MEDICAl BLOGS:GRAFT VERSUS HOST DISEASE (GVHD)

The high dose chemotherapy given for certain types of cancer, is called myeloablative therapy because it kills all the normal bone marrow stem cells in addition to killing the cancer cells.In the Allogenic setting, the bone marrow/stem cells, from HLA matched donor, which has already been collected from the donors marrow/stem cells(collected from the bone marrow/ donor peripheral blood via a cell separator) is then infused into the patient ( recipient) with a view to rescue the patient.

RESCUE:

These donor transfused stem cells then home on to the recepient marrow sites and gradually over a period starting from around 14 days onwards, help in re formation of all the three cell lines( RBC, WBC & platelets) in the recipient.  The time for theprocess of recovery  given is variable, but within 4 weeks post PSCT and longer for the post BMT cases.

WHAT IS GVHD?

GVHD is the phenomenon observed as a complication following an Allogenic Bone Marrow Transplant (BMT)or Peripheral blood Stem Cell Transplant (PSCT).GVHD happens when a type of WBC,called the T cells, present in the donorbone, attacks the recipients body cells. 

WHY DOES GVHD HAPPEN?

We all inherit our HLA from our parents which is unique for each one of us, except in identical twins ( who have the same HLA). That is why blood tests are done prior to transplant for the donor and recipient to see how far the HLA match one another.Post transplant, the patient (recipient) bone marrow starts making new blood cells from the donor stem cells. These new blood cells have the donor's HLA pattern. They recognise the HLA pattern on the host (recipient) body cells as foreign and therefor attack some of them. 

The GVHD may affect different areas of the recipient's body. Most commonly it affects the Skin, Digestive system (including the bowel and stomach) and the Liver. 

TYPES OF GVHD:

GVHD can be grouped according to when it starts after your transplant. 

• Chronic GVHD
• Late acute GVHD and overlap syndrome
• Acute GVDH

Acute GVHD:

Acute GVHD, starts within 100 days of the transplant and can be mild or severe. It starts after the new bone marrow begins to make blood cells,the process called Engraftment which usually happens in about 2 to 3 weeks after transplant. 

Acute GVHD may present as :A rash on the palms, soles, ears or even face of recipient. The rash may be itchy or painful. Acute GVHD may also affect the mouth, gut (digestive system) and liver and lead to nausea, loss of appetite, diarrhea and yellowing of the skin (jaundice).

Chronic GVHD:

Chronic GVHD normally starts more than 100 days after the transplant. It normally follows Acute GVHD, but can happen even by itself and affectsthe skin, mouth, gut, liver, eyes, lungs, vagina and joints. 

•  Skin: rash, discoloration, tightness or changes in texture
• Hair: thinning
•  Nails: changes in texture, brittleness or ridges
•  Eyes: irritation, dryness, blurred vision, a gritty feeling
• Mouth: dryness, sensitivity to foods or toothpaste
• Vagina: dryness, irritation, tightening
• Penis: irritation
• Digestive System: nausea, vomiting, diarrhea, loss of appetite, unexplained weight loss
•  Lungs: chronic cough, wheezing, shortness of breath
• Joints: difficulty fully extending fingers, wrists, elbows, knees or ankles
•  Fatigue
•  Low grade fever

Chronic GVHD may be mild or severe, and for some people can go on for several months or even years.

Late acute GVHD and overlap syndrome:

The National Institutes of Health classification includes late acute GVHD (starting after day 100) and an overlap syndrome with features of both acute and chronic GVHD. They are both more likely to happen after mini transplants (reduced intensity conditioning)

Risk factors for GVHD:

A number of factors can increase your risk of GVHD. These include the following

• Unrelated donor transplants. 
• Mismatched donor transplant.
• Large number of T cells in donor marrow/stem cells
• Age:Older the donor or recipient more chances of developing GVHD.
• Having a donor of a different sex to you: If your donors sex is different, the risk of GVHD is slightly increased. More true if a male is the recipient and female a donor who has had children or been pregnant in the past.
• Testing positive for cytomegalovirus (CMV): An otherwise common harmless virus observed in 60% of general population. But if recipient is CMV negative and Donor CMV positive the risk for GVHD is greater.

Benefits of GVHD:

GVHD can be unpleasant and reduce quality of life and in some cases it can be life threatening.

