going to great lengths to beat the great odds he faces as a person of mixed race. On the ice, Jeff is known as “Coach” Lafferty who leads the Michiana Sting—a woman’s hockey team—into battle.

Off the ice, Jeff has been battling cancer for the past five years. “It’s a treatable form of Leukemia, which is Chronic Lymphocytic Leukemia,” he said. “In order for us to get it in remission would be the bone marrow transplant, that’s the only way I would be one hundred percent cancer free.”

The prospects would be easier if Jeff were 100-percent Caucasian. Of all the potential donors on the “Be the Match” Donor Registry, about 6 million people, or 74-percent of the total, are Caucasian. If Jeff were 100-percent Hispanic, he’d have 800-thousand potential donors waiting to help. But since Jeff is a mixture of both races, he has just 250-thousand chances to find a match through the registry. Mixed race donors make up just 3 percent of the total.

“As I looked into it, you know this became a growing problem with me being of mixed race having a Hispanic mother Caucasian father, it became a bigger issue then at that point. Knowing that there’s not a whole lot of mixed race people that are on the donor list,” Lafferty said.

It’s now Jeff’s goal to try and get more people, in general, and more people of mixed race, in particular, to sign up for the donor registry. Lafferty has organized a marrow donor drive for this Saturday in Mishawaka.

“With a growing Hispanic population here in the Michiana area, it’s a very big reason why I wanted to do this,” Lafferty said. “My goal is to save some body’s life, so if it means hopefully 40, 50 people show up, fantastic, if some body’s life is saved and only ten people who up, then that’s even better too.”

The marrow drive will take place March 27th from 10 a.m. until 4 p.m. at the Southside General Baptist Church in Mishawaka, 1615 S. Spring Street. The initial visit involves having your cheek swabbed. The process becomes more complicated if one becomes an actual donor. For more information visit: http://www.marrow.org/
A blood drive will also take place at the church from 10 a.m. until 1 p.m.

About Be The Match
Be The Match is a movement that engages a growing community of people inspired to help patients who need an unrelated marrow or umbilical cord blood transplant. The National Marrow Donor Program (NMDP), a leader in the field of marrow and cord blood transplantation, created Be The Match to provide opportunities for the public to become involved in saving the lives of people with leukemia, lymphoma and other life-threatening diseases. Volunteers can join the Be The Match Registry – the world’s largest and most diverse listing of potential marrow donors and donated cord blood units – as well as contribute financially to Be The Match Foundation or give their time. For more information, visit BeTheMatch.org or call 1 (800) MARROW-2

• What are bone marrow and hematopoietic stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells known as hematopoietic or blood-forming stem cells. (Hematopoietic stem cells are different from embryonic stem cells. Embryonic stem cells can develop into every type of cell in the body.) Hematopoietic stem cells divide to form more blood-forming stem cells, or they mature into one of three types of blood cells: White blood cells, which fight infection; red blood cells, which carry oxygen; and platelets, which help the blood to clot. Most hematopoietic stem cells are found in the bone marrow, but some cells, called peripheral blood stem cells (PBSCs), are found in the bloodstream. Blood in the umbilical cord also contains hematopoietic stem cells. Cells from any of these sources can be used in transplants.

• What are bone marrow transplantation and peripheral blood stem cell transplantation?

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:

* In autologous transplants, patients receive their own stem cells.
* In syngeneic transplants, patients receive stem cells from their identical twin.
* In allogeneic transplants, patients receive stem cells from their brother, sister, or
parent. A person who is not related to the patient (an unrelated donor) also may be used.

• Why are BMT and PBSCT used in cancer treatment?

One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.

Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patient’s bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrow’s ability to produce the blood cells the patient needs.

In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells that remain in the patient’s body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them. (A potential complication of allogeneic transplants called graft-versus-host disease is discussed in Questions 5 and 14.)

• What types of cancer are treated with BMT and PBSCT?

BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma. They are most effective when the leukemia or lymphoma is in remission (the signs and symptoms of cancer have disappeared). BMT and PBSCT are also used to treat other cancers such as neuroblastoma (cancer that arises in immature nerve cells and affects mostly infants and children) and multiple myeloma. Researchers are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment of various types of cancer.

