Some Hematology Basics

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huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:19 pm

Well here we are, in the so-called data desert and discussing hematology basics is one way to pass the time. Like many here, I’ve had to do a lot of reading and rereading to understand some of the basics in the Imetelstat space. Hopefully what follows can be of help to those just starting to learn about and understand the hematological building blocks/components of hematology.

Hematology: The diagnosis, treatment, and prevention of diseases of the blood and bone marrow as well as of the immunologic, hemostatic (blood clotting) and vascular systems. Because of the nature of blood, the science of hematology profoundly affects the understanding of many diseases.

I know many of us have spent time reading and trying to understand the biology and science of blood and the myriad of disorders and diseases. So you may not want to review or due to your background need this information. And truthfully, a lot of this is pretty basic for those of us who have been around ImetelChat for a while. At a minimum, I hope you will at least take a look at Part V: Complete Blood Count (CBC), as I think it reflects on how this relates directly to our own personal health care and also check out the post after Part VI on Blood Tests and Bone Marrow Biopsies.

I started on this because I was interested in trying to understand the basics. However blood has seemingly an infinite amount of basics and takes a fair amount of time to make that effort. Google was/is, of course, a key in this process. Most of what follows was me pulling from lots of links provided via Google and pasting in various files for my personal reference. Specifically, what follows are 6 parts of the info gathered.
Part I: Blood cell disorders/diseases
Part II: Some basic blood information
Part III: Blood supply / requirements / transfusions
Part IV: Who needs a blood transfusion and what are the risks?
Part V: Complete Blood Count (CBC)
Part VI: Clinical Trials (MF / MDS)

Part I: Blood cell disorders/diseases:

A blood cell disorder is a condition in which there's a problem with your red blood cells, white blood cells, or the smaller circulating cells called platelets, which are critical for clot formation. All three cell types form in the bone marrow.

Common blood disorders include anemia, bleeding disorders such as hemophilia, blood clots, and blood cancers such as leukemia, lymphoma, and myeloma. Anemias are the most common, where there are not enough red blood cells or the cells do not work correctly, are among the most common blood disorders. According to the American Society of Hematology, anemia affects more than 3 million Americans.

There are many different blood diseases that are diagnosed and treated by hematologists. Some of these are benign (non-cancerous) and others are types of blood cancer. They can involve one or more of the three main types of blood cells (red blood cells, white blood cells, and platelets).

Symptoms of Blood Disorders
• Decreased red blood cells and hemoglobin can cause symptoms of anemia, such as fatigue, weakness, and shortness of breath.
• Decreased white blood cells or immune system proteins can cause recurrent fever and infections.
• Decreased platelets or blood clotting factors can cause abnormal bleeding and bruising.

Blood cancers are a group of cancers and you can do a quick read here:
https://www.nhoh.com/types-blood-diseases

You might also review the latest Geron presentation’s summary on pages 8-10 and all the presentation for that matter:
s24.q4cdn.com/668523011/files/doc_presentations/2021/06/Geron-Corp-Deck-May-2021-FINAL.pdf

Blood cancers include leukemia (abnormal stem cells and/or abnormal white blood cells), myelodysplastic syndromes (abnormal stem cells leading to fewer and abnormal blood cells), and myeloproliferative neoplasms (abnormal stem cells leading to more blood cells than normal). One of the myeloproliferative neoplasms is myelofibrosis (MF).

I know we all understand that myelofibrosis is a serious, rare bone marrow cancer that disrupts production of blood cells by extensive scarring in the bone marrow. When the scarring forms, the scar tissue “may” replace bone marrow. With less bone marrow, the number of blood cells “may” drop. As a result, other organs such as the spleen and liver “may” begin to make blood cells to try to compensate, and as a result, grow larger in size. These organs may also enlarge because they trap abnormal blood cells.

huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Re: Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:24 pm

Part II: Some basic blood information:

I found this part as a refresher yet interesting. If you took all the blood vessels out of an average child and laid them out in one line, the line would stretch over 60,000 miles. An adult's would be closer to 100,000 miles long. There are three kinds of blood vessels: arteries, veins, and capillaries. The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood. The veins are thinner walled as the pressure and rate of flow are much lower. The largest artery is the aorta, the main high-pressure pipeline connected to the heart's left ventricle. The aorta branches into a network of smaller arteries that extend throughout the body. The arteries' smaller branches are called arterioles and capillaries.