But mild GVHD can lower the chance of leukaemia or lymphoma coming back (relapse) by the graft versus cancer effect provided by the Donor T cells which kill the remains cancer cells.

Therefore treatments to prevent/reduce GVHD are used very judiciously so that the benefits of GRAFT VERSUS DISEASE EFFECT is not lost.

Thanks for reading and please keep visiting our blog to discover and appreciate more Yoddhas. 
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Author- 

   

Dr. Ganjoo 

Head-Yoddhas Medical Expert Panel

MEDICAL BLOG: Targeted Therapies for Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) cells contain an oncogene, BCR-ABL.

(BCR-ABL is not seen in normal cells).

This gene makes a protein, BCR-ABL, which causes CML cells to grow and reproduce out of control. 

BCR-ABL is a type of protein known as a Tyrosine  Kinase.

Drugs known as Tyrosine Kinase Inhibitors (TKIs) target the BCR-ABL and 

are today the standard treatment for CML (in the chronic phase).

These include:

§  Imatinib (Gleevec)

§  Dasatinib 

§  Nilotinib 

§  Bosutinib

§  Ponatinib 

All of these drugs can have serious interactions with other drugs, over the counter supplements, and even certain foods (such as grapefruit and pomegranate). 

Be sure that your doctor always has an up-to-date list of any medicines you are taking, including over-the-counter medicines, vitamins, and herbal supplements. 

You also need to check with your doctor before starting any new medicine, to be sure it is safe.It is also important to understand that all of the TKIs can harm the fetus if taken during pregnancy.

IMATINIB:

Imatinib (Gleevec) was the first drug that specifically targeted the BCR-ABL tyrosine kinase protein and is known as a first generation tyrosine kinase inhibitor.CML patients respond to treatment with imatinib, and most of these responses seem to last for many years. 
This drug is taken orally with food once a day. It doesn't seem to make the leukemia go away and stay away, so patients need to take it indefinitely (or until it stops working). 

Common side effects:

• diarrhea
• nausea
• muscle pain
• fatigue. 
• itchy skin rashes
• fluid buildup around the eyes, feet, or abdomen.:In rare cases the fluid may collect in the lungs or around the heart, which can cause trouble breathing. If you are taking this drug, tell your doctor right away if you notice sudden weight gain or fluid buildup anywhere in the body or have trouble breathing.
• drop in WBC & platelet counts. 

In some patients, imatinib eventually seems to stop working.

Resistance to imatinib seems to be caused by changes in the genes of the CML cells.

Sometimes this resistance can be overcome by increasing the dose of imatinib, but some patients need to change to a different drug, such as one of the other TKIs.

DASATANIB:

Dasatinib (Sprycel) is a second generation tyrosine that is taken orally(by mouth) once or twice daily.

Dasatinib can be used 

* As the first treatment for CML

* It can be used for patients who can’t take imatinib because of side effects 

* If Imatinib is not working. 

Common side effects:

• fluid buildup
• lowered blood cell counts
• nausea
• diarrhoea
• skin rashes. 
• A serious side effect is pleural effusion) and is more common in patients taking this drug twice a day. 

NILOTINIB:

Nilotinib (Tasigna) is another second generation TKI that targets the BCR-ABL protein. 

* Can be used as a first treatment for CML 

* Patient who can’t take imatinib 

* CML no longer responds to imatinib.

Common side effects:

• fluid buildup
• lowered blood cell counts
• Nausea
• Diarrhoea
• high blood sugar
• pancreatitis (rarely)
• This drug can also affect the rhythm of the heart, causing a condition called prolonged QT syndrome. This is why patients should have an electrocardiogram before starting nilotinib and then again while being treated. 

BOSUTINIB:

Bosutinib (Bosulif®) is another TKI that targets the BCR-ABL protein.

Approved by the US Food and Drug Administration to treat patients after they have been treated with another TKI.

Common side effects:

• diarrhoea
• nausea/vomiting
• abdominal pain
• rash
• fever
• fatigue
• low blood cell counts (including low platelet counts, low red blood cell counts, and low white blood cell counts). 

Less common side effects:

• fluid retention
• liver damage, 
• severe allergic reaction. 

PONATINIB:

Ponatinib (Iclusig®) is a new TKI targeting the BCR-ABL protein.

IT HAS SERIOUS SIDE  EFFECTS 

So only used to treat patients with CML if all of the other TKIs don’t work 

or if their leukemia cells have a certain gene change called the 

T315I mutation. 