• How are the donor’s stem cells matched to the patient’s stem cells in allogeneic or syngeneic transplantation?

To minimize potential side effects, doctors most often use transplanted stem cells that match the patient’s own stem cells as closely as possible. People have different sets of proteins, called human leukocyte-associated (HLA) antigens, on the surface of their cells. The set of proteins, called the HLA type, is identified by a special blood test.

In most cases, the success of allogeneic transplantation depends in part on how well the HLA antigens of the donor’s stem cells match those of the recipient’s stem cells. The higher the number of matching HLA antigens, the greater the chance that the patient’s body will accept the donor’s stem cells. In general, patients are less likely to develop a complication known as graft-versus-host disease (GVHD) if the stem cells of the donor and patient are closely matched. GVHD is further described in Question 14.

Close relatives, especially brothers and sisters, are more likely than unrelated people to be HLA-matched. However, only 25 to 35 percent of patients have an HLA-matched sibling. The chances of obtaining HLA-matched stem cells from an unrelated donor are slightly better, approximately 50 percent. Among unrelated donors, HLA-matching is greatly improved when the donor and recipient have the same ethnic and racial background. Although the number of donors is increasing overall, individuals from certain ethnic and racial groups still have a lower chance of finding a matching donor. Large volunteer donor registries can assist in finding an appropriate unrelated donor (see Question 19).

Because identical twins have the same genes, they have the same set of HLA antigens. As a result, the patient’s body will accept a transplant from an identical twin. However, identical twins represent a small number of all births, so syngeneic transplantation is rare.

• How is bone marrow obtained for transplantation?

The stem cells used in BMT come from the liquid center of the bone, called the marrow. In general, the procedure for obtaining bone marrow, which is called “harvesting,” is similar for all three types of BMTs (autologous, syngeneic, and allogeneic). The donor is given either general anesthesia, which puts the person to sleep during the procedure, or regional anesthesia, which causes loss of feeling below the waist. Needles are inserted through the skin over the pelvic (hip) bone or, in rare cases, the sternum (breastbone), and into the bone marrow to draw the marrow out of the bone. Harvesting the marrow takes about an hour.

The harvested bone marrow is then processed to remove blood and bone fragments. Harvested bone marrow can be combined with a preservative and frozen to keep the stem cells alive until they are needed. This technique is known as cryopreservation. Stem cells can be cryopreserved for many years.

• How are PBSCs obtained for transplantation?

The stem cells used in PBSCT come from the bloodstream. A process called apheresis or leukapheresis is used to obtain PBSCs for transplantation. For 4 or 5 days before apheresis, the donor may be given a medication to increase the number of stem cells released into the bloodstream. In apheresis, blood is removed through a large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest, or groin area). The blood goes through a machine that removes the stem cells. The blood is then returned to the donor and the collected cells are stored. Apheresis typically takes 4 to 6 hours. The stem cells are then frozen until they are given to the recipient.

• How are umbilical cord stem cells obtained for transplantation?

Stem cells also may be retrieved from umbilical cord blood. For this to occur, the mother must contact a cord blood bank before the baby’s birth. The cord blood bank may request that she complete a questionnaire and give a small blood sample.

Cord blood banks may be public or commercial. Public cord blood banks accept donations of cord blood and may provide the donated stem cells to another matched individual in their network. In contrast, commercial cord blood banks will store the cord blood for the family, in case it is needed later for the child or another family member.

After the baby is born and the umbilical cord has been cut, blood is retrieved from the umbilical cord and placenta. This process poses minimal health risk to the mother or the child. If the mother agrees, the umbilical cord blood is processed and frozen for storage by the cord blood bank. Only a small amount of blood can be retrieved from the umbilical cord and placenta, so the collected stem cells are typically used for children or small adults.

• Are any risks associated with donating bone marrow?

Because only a small amount of bone marrow is removed, donating usually does not pose any significant problems for the donor. The most serious risk associated with donating bone marrow involves the use of anesthesia during the procedure.

