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Mon, Sep 9 10:00am · New genetic test classifies lymphomas in Hematology

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The current diagnostic tools in a pathologist’s arsenal sometimes cannot provide a clear distinction between primary mediastinal large B-cell lymphoma (one of the few lymphomas more common in younger women) and diffuse large B-cell lymphoma, the most common type of non-Hodgkin’s lymphoma overall. This may occasionally give rise to diagnostic inaccuracy in routine practice and could leave physicians guessing as to the best course of therapy for their patients.

On April 18, a team of researchers led by Lisa Rimsza, M.D., a pathologist and director of the Mayo Clinic Molecular Diagnostics – Arizona Laboratory launched a new genetic test, the Lymph3Cx, which distinguishes between the two types of lymphoma. The establishment of the test and their study results were published in the journal Blood.

Having a test like this available in a clinical laboratory setting can help physicians, determine the correct classification of lymphoma to improve therapeutic decision-making for patient care. The test can also be used as a tool to support clinical trials. Read the rest of the article on Discovery’s Edge.

Are you, or a loved one, living with lymphoma and would like to meet others? Explore some of the following discussions taking place in the Blood Cancers & Disorders group on Connect:

Tue, Jul 23 11:00am · Helping Others Heal: CAR-T vs. Cancer in Hematology

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At first, Tanis Milicevic’s local doctor told her to wait and see. Pregnant with her second child, Tanis had been sensitive about changes in her body when she felt a worrisome bump on the back of her head.

The doctor’s advice gave her temporary peace — the bump was small and she could just monitor it. Then, after her baby’s first birthday, Tanis felt a lump in her underarm.

“That’s when I knew that something was not right,” she says. Although she otherwise felt fine, her instincts about her health were correct. A biopsy showed she had non-Hodgkin’s lymphoma.

Tanis and her husband, Marko, learned that while her disease was slow growing at this stage, it would also be hard to cure. “It was a difficult pill to swallow, but we remained optimistic. You live life and push forward,” Marko says. They had to for their sons, 1-year-old Jonathon and 8-year-old Max.

Tanis, then 44, underwent radiation and then chemotherapy for two years. The treatments kept the cancer in remission for five years. It freed her to focus on her family and her business, a women’s contemporary fashion boutique. When the cancer returned, Tanis came to Mayo Clinic.

Read the rest of Tanis’ story in Mayo Magazine.

Connect with others talking about CAR-T cell therapy and non-Hodgkin’s lymphoma in the following groups and discussions:

Fri, Jun 28 9:00am · Dr. Robert Kyle: On living a full life of medical (and stamp collecting) achievements in Hematology

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From a one-room country school in North Dakota to worldwide recognition as a pioneer in multiple myeloma, Mayo Clinic hematologist Robert Kyle, M.D., shares his extraordinary, full life.

Robert Kyle, M.D., was heading toward a career in forestry until “a family friend suggested he become a doctor.” He kept that thought “in the back of his mind” until his brother was diagnosed with meningococcal meningitis. Then it shifted a bit closer to the front of his thinking.

“His doctor impressed me, and that experience further increased my interest in medicine,” Dr. Kyle tells Jame Abraham, M.D., who wrote a story on Dr. Kyle for the American Society of Clinical Oncology Post. The piece is aptly titled “Living a Full Life” and traces Dr. Kyle’s full life from his early days in “a one-room country school” in his hometown of Bottineau, North Dakota, in the 1930s and ’40s to his storied career as a Mayo Clinic hematologist.

After graduating from Northwestern University Medical School in Chicago in 1952, Dr. Kyle began an internship at Evanston Hospital, which ultimately led him to Mayo Clinic. “A couple of very impressive members of the faculty had trained at the Mayo Clinic, so I applied there and was accepted,” he tells Dr. Abraham. “The program required six months of laboratory work. One of the options was hematology, something I knew little about, so I signed up.”

And he’s never looked back. Dr. Kyle tells Dr. Abraham that, after a two-year stint at Tufts University, “I came back (to Mayo Clinic) in August 1961 and have been here ever since.”

In those 58 years, Dr. Kyle has gone on to make quite a name for himself in the field of medicine, becoming a “multiple myeloma pioneer whose groundbreaking work,” Dr. Abraham writes, “changed the practice of hematology.” So much so that it earned Dr. Kyle the distinct honor of being one of only two people to receive both the David A. Karnofsky Memorial Award from the American Society of Clinical Oncology and the Wallace H. Coulter Award from the American Society of Hematology — “the highest honors bestowed by these two groups,” according to the Post.