As we know, blood pressure is highest when our heart beats, pumping the blood. This is called systolic pressure. When your heart is at rest, between beats, your blood pressure falls. This is called diastolic pressure. A hypertensive crisis is a severe increase in blood pressure that can lead to a stroke. Extremely high blood pressure — a top number (systolic pressure) of 180 millimeters of mercury (mm Hg) or higher or a bottom number (diastolic pressure) of 120 mm Hg or higher — can damage blood vessels.

Now give a tennis ball a good, hard squeeze. You're using about the same amount of force your heart uses to pump blood out to the body. Even at rest, the muscles of the heart work hard—twice as hard as the leg muscles of a person sprinting.

The aorta, the largest artery in the body, is almost the diameter of a garden hose. Capillaries, on the other hand, are so small that it takes ten of them to equal the thickness of a human hair. lub-DUB, lub-DUB, lub-DUB. Sound familiar? If you listen to your heart beat, you'll hear two sounds. These "lub" and "DUB" sounds are made by the heart valves as they open and close.
To see the valves in action go here:

www.pbs.org/wgbh/nova/heart/heartmap.html

The movement of the blood through the heart and around the body is amazingly fast and your heart is really good at it — it takes less than 60 seconds to pump blood to every cell in your body. Scientists have estimated that it takes about 30 seconds for a given portion of the blood to complete the entire cycle: from lungs to heart to body, back to the heart and out to the lungs.

It beats about 100,000 times a day, more than 30 million times per year, and about 2.5 billion times in a 70-year lifetime. Each one of us is born with a lifetime supply of 2.5 billion heartbeats. That's right, we're all "heartbeat billionaires." The more we measure wealth by investing our heartbeats in ourselves — and in each other — the happier and healthier we are. Remember, sitting down, drinking water, and taking slow, deep breaths can generally lower your heart rate and btw also helps us to think with more clarity.

Monounsaturated and polyunsaturated fats in fish, nuts, and certain oils (olive, canola, flaxseed) can improve the health of your heart and blood vessels. Stay active. Exercise at a moderate pace (such as by taking a brisk walk or bike ride) for at least 150 minutes a week—or for even longer if you need to lose weight. Heart-pumping aerobic exercise is the kind that doctors have in mind when they recommend at least 150 minutes per week of moderate activity. Fruits: Raisins, prunes, dried figs, apricots, apples, grapes and watermelons not only get the red blood cells flowing but also improve the blood count. Citrus fruits like oranges, amla or Indian gooseberry, lime and grapefruit help to attract iron. They play a very important role in increasing blood count.

Your body will replace the blood volume (plasma) within 48 hours. It will take four to eight weeks for your body to completely replace the red blood cells if you donated. The average adult has eight to 12 pints (6 quarts) or about 5.6 liters of blood, or about as much oil as in a typical car. This 5.6 liters of blood circulates through the body three times every minute. In one day, the blood travels a total of 19,000 km (12,000 miles)—or four times the distance across the US from coast to coast. Blood travels at three feet per second when it leaves the heart, but it slows down as it gets into smaller arteries and capillaries.

https://www.visiblebody.com/learn/circu ... -the-blood

Functions of the Blood: 8 Facts about Blood
• Blood Is Fluid Connective Tissue. ...
• Blood Provides the Body's Cells with Oxygen and Removes Carbon Dioxide. ...
• Blood Transports Nutrients and Hormones. ...
• Blood Regulates Body Temperature. ...
• Platelets Clot Blood at Sites of Injury. ...
• Blood Brings Waste Products to the Kidneys and Liver.
• Red Blood Cells Are the Most Numerous Living Cells in Blood
o Blood is 55% plasma and 45% formed elements.
o Red blood cells, also called erythrocytes, make up most of that 45%. Their primary function is to transport oxygen from the lungs to the cells of the body.
o Red blood cells are disc-shaped. They are flexible and bioconcave—flat and round with depressed centers.
• White Blood Cells Protect the Body from Pathogens
• White blood cells, also called leukocytes, are the disease-fighting components of blood. They account for just 1% of circulating blood but multiply during infection or inflammation.
• There are five types of white blood cells: neutrophils, eosinophils, basophils, lymphocytes, and monocytes. Neutrophils are the most abundant, comprising 60% to 70% of all white blood cells.

huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Re: Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:28 pm

Part III: Blood supply / requirements / transfusions:

Blood supply and requirements in the US:

https://www.redcrossblood.org/donate-bl ... upply.html

The Red Cross provides about 40% of our nation’s blood and blood components, all from generous volunteer donors. But supply can’t always meet demand because only about 3% of age-eligible people donate blood yearly. Each new donor helps us meet patient needs.