The area where the bone marrow was taken out may feel stiff or sore for a few days, and the donor may feel tired. Within a few weeks, the donor’s body replaces the donated marrow; however, the time required for a donor to recover varies. Some people are back to their usual routine within 2 or 3 days, while others may take up to 3 to 4 weeks to fully recover their strength.

• Are any risks associated with donating PBSCs?

Apheresis usually causes minimal discomfort. During apheresis, the person may feel lightheadedness, chills, numbness around the lips, and cramping in the hands. Unlike bone marrow donation, PBSC donation does not require anesthesia. The medication that is given to stimulate the release of stem cells from the marrow into the bloodstream may cause bone and muscle aches, headaches, fatigue, nausea, vomiting, and/or difficulty sleeping. These side effects generally stop within 2 to 3 days of the last dose of the medication.

• How does the patient receive the stem cells during the transplant?

After being treated with high-dose anticancer drugs and/or radiation, the patient receives the stem cells through an intravenous (IV) line just like a blood transfusion. This part of the transplant takes 1 to 5 hours.

• Are any special measures taken when the cancer patient is also the donor (autologous transplant)?

The stem cells used for autologous transplantation must be relatively free of cancer cells. The harvested cells can sometimes be treated before transplantation in a process known as “purging” to get rid of cancer cells. This process can remove some cancer cells from the harvested cells and minimize the chance that cancer will come back. Because purging may damage some healthy stem cells, more cells are obtained from the patient before the transplant so that enough healthy stem cells will remain after purging.

• What happens after the stem cells have been transplanted to the patient?

After entering the bloodstream, the stem cells travel to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets in a process known as “engraftment.” Engraftment usually occurs within about 2 to 4 weeks after transplantation. Doctors monitor it by checking blood counts on a frequent basis. Complete recovery of immune function takes much longer, however—up to several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic or syngeneic transplants. Doctors evaluate the results of various blood tests to confirm that new blood cells are being produced and that the cancer has not returned. Bone marrow aspiration (the removal of a small sample of bone marrow through a needle for examination under a microscope) can also help doctors determine how well the new marrow is working.

• What are the possible side effects of BMT and PBSCT?

The major risk of both treatments is an increased susceptibility to infection and bleeding as a result of the high-dose cancer treatment. Doctors may give the patient antibiotics to prevent or treat infection. They may also give the patient transfusions of platelets to prevent bleeding and red blood cells to treat anemia. Patients who undergo BMT and PBSCT may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions.

Potential long-term risks include complications of the pretransplant chemotherapy and radiation therapy, such as infertility (the inability to produce children); cataracts (clouding of the lens of the eye, which causes loss of vision); secondary (new) cancers; and damage to the liver, kidneys, lungs, and/or heart.

With allogeneic transplants, a complication known as graft-versus-host disease (GVHD) sometimes develops. GVHD occurs when white blood cells from the donor (the graft) identify cells in the patient’s body (the host) as foreign and attack them. The most commonly damaged organs are the skin, liver, and intestines. This complication can develop within a few weeks of the transplant (acute GVHD) or much later (chronic GVHD). To prevent this complication, the patient may receive medications that suppress the immune system. Additionally, the donated stem cells can be treated to remove the white blood cells that cause GVHD in a process called “T-cell depletion.” If GVHD develops, it can be very serious and is treated with steroids or other immunosuppressive agents. GVHD can be difficult to treat, but some studies suggest that patients with leukemia who develop GVHD are less likely to have the cancer come back. Clinical trials are being conducted to find ways to prevent and treat GVHD.

The likelihood and severity of complications are specific to the patient’s treatment and should be discussed with the patient’s doctor.

• What is a “mini-transplant”?

A “mini-transplant” (also called a non-myeloablative or reduced-intensity transplant) is a type of allogeneic transplant. This approach is being studied in clinical trials for the treatment of several types of cancer, including leukemia, lymphoma, multiple myeloma, and other cancers of the blood.