Find a passion outside of the clinic. I’ve found mine, but it’s an individual choice, and sometimes you just fall into something.

Despite decades of accolades, Dr. Kyle has stayed grounded and engaged in his work, and offers a bit of advice to others who don’t yet have 58 years of experience.

“You need to get away from the challenges of cancer care or you can face burnout,” he says. “Find a passion outside of the clinic. I’ve found mine, but it’s an individual choice, and sometimes you just fall into something.”

Like Dr. Kyle did after landing in the hospital for 39 days after tweaking his back during a patient exam in 1965. “I had had a passing interest in stamps, so I decided to explore stamp collecting more closely,” he tells Dr. Abraham. “I reviewed the multiple volumes of the Scott stamp catalogs, which have every stamp from every country in the world. I took it to another level and wrote a number of papers on blood transfusion as well as cancer and stamps.” (Of course he did.)

Although he no longer sees patients, Dr. Kyle continues to contribute to “the great field of multiple myeloma, Waldenstrom’s macroglobulinemia, and amyloidosis.” It’s something, he tells the Post, he’s still excited about after nearly six decades.

“The bottom line for success in medicine and research is to maintain your interest and passion about what you do,” he says.

You can read more about how Dr. Kyle’s gone about “living a full life” here and here.

This story originally appeared on the In the Loop blog. You can find it there.

Want to meet other people talking about living with Blood Cancers & Disorders? Check out some of the following discussions and meet others like you:

Wed, Feb 20 9:29am · CAR-T cell Therapy: What is it and what does it treat? in Hematology

Mayo Clinic’s CAR-T Cell Therapy Program offers a new cancer immunotherapy that involves genetically modifying T cells to activate the immune system to recognize and destroy certain cancers.

Mayo Clinic hematologist, Dr. Yi Lin, explains what chimeric antigen receptor T-cell therapy (CAR-T cell therapy) is and what types of cancers it can be used to treat. Currently CAR-T cell therapy can be used to treat two types of cancer:

  1. B-cell ALL (acute lymphocytic leukemia) for pediatric children up to 25-year-old adults
  2. Adults with B-cell non-Hodgkin lymphoma

Want to talk with others who have experience with blood cancers and disorders as well as CAR-T cell therapy? Join the discussion in the following Connect discussion groups:

Fri, Jan 25 12:14pm · ‘Almost Like You Won the Lottery’: CAR-T Cell Therapy Gives Cancer Patients New Hope in Hematology

1_25_19_HopeImagine if you could “re-train” the body’s immune system to attack and kill a very specific target. That’s essentially how Mohamed Kharfan Dabaja, M.D., director of the blood and marrow transplant and cellular therapies programs at Mayo Clinic’s Florida campus, would like you to think about CAR-T cell therapy. For some people with blood cancer, the treatment can offer hope “where other treatments have failed,” according to First Coast News(In the Loop the original poster)

That was certainly the case for Tanis Milicevic, whom Florida’s First Coast News reports began her fight against non-Hodgkin’s lymphoma 10 years ago. Treatment provided a few years of relief and remission. But when the cancer came back, so did Tanis’s original fears. “I wanted to see them be successful and grow up,” she tells First Coast News of her two young sons. “A big concern as a mother is just leaving my husband, like how would he be able to handle all that.”

With that fear and driving motivation front of mind, Tanis made an appointment at Mayo Clinic. Under the care of Dr. Kharfan Dabaja, Tanis went through an extensive evaluation process to determine whether the innovative and individualized cell-based therapy had the potential to help her, First Coast News reports. When tests indicated it would, Tanis’s care team began the “intricate process” of collecting some of her white blood cells and sending them to a lab, where they would be genetically modified and trained to become soldiers of war against her non-Hodgkin’s lymphoma, the news station reports.

When the cells were returned to Mayo Clinic to be infused back into Tanis’s body by IV, they had been armed with “special receptors called chimeric antigen receptors, or CARs,” First Coast News reports. Amazingly, those receptors gave the cells the newfound ability to not just “recognize an antigen (or marker) at the surface of cancer cells,” but to also actively seek them out and kill them.