Each year, an estimated 6.8 million people in the U.S. donate blood, 13.6 million units of whole blood and red blood cells are collected in the U.S. in a year. Only about 3% of age-eligible people donate blood yearly. Red blood cells must be used within 42 days (or less). Platelets must be used within just 5 days.

Every two seconds someone in the U.S. needs blood and or platelets. Approximately 36K RBC, 10K plasma and 7K platelet units are needed per day. It is essential for surgeries, cancer treatment, chronic illnesses, and traumatic injuries. Whether a patient receives whole blood, red cells, platelets or plasma, this lifesaving care starts with one person making a generous donation.

Hopefully kmall or biopearl123 will chime in here with their research regarding the number of transfusions required by MDS and / or MF patients in the USA and other countries and the potential impact to those numbers by Imetelstat when it is commercialized. In my mind I believe it has to be a significant plus for Imetelstat to reduce the MF/MDS transfusions by hundreds of thousands, possibly millions per year. This is particularly important today as we are in a blood supply crisis.

Blood transfusions:

https://www.cancer.org/treatment/treatm ... sions.html

Whole blood may be called a unit or pint of blood, and equals about 450 milliliters or 16.7 ounces. But whole blood is rarely given as a transfusion. Blood has many parts (called components), and each one does a different job. Whole blood is usually separated into red blood cells, platelets, and plasma. Plasma can be further separated into clotting factors and certain proteins. This lets doctors give patients only what they need. It also helps to get the most out of the donated blood.

When you have a blood transfusion, it’s important to be given the right blood. Blood comes in 4 main types: A, B, AB, and O. These types refer to molecules called antigens on the surfaces of blood cells. Antigens are substances that can cause a person’s immune system to react.

Rh factor is another type of antigen. Blood is either Rh positive or Rh negative. Each person’s blood is one of 8 specific types: A+, A−, B+, B−, AB+, AB−, O+, and O−.
If a person gets the wrong type of blood, his or her immune system will react to it. This is a serious condition that can cause severe symptoms such as fever, muscles aches, and trouble breathing. It can sometimes be fatal.

People with O− blood don't have A, B, or Rh molecules on their blood cells. These people can donate blood to anyone and are known as universal donors.

People who are AB+ have all 3 molecules (A, B, and Rh) on their blood cells and can safely receive blood from anyone.

Other blood types can donate and give to only their matching blood types.

Note: The normal daily production of red blood cells (RBC) in a healthy adult is about 0.25 mL/kg and the average lifespan of the cells is about 120 days, whereas that of transfused RBCs is about 50–60 days and can be significantly shorter in the presence of factors reducing their survival.

huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Re: Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:32 pm

Part IV: Who needs a blood transfusion and what are the risks?

You may need a blood transfusion if you have anemia, sickle cell disease, a bleeding disorder such as hemophilia, cancer or severe injury. For people in critical condition, blood transfusions can be lifesaving. Four types of blood products may be given through blood transfusions: whole blood, red blood cells, platelets, and plasma.

A low hemoglobin count is generally the key indicator and is defined as less than 13.5 grams of hemoglobin per deciliter (135 grams per liter) of blood for men and less than 12 grams per deciliter (120 grams per liter) for women. However, a normal hemoglobin level is 11 to 18 grams per deciliter (g/dL), depending on your age, gender and size. But 7 to 8 g/dL may be a minimally safe level. Often, one unit of blood is enough. In patients who are not critically ill, most studies have demonstrated that a substantially lower hemoglobin level (7 g/dl) can be tolerated if normovolemia is maintained.

Diseases and conditions that cause your body to produce fewer healthy red blood cells than normal include: aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), blood cancers (e.g. MF, MDS, various other leukemias), other cancers, hemolytic anemia, sickle cell disease, severe thalassemia, malarial anemia, fanconi anemia, etc., etc., etc., also certain medications, such as antiretroviral drugs for HIV infection and chemotherapy drugs for cancer and other conditions.