A mini-transplant uses lower, less toxic doses of chemotherapy and/or radiation to prepare the patient for an allogeneic transplant. The use of lower doses of anticancer drugs and radiation eliminates some, but not all, of the patient’s bone marrow. It also reduces the number of cancer cells and suppresses the patient’s immune system to prevent rejection of the transplant.

Unlike traditional BMT or PBSCT, cells from both the donor and the patient may exist in the patient’s body for some time after a mini-transplant. Once the cells from the donor begin to engraft, they may cause the graft-versus-tumor (GVT) effect and work to destroy the cancer cells that were not eliminated by the anticancer drugs and/or radiation. To boost the GVT effect, the patient may be given an injection of the donor’s white blood cells. This procedure is called a “donor lymphocyte infusion.”

• What is a “tandem transplant”?

A “tandem transplant” is a type of autologous transplant. This method is being studied in clinical trials for the treatment of several types of cancer, including multiple myeloma and germ cell cancer. During a tandem transplant, a patient receives two sequential courses of high-dose chemotherapy with stem cell transplant. Typically, the two courses are given several weeks to several months apart. Researchers hope that this method can prevent the cancer from recurring (coming back) at a later time.

• How do patients cover the cost of BMT or PBSCT?

Advances in treatment methods, including the use of PBSCT, have reduced the amount of time many patients must spend in the hospital by speeding recovery. This shorter recovery time has brought about a reduction in cost. However, because BMT and PBSCT are complicated technical procedures, they are very expensive. Many health insurance companies cover some of the costs of transplantation for certain types of cancer. Insurers may also cover a portion of the costs if special care is required when the patient returns home.

There are options for relieving the financial burden associated with BMT and PBSCT. A hospital social worker is a valuable resource in planning for these financial needs. Federal Government programs and local service organizations may also be able to help.

The National Cancer Institute’s (NCI) Cancer Information Service (CIS) can provide patients and their families with additional information about sources of financial assistance (see below).

• What are the costs of donating bone marrow, PBSCs, or umbilical cord blood?

Persons willing to donate bone marrow or PBSCs must have a sample of blood drawn to determine their HLA type. This blood test usually costs $65 to $96. The donor may be asked to pay for this blood test, or the donor center may cover part of the cost. Community groups and other organizations may also provide financial assistance. Once a donor is identified as a match for a patient, all of the costs pertaining to the retrieval of bone marrow or PBSCs is covered by the patient or the patient’s medical insurance.

A woman can donate her baby’s umbilical cord blood to public cord blood banks at no charge. However, commercial blood banks do charge varying fees to store umbilical cord blood for the private use of the patient or his or her family.

• Where can people get more information about potential donors and transplant centers?

The National Marrow Donor Program (NMDP), a federally funded nonprofit organization, was created to improve the effectiveness of the search for donors. The NMDP maintains an international registry of volunteers willing to be donors for all sources of blood stem cells used in transplantation: Bone marrow, peripheral blood, and umbilical cord blood.

The NMDP Web site contains a list of participating transplant centers at http://www.marrow.org/PATIENT/Plan_for_Tx/Choosing_a_TC/US_NMDP_Transplant_Centers/tc_list_by_state.pl

The list includes descriptions of the centers, as well as their transplant experience, survival statistics, research interests, pretransplant costs, and contact information.
Organization:     National Marrow Donor Program
Address:     Suite 100
3001 Broadway Street, NE.
Minneapolis, MN 55413–1753
Telephone     612–627–5800
1–800–627–7692 (1–800–MARROW–2)
1–888–999–6743 (Office of Patient Advocacy)
E-mail:     patientinfo@nmdp.org
Internet Web site:     http://www.marrow.org

• Where can people get more information about clinical trials of BMT and PBSCT?

Clinical trials that include BMT and PBSCT are a treatment option for some patients. Information about ongoing clinical trials is available from NCI’s Cancer Information Service (see below), or from the NCI’s Web site at http://www.cancer.gov/clinicaltrials

(source www.cancer.gov)

View and Download the Bone Marrow Transplantation Facts PDF

A critical first step for the development of safer and more effective stem cell therapies for patients with leukemia, multiple myeloma and anaemia has been taken by scientists at UC San Diego. They’ve identified the specific region in vertebrates where adult blood stem cells arise during embryonic development. The researchers say their time-lapse imaging of the process, by which primitive embryonic tissues first produce the parent stem cells that produce all adult blood cells over the life of an individual, should help guide future efforts to repair and replace this cell population for therapeutic purposes.