The result was a success for Mayo’s CAR-T cell therapy program and, more importantly, for Tanis, who was the first patient to receive CAR-T cell therapy at Mayo’s Florida campus. “Here she is over three months later with no evidence of any lymphoma in her body,” Dr. Kharfan Dabaja tells First Coast News. “There is no evidence of any disease.”

Tanis says that although “the recovery was difficult,” it was worth it. “It was almost like you won the lottery, like here is your chance at life,” she tells First Coast News. “Really you can’t even put into words that moment.”

You can read more of Tanis’s story here and read more about Mayo’s CAR-T Cell therapy program here. Discover more patient stories on In the Loop.

Meet Mayo Clinic Connect members talking about CAR-T Therapy treatment in the CAR-T Cell Therapy Group.

Thu, Jan 3 1:45pm · Mayo Clinic researchers identify new strategies that may improve CAR-T cell therapy in Hematology

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Mayo Clinic researchers have developed two new strategies that may improve the performance of chimeric antigen receptor therapy (CAR-T cell therapy) in treating cancer. They are presenting results of their preclinical research at the 2018 annual meeting of the American Society of Hematology in San Diego.

Reducing toxicity in CAR-T cell therapy

“While CAR-T cell therapy has proven successful in treating certain cancers, severe toxicities have limited its widespread application,” says Rosalie Sterner, an M.D.-Ph.D. student working in the T Cell Engineering Laboratory of Saad Kenderian, M.B. Ch.B., a Mayo Clinic hematologist. Sterner says toxicities associated with CAR-T cell therapy include cytokine release syndrome, in which patients can experience fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing and neurotoxicity.

Sterner says some patients undergoing CAR-T cell therapy get sick during treatment and require a stay in an ICU. She also notes that deaths related to the side effects of CAR-T cell therapy have been reported. Sterner and her colleagues developed a strategy to reduce the severe toxicities associated with CAR-T cell therapy.

The strategy involves blocking the GM-CSF protein, which is produced by CAR-T cells and other cells using a clinical-grade antibody (lenzilumab).

“When we blocked the GM-CSF protein, we found that we could reduce toxicities in preclinical models, says Sterner. “We also were able to demonstrate that CAR-T cells worked better after the GM-CSF protein was blocked.”

Next, researchers used a gene editing technology, called CRISPR, to generate CAR-T cells that did not secrete the GM-CSF protein. Sterner says these modified CART cells were more effective than regular CAR-T cells.

Based on their findings, the research team is proceeding with a phase II clinical trial of the GM-CSF blocking antibody during CAR-T cell therapy. If the trial results are consistent with earlier findings, the therapy could become a standard of care during CAR-T cell therapy at Mayo Clinic.

This research also is published in Blood.

Improving response rates for CAR-T cell therapy in B cell lymphoma

“In CAR-T cell therapy, physicians remove and modify a patient’s T cells to recognize and fight cancer,” says Reona Sakemura, M.D., Ph.D., a hematologist and a postdoctoral fellow in Dr. Kenderian’s laboratory. “Once modified T cells are reinfused into the patient where they seek out and ultimately kill cancer cells.”

Dr. Sakemura says response rates for CAR-T cell therapy vary by disease. For example, in B cell acute lymphoblastic leukemia, response rates of more 90 percent have been seen, compared to response rates of 10 to 30 percent for treatment with conventional chemotherapy. In other blood cancers, such as lymphoma and chronic lymphocytic leukemia, the response rates for treatment with CAR-T cell therapy remain low.

To improve the effectiveness of CAR-T cell therapy in these cancers, Dr. Sakemura and his colleagues developed a strategy to combine CAR-T cell therapy with a drug that targets a protein called “AXL.” This protein is present on the cancer and within the cancer’s environment. The drug, called “TP-0903,” not only kills cancer cells, but also it enhances the potency of CAR-T cells in attacking cancer cells and potentially lowers the toxicity associated with CAR-T cell treatment.

While more research and clinical trials are needed, Dr. Sakemura says, “We believe the latter effect may eventually be utilized as an innovative approach to augment the efficacy of CAR-T cell therapy and extend its use to other B cell cancers.”