Some doctors believe that hospital patients who fall below 10 g/dL should get a blood transfusion. But research found that:
 Many patients with levels between 7 and 10 g/dL may not need a blood transfusion.
 One unit of blood is usually as good as two, and it may even be safer.
 Some patients in intensive care may do better when they receive less blood.
 Electrocardiographic changes associated with tissue hypoxia can occur at a hemoglobin level <5 g/dL in healthy adults. Studies show mortality and morbidity increase rapidly at levels <5.0 to 6.0 g/dL.
 Individuals with a Hb level of 2.0 g/dL or less had on median 1.0 (interquartile range, 0.5-1.5) day from their lowest Hb to death while individuals with their lowest Hb ranging between 4.1 and 5.0 g/dL had on median 11 (interquartile range, 1-23) days from their lowest Hb to death.

Blood transfusions are generally considered safe, but there is some risk of complications. Mild complications and severe ones can occur during the transfusion or several days or more after.

Clinical research has identified blood transfusion as an independent risk factor for immediate and long-term adverse outcomes, including an increased risk of death, myocardial infarction, stroke, renal failure, infection and malignancy.

All procedures have some risks. The risks of blood transfusions include:

• An allergic reaction. This can be mild or severe. Mild symptoms can include itching, rash, back pain or chills. Severe symptoms can include trouble breathing, chest pain, or nausea. These symptoms may start soon after your blood transfusion or within the next 24 hours.
• Often develop antibodies to transfused red blood cells making it more difficult to find a match if future transfusions are needed. Transfused blood also has a suppressive effect on the immune system, which increases the risk of infections, including pneumonia and sepsis.
• Fever. This can happen within a day of the blood transfusion. It’s usually temporary.
• Destruction of red blood cells by the body (hemolytic reaction). A hemolytic reaction happens when your body attacks the donated RBCs. This happens if you get a blood type that your blood isn’t compatible with. Donated blood goes through a very careful matching process, so this reaction is very rare. If it does happen, it can cause chills, fever, kidney damage, and other serious symptoms. Symptoms can happen during the blood transfusion or in the next several hours. A delayed hemolytic reaction can also happen. This can happen even if you got the right blood type. This may take days or weeks to happen. It may not cause any symptoms, but it can cause your RBC count to be lower.
• Too much blood in the body (transfusion overload). Transfusion overload may happen if a person gets more blood than needed. Cardiac overload—severe shortness of breath from overloading the heart with fluid and other symptoms or lung injury. The symptoms usually happen within a few hours to a day. It’s more common in people with heart problems. Taking diuretic medicine after a blood transfusion may prevent this problem.
• Too much iron in the body (iron overload). This can happen in people who need to have many blood transfusions over time for an ongoing medical condition.
• Viruses being transmitted. The viruses can include HIV or hepatitis. Blood goes through a very careful screening before blood transfusions. The risk of a virus being passed on is very low.
• Graft-versus-host disease. This is a condition where the new, donated blood cells attack cells in the body. It’s a serious but rare condition. Symptoms such as fever and rash may start within a month of the blood transfusion.

Your own risks may vary according to your general health, the type of blood transfusion, and whether you’ve had a blood transfusion before.

In many cases, a person will feel positive effects of a blood transfusion immediately. A blood transfusion typically takes 1-4 hours and generally two hours, depending on the reason for the procedure. The benefits of a transfusion may last for up to 2 weeks but vary depending on circumstances. Recovery time may depend on the reason for the blood transfusion. However, a person can be discharged less than 24 hours after the procedure. Minimally, a person may feel an ache in the hand or arm after a transfusion. There may also be some bruising at the site.

huntingonthebluffs
Posts: 246
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Re: Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:37 pm

Part V: Complete Blood Count (CBC)

NOW, I’m going to chime in here!! If you get annual checkups and have never gotten a complete blood count (CBC), please ask for one on your next checkup or just your next doctor’s appointment and take the time to study the results yourself. Also, ask them to include identification of your blood type. The following definitions will help explain the CBC results. I personally have found things here that doctors have missed, usually borderline but given what I know about me personally and other family members and friends, it has made a “difference” on a few occasions. In addition, it will help you understand more of what is discussed on this and other sites about blood disorders/diseases. Consider it “due diligence” if you are invested in Geron stock 😊.