Current transplantation therapies rely on the infusion of donor stem cells into a patient’s bone marrow to generate new, healthy blood cells without disease. But that procedure is often risky and can result in fatal complications, due in part to “graft-versus-host disease,” in which transplanted cells react against foreign tissues of the recipient. One means of circumventing this immune rejection problem would be to generate hematopoietic stem cells, or HSCs, using the patient’s own precursor cells. Such cells would be perfectly genetically matched, but in order to generate such cells, scientists must first understand the molecular processes that underlie specification of HSCs.

“If we could generate healthy HSCs from patients and transplant them back into their own bone marrow, it would eliminate many complications,” said David Traver, who headed the research team.

“Our findings are an important step toward this goal because they provide a better understanding of how HSCs, the cell type responsible for the clinical benefits of bone marrow transplants, are first specified during development.

“This improved understanding will aid efforts to instruct pluripotent embryonic stem cells (ESCs), the stem cells that can produce all types of tissue-specific stem cells in the body, to make HSCs; something that is not currently possible. In other words, we are one step closer now to understanding how to clinically generate HSCs for cellular replacement therapies from ESCs,” he added.

Traver and his colleagues made their discoveries in zebrafish, a model laboratory organism for geneticists in which embryos are transparent, allowing the researchers to observe and track individual stem cells with a microscope.

“Using zebra-fish embryos with fluorescently labeled tissues, we were able to demonstrate that HSCs arise directly from cells lining the floor of the dorsal aorta by imaging the process in living embryos.”

The study appears in this week’s early online edition of the journal Nature. (Source-ANI RAS)

Genzyme Must Further Study the Drug for Adults

NEW YORK – Genzyme Corp. must collect more data on the leukemia drug Clolar before the Food and Drug Administration will consider expanding the use of the therapy to previously untreated adults with acute myeloid leukemia.

Based on findings from a limited trial, Genzyme sought approval to market the drug to patients with the most common form of blood and bone marrow cancer in adults, the Cambridge, Mass., company said yesterday.

The FDA recommended a randomized, controlled clinical study before it would consider expanding Clolar’s use.

Clolar is approved for children with acute lymphoblastic leukemia (a cancer in which the bone marrow makes too many white blood cells) who have relapsed or are resistant to other treatments.

Genzyme plans to request a meeting with the FDA to discuss which studies will satisfy its requirements to use the drug for untreated adults.

From the Genzyme “About” page:

One of the world’s leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 11,000 employees in locations spanning the globe and 2008 revenues of $4.6 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.

With many established products and services helping patients in nearly 100 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company’s products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme’s commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

Gainesville City Hall

Gainesville, FL – For his 18th birthday, Patrick Fitzpatrick asked for a pair of flashy track shoes for the upcoming season. For his 50th birthday, he was hoping to find a gift-wrapped ticket to the UF-Tennessee football game. For his 60th birthday, Fitzpatrick wanted to get arrested.

As a light drizzle fell on the large signs that read, “Would Jesus Feed the Homeless?,” “5th Meanest City” and “Homeless Rights are Human Rights,” near the stairs of Gainesville City Hall, Fitzpatrick and a few others broke the law Monday by handing out food to Gainesville’s homeless population. The law, passed in 2003, prohibits the noncity-sponsored distribution of food in front of City Hall.

“We’re breaking this law because we have a conscience,” said Fitzpatrick, who didn’t get his birthday wish. “I don’t care who they are — nobody can tell us who we can or can’t give a sandwich to.”

After the display of civil disobedience, Fitzpatrick, longtime homeless awareness activist, announced that he will run for the 4th District city commissioner seat, which will empty in March when its current holder, Craig Lowe, runs for mayor.