Original story from Mayo Clinic News Network by Joe Dangor

Meet Mayo Clinic Connect members talking about CAR-T treatment in the CAR-T cell Therapy Group

Dec 14, 2018 · Immunotherapy to fight cancer: Dual-immunomodulation in Hematology

Cancer cells have learned and evolved to display a protein on their surface that sends a negative stopping signal to our immune system, halting our immune system from activating and recognizing the cancer cells.

Immunotherapy tries to induce our immune system to recognize and kill the cancer by blocking cancer cells from highjacking that checkpoint mechanism. These drugs are known as checkpoint inhibitors. They act by interfering with the cascade of signals sent by the cancer cell and liberate the immune cells for a successful anti-cancer attack.

Our immune system, especially when faced with cancer cells, can experience what is called immune cell exhaustion. Immune cells become so tired of seeing cancer cells around that they essentially get used to them and give up. This is why introducing only a checkpoint inhibitor will not work. The immune system is still too weak to activate.

What happens when immunotherapy does not work because our immune system is too weak to activate?

Mayo Clinic researchers are combining a checkpoint inhibitor to bypass the negative signal from the cancer cell and another drug to give the immune system a boost to strengthen our response.

“What we are trying to do is to block the signal from the cancer cell, and at the same time give a second positive signal that pushes our immune cells to activate,” says hematologist J. C. Villasboas, M.D. 3704053_0008

“Because we are now trying to modulate two different signals, both the negative (inhibitor) and positive signals, we are calling this therapy a dual-immunomodulatorytherapy.”

According to Dr. Villasboas, this is the first big study where these two drugs are being combined to fight aggressive lymphomas that otherwise have not responded to conventional treatments.

Although the current study is looking specifically at the effectiveness in patients with aggressive B cell non-Hodgkin’s lymphoma, the implications could be vast.

“This study on dual-immunomodulation, if effective, could be a launching point for treating many different types of cancers,” says Dr. Villasboas. “It could be revolutionary in cancer treatment and it is very exciting.”

Meet Mayo Clinic Connect members talking about living with Blood Cancers & Disorders and share your experiences or concerns in the member-to-member support group:

Dec 6, 2018 · Immunotherapy to fight cancer: What is it and how does it work? in Hematology

Let’s start by refreshing our understanding of how our immune system works (in case you can’t recall your high school biology course in perfect detail).

Our immune system fights invaders, such as germs, throughout our body. Another important function of our immune system is to recognize and destroy cancer cells that may form within our body. Our immune system naturally gets weak, or tired, as we age. Additionally, cancer cells can develop an ability to hide from the immune system, or can disable the immune system from acting against them. Combine a tired immune system with a cancer that turns it off (or hides from it), and the result can be particularly troubling for the older population.

The goal of immunotherapy for cancer is to induce our immune system to recognize and kill cancer cells. Over the past few decades, immunotherapy has become an important part of treating some types of cancer.

How our immune system is activated and how cancer cells have found a way around our immune system:

  • When our immune system sees something foreign, it receives a series of signals
    • + Signal 1 – get ready
    • + Signal 2 – confirms threat and activates the immune system to attack
    • – Signal – a negative signal (also known as a checkpoint) is sent to indicate the harmful entity has been controlled and it is time to shut off
  • Cancer cells have evolved to display a protein on their surface that sends the negative signal to the immune system, preventing it from activating and eliminating the cancer cells

Immunotherapy tries to induce our immune system to recognize and kill the cancer cells by introducing a checkpoint inhibitor. Checkpoint inhibitors are drugs that interfere with the cascade of signals sent by the cancer cell to deactivate the immune system.

“What we are trying to do is to block the signal from the cancer cell so that our immune system activates as it normally would,” says hematologist J.C. Villasboas, M.D. 12_6_18_Villasboas

“Immunotherapy has been a homerun for classic Hodgkin’s lymphoma,” says Dr. Villasboas. “But the other 90 percent of lymphomas have had limited activity when treated with checkpoint inhibitors alone.”

Coming up next, we will look in to what happens when checkpoint inhibitors alone are not enough to activate our immune system. Dr. Villasboas and Dr. Stephen Ansell are on the forefront of research in dual-immunomodulation, a technique that combines both checkpoint inhibitors and immune system accelerants. Discover opportunities and learn more about Clinical Trials at Mayo Clinic.

Meet Mayo Clinic Connect members talking about living with Blood Cancers & Disorders and share your experiences or concerns in the member-to-member support group.