A complete blood count (CBC) helps your doctor check any symptoms that you may have, such as weakness, fatigue, or bruising. A CBC also helps diagnose conditions, such as anemia, infection, and many other disorders. Usually a CBC includes checking RBC, WBC and platelets of which we all have at least a general understanding.

The hemoglobin (Hgb) test measures how much hemoglobin your red blood cells contain. Hgb is a protein produced by your bone marrow that's stored in red blood cells. It helps red blood cells transport oxygen from your lungs to your body through your arteries. If a hemoglobin test reveals that your hemoglobin level is lower than normal, it means you have a low red blood cell count (anemia).

The hematocrit (hct) is a measurement of how much of someone's blood is made up of red blood cells. The test measures by volume but is then expressed as a percentage. If a person has a hematocrit of 40%, this means that he or she has 40 milliliters of red blood cells in 100 milliliters of blood.

Normal hematocrit levels vary based on age, gender and race . In adults, normal levels for men range from 41%-50%. For women, the normal range is slightly lower: 36%-44%. A hematocrit level below the normal range, meaning the person has too few red blood cells, is called anemia.

There are several reasons why your hemoglobin could be low. Your body may be producing fewer red blood cells than needed. Your body could also be destroying more red blood cells than can be produced. Or you may have experienced a loss of blood.

Low RBC counts, hemoglobin and hematocrit levels can be caused by other things too, such as a lot of bleeding or malnutrition (not enough nutrients in the food eaten). Kidney disease, liver disease (cirrhosis), cancer, and medications used to treat cancer can also cause low levels.

What can I do to increase my low hematocrit? Increasing the consumption of red meat (liver in particular), fish and shellfish (oysters, clams, shrimp, and scallops), dried fruit (apricots, prunes, and peaches), green leafy vegetables, beans, iron fortified breads and cereals, all rich in iron, may help.

The RDW blood test is often part of a complete blood count (CBC), a test that measures many different components of your blood, including red cells. The RDW test is commonly used to diagnose anemia, a condition in which your red blood cells can't carry enough oxygen to the rest of your body.

A red cell distribution width (RDW) test is a measurement of the range in the volume and size of your red blood cells (erythrocytes). Red blood cells move oxygen from your lungs to every cell in your body. Your cells need oxygen to grow, reproduce, and stay healthy. If your red blood cells are larger than normal, it could indicate a medical problem.

A normal nucleated RBC reference range for adults and children is a count of 0 nucleated RBC/100 WBC. Having a count of nucleated RBC is a condition called normoblastemia. Even a count as low as 1/100 is abnormal and should be investigated. Nucleated RBCs (NRBC, normoblasts): an immature form of RBCs seen when there is increased demand for RBCs to be released by the bone marrow, or when there is marrow involvement by fibrosis or tumor; may be seen in severe anemia, myelofibrosis, thalassemia, miliary tuberculosis, cancers that involve the bone marrow, RBC production outside of the bone marrow, spleen disfunction and low oxygen level.

A mean platelet volume (MPV) test measures the average size of your platelets. It’s closely related to a platelet count test, which measures the number of platelets in your blood.

A high MPV means that your platelets are larger than average. This is sometimes a sign that you're producing too many platelets. Platelets are produced in the bone marrow and released into the bloodstream. Larger platelets are usually young and more recently released from the bone marrow. A low MPV is linked to inflammatory bowel disease, chemotherapy and certain types of anemia.

A CBC helps your doctor check any symptoms that you may have, such as weakness, fatigue, or bruising. A CBC also helps him or her diagnose conditions, such as anemia, infection, and many other disorders. A CBC test usually includes: White blood cell (WBC, leukocyte) count.WBCs fight infection. The body makes different types of white blood cells (granulocytes which have granules which secrete important substances), which are vital components of the immune system. Immature granulocytes are white blood cells that have not fully developed before being released from the bone marrow into the blood. They may include metamyelocytes, myelocytes, and promyelocytes. Healthy individuals do not have immature granulocytes present in their peripheral blood. Therefore, the incidence of IGs in the peripheral blood is indicative of substantially increased bone marrow activation, as in different types of inflammation.

