CAR-T- therapy safe and effective for leukemia

Results of the global, multicenter, pivotal phase 2 study that led to the first FDA approval of a gene therapy/cell therapy approach known as CAR T-cell therapy. The therapy, tisagenlecleucel, uses a patient's own white blood cells that have been genetically re-engineered to specifically target and kill cancer cells. It was approved to treat pediatric acute lymphoblastic leukemia (ALL), the most common childhood cancer. Senior authors on the study include Stephan A. Grupp, MD, PhD, of Children's Hospital of Philadelphia and Michael A. Pulsipher, MD, of Children's Hospital Los Angeles (CHLA).

 Researchers evaluate 75 patients between 3 to 21 years of age with relapsed or treatment refractory B-cell ALL. 61% of these patients had relapsed after allogeneic hematopoietic stem cell transplantation, an intensive therapy intended to be curative and whose failure leaves few remaining options. For comparison, the paper cites another FDA-approved therapy for the treatment of children with relapsed or refractory ALL; it produced a response rate of 20% with a median overall survival time of 13 weeks.

Patients who relapsed after transplant or did not respond to treatment - there wasn't much else we had to offer them and often, they went to hospice. Now, instead of sending them to hospice - we treat them with CAR-T-cells, make them better, then send them home. The updated analysis showed an overall remission rate of 81% within 3 months of treatment. All patients who responded to therapy showed no minimal residual disease by flow cytometry - the most sensitive means of analysis.

Overall survival was 90% at 6 months and 76% at 12 months. The median length of remission was not reached, with tisagenlecleucel remaining in the blood for up to 20 months. CAR-T therapy is truly a game changer for pediatric leukemia. Substantial side effects are associated with this therapy; grade 3 or 4 adverse events that may have been related to the therapy occurred in 73% of patients. The most significant side effects included cytokine release syndrome, often requiring admission to an intensive care unit, and neurological events in 40% of
patients.
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Effects of obesity on bone marrow cells

According to new research, obesity causes durable and harmful changes to the hematopoietic stem cell compartment-the blood-making factory in human body. Blood stem cell compartment is made up of numerous cell subsets, age and environmental stresses can lessen the healthy diversity of cells in human blood-making machinery. This can include skewing blood cell formation toward myeloid cells and possibly promoting pre-leukemic fates.

Obesity related stresses alter the cellular architecture of the hematopoietic stem cell compartment and reduce its long-term functional fitness. Tests in obese mice show these effects are progressive and that some of the harmful manifestations persist even after researchers normalize the animals' weight through dietary controls. Alterations of the body's blood-making system appear to be linked to over- expression of a transcription factor called Gfi1- a regulatory gene that controls other genes. The researchers show that oxidative stresses in the body caused by obesity drive overexpression of Gfi1.

 This produces a lasting alteration of hematopoietic stem cell compartment and molecular mayhem. The study also provides groundwork to investigate how lifestyle choices, such as diet, can durably impact blood formation and may contribute to the development of blood cancer. Hematopoietic stem cells are an important tool for treating leukemia and other blood diseases.
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How weather increases the risk of cancer

Living in a cold climate could make people more likely to get cancer, people are at greater risk in colder countries because of their genes. The same genes which stop human cells from dying in freezing temperatures are also linked to breast and bowel cancer and leukaemia. A researcher says the genes contributing to cooler climates are the same which increase the risk of malignant tumours forming in the body.

Genetic variants found to be beneficial in extreme environments, can also predispose for cancer. Cell resistance at low temperatures and at high altitude probably increases the probability for malignancy.’Previous research from 2010 found grim weather in northern parts of the world may make men more vulnerable to prostate cancer, perhaps due to a lack of vitamin D from the sun.

However the new study - which compared international rates of cancer with 240 genetic studies of cancer and seven others in cold and high-altitude countries - suggests where people live affects their genes.Extreme cold weather can cause human cells to die, so that people in freezing countries have genetic mutations to prevent cell death and repair DNA.
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Blood cancer gene could prevents heart failure

Coronary heart disease is the leading cause of death across the globe. Most of these deaths are caused by a heart attack-myocardial infarction where the blood flow to the heart is acutely blocked causing irreversible damage to the heart muscle.

People may survive a heart attack, but the damage that has occurred to the heart muscle can develop to heart failure – a debilitating condition in which the heart cannot pump blood around the body.

The gene Runx1 increases in damaged heart muscle after a heart attack. Mice with a limited capacity to increase Runx1 gene activation were protected against the adverse changes that lead to heart failure.

The Runx1 gene has been extensively studied in the context of its role in leukaemia and normal blood cell development, however until now its role in the heart was unknown.
Now researchers believe that the increased expression of the Runx1 gene, which happens after a heart attack, contributes to adverse changes in the shape and pumping action of the heart.
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Kymriah for treating acute lymphoblastic leukemia

Kymriah (tisagenlecleucel) suspension for intravenous infusion, it is a prescription cancer treatment used in patients up to 25 years old who have acute lymphoblastic leukemia (ALL) that is either relapsing or refractory.

 Kymriah is made from your white blood cells, your healthcare provider has to take some of your blood called leukapheresis. Your blood cells are frozen and sent to the manufacturing site to make Kymriah.

 Your healthcare provider may give you chemotherapy for a few days to prepare your body. When your body is ready, your healthcare provider will give you Kymriah. The drug can increase the risk of life-threatening infections that may lead to death.