As the homeless munched peanut butter sandwiches and chocolate cake in cadence with faint, live accordion music, Fitzpatrick assured observers and reporters of the seriousness of his campaign and the need to resist the ever-growing power of current officials, who he referred to as “the robber barons.”

“The curve of politics typically goes in favor of the wealthy,” he said. “The curve of justice, however, goes to the poor.”

If elected, one of his first orders of business will be to rescind the 130-person limit on the amount of food served at the St. Francis House shelter. Fitzpatrick plans to establish a permanent place for homeless residents to stay. Danny Griggs, a Hawthorne resident who assists Fitzpatrick in caring for the homeless, believes the restrictions imposed at the St. Francis House need to be addressed immediately.

“I saw with my own eyes a pregnant woman get turned away because she happened to be No. 131,” he said. “That’s just not right.”

According to Griggs, one of the main problems contributing to Gainesville’s homeless problem is a misguided perception that all homeless residents have only themselves to blame for their circumstances.

“They’re smart people,” Griggs said, mentioning innovations made by homeless people to survive such as secretly cultivated gardens in which they grow assortments of vegetables. “Some of them just can’t do it by themselves.”

“Over there are the really stupid people,” he said, pointing to the tall buildings across from City Hall that house local businesses.

To David Wayne, who has been homeless for the past four months, the issue isn’t about politics or winning elections — it’s about getting the next meal. Wayne, whose battle with leukemia made his face jerk and contort as he speaks, sleeps near the courthouse. But despite his problems, Wayne said the efforts of homeless advocates like Fitzpatrick give him hope.

“You won’t see worry in my eyes; I got a secret,” he said, pointing to the sky. “My secret is God.”  (Source www.alligator.org)

Gainesville is the largest city and county seat of Alachua County. It serves as the cultural, educational and commercial center for the North Central Florida Region.

Positive Attitude Works Miracles

(recent  post by a person with Lupus featured on The Gazette)

In 2007, I was diagnosed with lupus and Lyme disease, and before getting sick, I would have never believed a positive attitude helped “cure” an illness. Then I got sick and brought my unhappy/negative attitude with me. No matter what medications I took, I was not getting well.

I’ve known many people with illness, some as serious as leukemia. Some are in remission, some have died. The ones who are well are the ones who had a positive attitude, the ones who died are the ones who held on to anger. I started to get better when I changed my attitude. I’m still not 100 per cent and I am still working on my happiness, but, in the meantime, I’m close to being fully functional again. And out of the ashes, I was lucky enough to find my passion in natural healing. I’m now working on my naturopathic degree in hopes of sharing my message and to help others who are ill. Anyone who took a human anatomy and physiology course would understand there is a definite connection between mind and body.

Researchers have discovered that by enriching a class of blood stem cells they can inhibit the growth of a rare but aggressive form of leukemia.

Dr. Yaacov Ben-David, a senior scientist at Sunnybrook Research Institute, and colleagues found that the presence of leukemic inhibitory stem cells in the spleens of a mouse model slows the advance of erythroleukemia, a cancer in which a large number of abnormal red blood cells grow in the blood and bone marrow. Prognosis for patients with this type of leukemia is poor.

With this discovery, scientists have a new model for the development of a more efficient drug therapy for this and other forms of leukemia. It also suggests a route for a novel combination therapy, one that targets both genes and cells.

“Many scientists are using targeted therapy for genes that activate or control the growth of cancer cells,” says Ben-David, who is also a professor at the University of Toronto. “But the cellular environment around the tumour, its microenvironment, is the body’s first defence. If we can first strengthen it by the enrichment of inhibitory stem cells, then we may have a better treatment for patients than with targeted therapy alone.”

For their study, the researchers turned to a mouse model of a noncancerous blood disorder, in which the bone marrow makes too many red blood cells. With this condition, despite having an abnormally high number of blood cells, these mice rarely develop erythroleukemia. The researchers thus hypothesized that the inhibitory stem cells have a protective effect. To test their hypothesis, the scientists induced erythroleukemia in mouse models with this noncancerous blood disorder. Upon analysis, they found that the ability of the leukemic inhibitory stem cells to secrete nitric oxide was primarily responsible for the cells’ anti-tumour properties. They also discovered that specific cytokines, signalling molecules that tell cells how to communicate with each other, enriched the stem cells, strengthening the anti-tumour effect.