The most important infection-fighting WBC is the neutrophil (NEW-truh-fil). The number doctors look at is called your absolute neutrophil count (ANC). A healthy person has an ANC between 2,500 and 6,000. The ANC is found by multiplying the WBC count by the percent of neutrophils in the blood.

Lymphocytes are a type of white blood cell. They play an important role in your immune system, helping your body fight off infection. Many underlying medical conditions can cause lymphocytosis. High lymphocyte blood levels indicate your body is dealing with an infection or other inflammatory condition. Most often, a temporarily high lymphocyte count is a normal effect of your body's immune system working. Sometimes, lymphocyte levels are elevated because of a serious condition, like leukemia.

The Mono test is normally used to help determine whether a person with symptoms has infectious mononucleosis (mono). The test is used to detect proteins in the blood called heterophile antibodies that are produced by the immune system in response to an Epstein-Barr virus (EBV) infection, the most common cause of mono. The most common sign of chronic myelomonocytic leukemia (CMML) is having too many monocytes (seen on a blood test). Having too many monocytes also causes many of the symptoms of CMML. It is often a marker of chronic inflammation, either as a result of infection, autoimmune disease, blood born malignancy or possibly even a lipid storage disease.

Eosinophils; Absolute eosinophil count. An absolute eosinophil count is a blood test that measures the number of one type of white blood cells called eosinophils. Eosinophils become active when you have certain allergic diseases, infections, and other medical conditions.

If basophil levels are low, this may be a sign of an allergic reaction or another condition. High basophil levels may indicate an autoimmune condition or one of several types of blood disorder.

huntingonthebluffs
Posts: 246
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Re: Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:40 pm

Part VI: Clinical Trials (MF / MDS):

I think we all have a little time here to do some due diligence regarding the various drugs in CTs that may help patients with these diseases and why, help us better understand the enormity of the competitive landscape and learn more about the challenges for a pre-commercial biotech getting a drug approved.

There are hundreds , actually thousands, of CTs targeting blood cancers including MF and MDS. If you don’t have them handy, you might find the links below to bring up and browse the lists of trials for MF and MDS. While daunting at first glance, taking a look at the drugs used in a specific CT, where it is in the process through 3 CTs and the number of sites involved can all be indications regarding importance and of course competitive potential to Imetelstat.

If you are like many of us non-medical scientific types, each review of each CT drug can send us down a deep badger hole of unlimited dissection of blood or other cell components each with dozens of terms we need to browse Google for explanation only to find the unending stretch of new terms exhausts and frustrates us to no end along with a jumbled brain. And then when you look at the blood diseases, all the mutations, their causes, etc. it just compounds my throbbing cerebral cortex. Somewhere in there is/are nuggets of gold most if not all of which I don’t have the knowledge base to assess or value and is better left up to those like biopearl123 and others on this board who could explain for us. I’m not saying this self-education isn’t useful to some degree because it is but the most effective/efficient process and method of retention of facts/terms without the lengthy formal education seems to be above my pay grade even as I think I have approached it in a fairly methodical/organized fashion.

However, if you continue reading the CT descriptions not all is lost. You will find they mostly all have a similar format which can be used to understand the target diseases, sponsor, drugs type/classification used(primary, secondary, combination, alternate), description / type of study in terms of phases, randomized, blinded, arms, primary/secondary measures/outcomes, timelines, eligibility, inclusion/exclusion criteria, recruiting status, contacts, locations, etc. Here I find I can compare the studies to Geron’s studies, especially in terms of size of study, recruiting status, timelines, measures/outcomes, interim/final readouts, etc. Interestingly, many focus on spleen volume reduction as primary outcome in 24 weeks, while secondary outcomes focus on reduction in total symptom score and some level of spleen reduction maintenance. Disease modification is even mentioned in some but very infrequently.

Also, most CTs are not looking for R/R to Rux patients so less competition for Geron on that point. I do think the typical patient would prefer oral drugs and may even consider, if allowed, coming back into a combination trial with oral drugs even if technically R/R to Jakafi by itself. Maybe someone could speak to that consideration. However I believe the investigators continue to be excited about and consider the Imetelstat studies high priority. Last, I do think a consideration here is the significant number of trials and drugs being evaluated which points to intense focus and competition to gain drug approval in this space! Truthfully, I’m not totally understanding why that is the case as it was not like that prior to the JNJ discontinuation.