Having Kymriah in your blood may cause a false-positive HIV test result by some commercial tests. Kymriah may cause side effects that are life-threatening like: difficulty breathing, fever, shaking chills, confusion, severe nausea, vomiting, diarrhea, severe muscle or joint pain, very low blood pressure and dizziness.
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Besponsa for treatment of acute lymphoblastic leukemia

Food and Drug Administration approved Besponsa for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. ALL.

B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell.

Besponsa is a targeted therapy that is thought to work by binding to B-cell ALL cancer cells that express the CD22 antigen, blocking the growth of cancerous cells.

Women who are pregnant or breastfeeding should not take Besponsa because it may cause harm to a developing fetus or a newborn baby.

Side effects of Besponsa include low levels of platelets, low levels of certain white blood cells, infection, low levels of red blood cells, fatigue, severe bleeding, fever, nausea, headache, low levels of white blood cells with fever, liver damage, abdominal pain, high levels of bilirubin in the blood,
decrease in blood cell and platelet production, infusion-related reactions and problems with the heart’s electrical pulses.
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Idhifa drug for treatment of acute myeloid leukemia

The U.S. Food and Drug Administration has approved Idhifa (enasidenib), an isocitrate dehydrogenase-2 inhibitor for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

Idhifa is a prescription medicine used to treat people with acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation whose disease has come back or has not improved after first treatment.

Enasidenib is an active ingredient in Idhifa while the inactive ingredients are: colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose acetate succinate, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium lauryl sulfate, sodium starch glycolate, talc and titanium dioxide

The drug may cause serious side effects like:nausea, vomiting, diarrhea, jaundice and lack of appetite.
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Cancer cells suppress the immune system

Human immune systems prevents different diseases including cancer, for cancer to spread and multiply, they must find a way to avoid the body's immune system.

Degenerated cells in the body cause an inflammatory reaction and influence other blood cells to the extent that the immune system is suppressed.

Tumor cells influence their environment in order to avoid an immune response and to facilitate their growth. Solid tumors manipulate macrophages of the immune system.

The relationship between leukemia cells and monocytes becomes a catalyst for cancer development. Programmed death-ligand 1PD-L1 also known as cluster receptor occurs more frequently on the surface of these nourishing cells, and suppresses the immune response for cancer to grow.

The immune response is suppressed so much that the cancer cells can multiply without any hindrance. The monocytes send out semiochemicals, which belong to the inflammation response of the immune system and support the growth and multiplication of the cancer cells.

Scientists treated monocytes and macrophages of humans and mice with suspect exosomes, as well as purified Y RNA from those exosomes, in a culture dish. In both cases, the cells changed similarly to how they would in chronic lymphatic leukemia CLL patients.

They carry more PD-L1 receptors to their surface and emit semiochemicals that accelerate the immune response and create favorable growth conditions for leukemia cells.

Adding Toll-like receptors TLR inhibitors such as Chloroquin, a medication used for malaria and rheumatic inflammation can inhibit YRNA.

CLL cells was able to suppress the reproduction of cancer cells markedly.
This makes Chloroquin a good substance for a combination therapy along with other agents for cancer treatment.
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Impacts of proteins on immune system

Different genetic make-up can impact on the activity of the immune system and our ability to fight cancer.

Proteins are made up of thousands of smaller units called amino acids, which are attached to one another in long chains.

Proteins do most of the work in cells and are required for the structure, function, and regulation of the body's tissues and organs.

 A protein called ULBP6 leads to the removal of damaged cells. There are two types of this protein found in different people.

The ULBP6 protein is found on the surface of damaged cells, including several types of cancer cells, and acts as a signal to white cells in our immune system that the damaged cell should be killed.

There are two major types of protein in the population and people who inherit a certain subtype have been shown to have a poor outcome after stem cell transplantation, a procedure used to treat leukemia, which is commonly referred to as bone marrow treatment.

The two types of ULBP6 differ only by two amino acids out of a total of around 180 and it has important influence on patient outcomes. One form of ULBP6
 forms a very strong bond indeed with its receptor NKG2D on the immune system.

This shows why transplants work less well in some people, which is an important step on the path to developing better transplant therapy for more people living with blood cancer.

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Sepsis sieve can save your life

Sepsis occurs  when an infection like blood poisoning sparks a violent immune response in which the body attacks its own organs.

Antibiotics can control the infection if it is discovered early to avoid spreading to different parts of the body. A machine that 'sieves' the blood could save people sepsis infections.

The device has been created by a British scientist, it works like a dialysis, the
blood is removed – but in this case it is cleaned of dangerous microbes using magnets.

The machine is to undergo the first human clinical trials next year and is also being tested for use against blood-borne diseases such as malaria and leukaemia.

Designed to be used by intensive care units, blood is removed from veins in the patient's arm and enters the machine, where magnetic particles are added.

These are designed to seek out and bind to the dangerous bacteria that cause sepsis as well as little floating scraps of endotoxins that causes septic cascade.
Once bonded together, they are caught by a powerful magnet and the 'cleaned' blood is then returned to the body.

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How to treat leukemia effectively

Acute lymphoblastic leukemia is a type of cancer in which the bone marrow produces too many immature white blood cells

Activation of a protein called STAT5 causes competition among others that leads to acute lymphoblastic leukemia ALL.

According to new study, competition among some proteins causes an imbalance that leads to leukemia .

Using a drug that will stop the initial activation of STAT5 and reverse the natural balance of protein will leads to effective treatment of acute lymphoblastic leukemia.

Researchers used innovative methodology by combining mouse models and patience samples in high-throughput DNA sequencing, epigenetic and proteomic analysis and discovered that patients with a high ratio of imbalance proteins of STAT5 to IKAROS or NF-KB had worse prognosis.