“I’m very excited about this work,” says Ben-David, whose lab was the first to show, in 2004, that two proteins in the micro-environment of the spleen hasten the growth of leukemic cells, and that removal of the spleen might therefore be a way to halt the spread of leukemia, an approach now being clinically tested at Sunnybrook. Now that we’ve identified a molecular mechanism preclinically, we can look at performing a clinical trial in the near future,” he says.

Erythroleukemia typically affects people aged over 50 years old, though it affects all age groups, including children, and more men than women get it. Risk factors include prior exposure to chemicals, including chemotherapy to treat cancer. (research was supported by the Canadian Institutes of Health Research).

Please Promote Leukemia Awareness Wherever You Can

Cancer researchers at the Stanford University School of Medicine have discovered a promising new chemotherapy target for a deadly form of leukemia. Their discovery hinges on a novel double agent role for a molecular signal that regulates cell growth. The rogue signal, glycogen synthase kinase 3, was previously found to halt uncontrolled cell growth, preventing several forms of cancer. It also keeps growth of healthy cells in check. But new data show that GSK3 fuels a deadly form of white blood cell cancer, which accounts for five to 10 percent of child and adult leukemias and more than three-quarters of leukemias diagnosed in infants.

This finding was quite unexpected, said Michael Cleary, MD, senior author of a paper describing the discovery. GSK3 has never been implicated in promoting cancer. Cleary is a professor of pathology and of pediatrics and a member of the Stanford Cancer Center. The research will appear online in Nature on Sept. 17. Clearys team discovered that inhibiting GSK3 combats leukemias caused by mutated MLL genes. MLL, an acronym for mixed-lineage leukemia, refers to an unusual feature of these deadly cancers. Most leukemias begin in just one of the bodys two white blood cell factories, either the lymph nodes or the bone marrow. But in mixed-lineage leukemias, the bad cells can show markers from both kinds of tissue.

Newly diagnosed leukemia patients have their cancer cells tested to see which genes are driving the cancer. Mutated MLL genes are viewed as a bad prognostic marker, Cleary said. There is intense interest in coming up with better ways to treat these patients, he said. Clearys findings indicate GSK3 may be an effective target for future leukemia drugs.

The first hint of GSK3s role came from petri-dish tests on cancer cells. Postdoctoral scholar Zhong Wang, PhD, treated dishes of different kinds of cancer cells with a battery of chemicals that inhibit various cell signals. When a GSK3 inhibitor clobbered cells with mutant MLL genes, Wang realized his work was cut out for him. I was excited, but I knew I would have to do lots of work to confirm the finding, he said. Most people say GSK3 cannot be a cancer target. That is because of earlier discoveries that showed GSK3 slowed malignancies such as colon cancer.

But Wangs extensive follow-up experiments confirmed GSK3 drove leukemia. For instance, he gave the psychiatric drug lithium, a weak GSK3 inhibitor, to mice with MLL-gene leukemia. Mice that got lithium lived longer than those that did not. Now that the team knows GSK3 is a potential anti-leukemia target, they are studying how the signal revs up cancer.

They are also starting the hunt for high-potency GSK3 inhibitors that could safely be given to humans. The signal is an especially promising leukemia drug target, the researchers said, because GSK3 normally slows the growth of healthy bone marrow stem cells. Thus, it is possible that giving GSK3 inhibitors will have a double-whammy effect on leukemia, killing the cancerous white blood cells and promoting growth of healthy stem cells, such as those given in a bone marrow transplant.