Anyway, I hope some of you will take the time to study the studies and contribute your thoughts and ideas for the rest of us to benefit from. Thanks in advance to all our member contributors/readers and non-member readers as well for keeping this site on target and inciteful. And it would be great for the next one, two or three biopearl123 like contributors to share their wisdom with us as well.

There are approximately 100 MF CTs currently taking place most include the US but not all.

https://clinicaltrials.gov/ct2/results? ... =a&recrs=b

Some CTs we hear about more frequently and likely represent a higher probability to succeed such as the Constellation Pharmaceuticals Manifest-2 Phase 3 study using CPI-0610(Pelabresib) and Ruxolitinib

https://www.clinicaltrials.gov/ct2/show ... sib&draw=2

or the AbbVie REFINE Phase 2 study using Navitoclax and Ruxolitinib.

https://clinicaltrials.gov/ct2/show/NCT03222609

And there are approximately 400 MDS CTs currently taking place
https://clinicaltrials.gov/ct2/results/ ... 20syndrome

huntingonthebluffs
Posts: 246
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Re: Some Hematology Basics

Post by huntingonthebluffs » Fri Jul 30, 2021 10:43 pm

Lastly, here are a couple things I’ve recently picked up that I think are of interest and probably informative for some of us. First link is an article is by Dr. John Mascarenhas including info on patients that are triple negative:

Understanding Genetic Mutations in Primary Myelofibrosis

When should a primary myelofibrosis patient have genetic testing to determine mutational subgroups? Dr. John Mascarenhas explains the different mutations that can accompany a primary myelofibrosis diagnosis and the distinctions in outcomes for patients who are diagnosed with each type of mutation.

https://patientpower.info/understanding ... -288850744

and secondly this link is an article by Dr. Brady Stein and Dr. Naveen Pemmaraju which talks about the use of complete blood count (CBC) referred in in Part V above and bone marrow biopsies:

Diagnosing MPNs: Blood Tests & Bone Marrow Biopsies

Dr. Brady Stein and Dr. Naveen Pemmaraju discuss how MPNs are diagnosed, the necessary blood tests, including platelet counts, and provide a thorough explanation of a bone marrow biopsy

https://patientpower.info/myeloprolifer ... -288850744

rccola335
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Re: Some Hematology Basics

Post by rccola335 » Tue Aug 10, 2021 1:35 am

an excellent summary - that was a lot of work

biopearl123
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Re: Some Hematology Basics

Post by biopearl123 » Tue Aug 10, 2021 3:58 am

Couldn’t agree more, thank you hunt.

kmall
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Re: Some Hematology Basics

Post by kmall » Tue Aug 10, 2021 6:27 pm

Fantastic post Huntingonthebluffs !! Very informative and broken down so everyone can understand. To answer your question on transfusion savings with Imetelstat..... Andrew-bp had at one point did the math.....off the top of my head I remember it being 408,000 units/yr. From my research I came across patient discrepancies in both MDS and MF patient populations, which were nearly double or more......this is globally mind you. So, in theory that 408k could easily be 800k + now.

In terms of savings...... again off the top of my head, I remember it being $250-500 million /yr. Hope this helps. -Kmall

huntingonthebluffs
Posts: 246
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Re: Some Hematology Basics

Post by huntingonthebluffs » Mon Aug 16, 2021 12:45 am

Thanks all for the nice comments. And I appreciate the follow-up kmall! So I did find biopearl123’s post (Reality check – on July 20, 2018). Those are significant numbers and I assume the FDA or any health regulatory or medical entity would not overlook such critical potential and add their support to accelerating the CT process as these and other benefits add up. Although, not sure why, but I have to say I have never seen anything said or in print highlighting Geron’s blood bank savings contribution.

Of course, I realize we seem to be locked into the current CT schedules and getting to the expected approval/commercial events cannot be expedited. However, awareness of what is being left on the table because of regulatory demands will hopefully help keep the pressure on to fully utilize the fast path designations and avoid delays due to mechanics, data/paperwork “user errors”, CRO and investigator missteps, etc.

biopearl123
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Joined: Fri Jul 20, 2018 5:13 pm

Re: Some Hematology Basics

Post by biopearl123 » Mon Aug 16, 2021 4:46 am

Hunt, I posed this question directly in written form at the shareholders meeting. Unfortunately and for unclear reasons it was ignored. bp

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