Most current cancer drugs target both the normal and the aberrant cells, Cleary said. It would be a big advantage in cancer treatment if a drug were developed that could selectively kill cancer but help healthy cells grow. Of course, the danger with GSK3 inhibitors would be that they might also cause other cancers if given long-term. Cleary said it is too early to tell if or how a new drug might skirt that problem. There will be a lot of hard work required to get better anti-GSK3 compounds, test them in preclinical models and translate them to human trials, he said. Cleary and Wangs team at Stanford included Kevin Smith, PhD, research associate in pathology, and postdoctoral scholars Mark Murphy, PhD; Obdulio Piloto, PhD; and Tim Somervaille, MD, PhD. The research was supported by grants from the Children™s Health Initiative of the Lucile Packard Foundation for Childrens Health, the Public Health Service, the Leukemia and Lymphoma Society, the Williams Lawrence Foundation and the Stanford Cancer Center. (source mednews.stanford.edu)

New targeted therapy finds and eliminates deadly leukemia stem cells

New research describes a molecular tool that shows great promise as a therapeutic for human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer. The study, published by Cell Press in the July 2nd issue of the journal Cell Stem Cell, describes exciting preclinical studies in which a new therapeutic approach selectively attacks human cancer cells grown in the lab and in animal models of leukemia.

According to a press release issued by EurekAlert, AML is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy. “The cellular and molecular basis for this dismal picture is unclear,” offers senior study author Associate Professor Richard Lock from the Children’s Cancer Institute Australia and the University of New South Wales. “However, previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance.” LSCs are cells that can initiate AML and are critical for its long-term growth.

Associate Professor Lock and colleagues exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells. CD123 is part of the interleukin-3 receptor, a protein that interacts with a growth factor (called a cytokine) that influences cell survival and proliferation. The researchers created a therapeutic antibody that recognized and bound to CD123 with the hope that this antibody would selectively interfere with AML-LSC survival.

When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signaling in the tumor cells was blocked. Further, 7G3 impaired migration of the AML-LSCs to bone marrow and activated the innate immune system of the host mouse to destroy the AML-LSCs. Overall, treatment with 7G3 substantially improved mouse survival when compared with control groups. The researchers go on to report that a CD123-targeting antibody is currently being used in phase 1 clinical trials of advanced AML and that there are no signs of treatment-related toxicity.

These results hold substantial promise for future cancer therapeutics. “The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials,” concludes Associate Professor Lock. (as reported by “The Hindu”)

BOSTON (Reuters) – Children can be treated for a common form of childhood leukemia without bombarding the brain with radiation, reducing the risk that they will suffer additional tumours and thinking problems, U.S. researchers said on Wednesday.

They said chemotherapy injected into the blood and the fluid that bathes the brain and spinal cord produced results that were just as good.

“We believe children with ALL (acute lymphoblastic leukemia) do not need to get cranial irradiation preventively, which is different from what some centers recommend,” Mary Relling of St. Jude Children’s Research Hospital in Memphis, who worked on the study published in the New England Journal of Medicine.

Radiation was once a routine therapy for acute lymphoblastic leukemia, the most common form of childhood cancer. It is still given to 20 percent of the 3,400 youngsters in the United States who are diagnosed with ALL each year in the hopes of preventing a relapse.

But the treatment can cause second cancers, stunted growth, hormone imbalances and cognitive deficits.

In the new study, Relling and colleagues found 86 percent of the 498 children given aggressive chemotherapy survived, cancer-free, for five years.

Among 71 patients who normally would have received brain irradiation in the past, the five-year survival rate was 91 percent, much better than a comparison group consisting of children who had previously received the radiation therapy for their ALL. For them, the survival rate was 73 percent.

“These are the best results reported to date,” Relling said.

The amount of chemotherapy was personalized for each child, depending in part on how many leukemia cells were detected after initial treatment.

Relling said that in the 1960s, radiation offered a big advantage in survival at a time when only 20 percent or fewer lived for five years, in part because new tumours would appear in the central nervous system. Using radiation increased the survival rate to 50 percent.

“That was a very dramatic increase in cure rates, so there was a time where almost every patient with childhood leukemia would get irradiation,” she said.

“Then there was a gradual backing away from that,” so only children in the highest-risk group got it, where the risk of recurrence outweighed the risk of serious side effects.

Acute lymphoblastic leukemia is a cancer of the white blood cells, the cells in the body that normally fight infections.