This mutation (gene change) occurs in the leukemia cells of some CML 

Common Side effects:

• abdominal pain
• headache
• rash 
• fatigue
• High blood pressure
• Blood clots leading to heart attacks and strokes, or block arteries and veins in the arms and legs. 
• Weaken the heart muscle, leading to a condition known as congestive heart failure
• liver problems, including liver failure
• pancreatitis (inflammation of the pancreas, which can lead to severe belly pain, nausea, and vomiting).

Whats new in CML!

Treatment:

Combining the targeted drugs with other treatments:

Imatinib and other drugs that target the BCR-ABL protein have proven to be very effective, but by themselves these drugs don't help everyone. Studies are now in progress to see if combining these drugs with other treatments, such as chemotherapy, interferon, or cancer vaccines might be better than either one alone.One study showed that giving interferon with imatinib worked better than giving imatinib alone. 

A study going on now is looking at combing interferon with nilotinib.Other studies are looking at combining other drugs, such as cyclosporine or hydroxychloroquine, with a TKI.

New drugs for CML:

Because researchers now know the main cause of CML (the BCR-ABL gene and its protein), they have been able to develop many new drugs that might work against it. 

In some cases, CML cells develop a change in the BCR-ABL oncogene 

known as a T315I mutation which is resistant to many of the current 

targeted therapies (imatinib, dasatinib, and nilotinib)

Ponatinib is the only TKI that can work against T315I mutant cells. 

Other drugs called farnesyl transferase inhibitors, such as 

* lonafarnib

* tipifarnib

CML patients may respond when these drugs are combined with imatinib. These drugs are being studied further.

Other drugs being studied in CML include the histone deacetylase inhibitor 

* Panobinostat 

* Proteasome Inhibitor.... Bortezomib (Velcade).

Cancer vaccines:

Cancer cells are different from normal cells, so it is sometimes possible to get the body's immune system to react against them. One way to do this is to use a cancer vaccine -- a substance injected into the body that boosts the immune system and causes it to attack certain cells. Several vaccines are now being studied for use against CML. For instance, in one small study, a vaccine called CMLVAX100 was given along with imatinib and seemed to increase its effectiveness. Research into this and other vaccines is continuing.

Thanks for reading and please keep visiting our blog to discover and appreciate more Yoddhas. 
Feel free to contact the Yoddhas team at team@yoddhas.com 
Join our free patients group https://www.facebook.com/groups/yoddhathewarrior/

Lastly, Praise the Yoddhas; Support the Yoddhas ; Love the Yoddhas!

Author- 

   

Dr. Ganjoo 

Head-Yoddhas Medical Expert Panel

Do I need a "CANCER INSURANCE" - Find out why

Why you should consider a cancer insurance policy?

"You been diagnosed with cancer."
 Nobody would want this even in their worst dreams. The fact, however, is that today's lifestyle has increased the chances of getting cancer. Worse, there are over a 100 types of cancers and any part of the body can be affected. Further, anyone can fall victim to this deadly disease.

In fact, a recent study conducted in Britain by the British Journal of Cancer finds that the lifetime risk of getting diagnosed with cancer has increased over time - from 38.5% for men born in 1930 to 53.5% for men born in 1960. The study concluded that the lifetime risk of cancer for people born since 1960 is greater than 50 per cent now.

In India alone, about 10 lakh people are diagnosed with cancer every year and another six to seven lakh die of it. By 2035, these numbers may almost double to 17 lakh new patients and 12 lakh deaths per annum, according to a special research paper on cancer in India published in Lancet Oncology journal sometime ago.

Moreover, while the probability of getting cancer has increased substantially, the cost of treatment has also gone up many-fold in recent years. In fact, treatment costs now have the potential to wipe out a common man's entire life saving. Worse, the cost of treating cancer abroad can be several times that incurred in India, according to a Times of India report.

This is the reason why comprehensive medical insurance against cancer has become the need of the hour. Although most health insurance policies available in the market today cover almost all major critical illnesses, including cancer, but these policies generally pay only for inpatient hospitalization and for treatment at hospitals in India. They do not cover the entire cost of treatment. Also, the policy amount may not be enough as the common man generally does not go for a health policy of more than Rs 5 lakh. Such limitations may be overcome by opting for critical illness (CI) insurance which is designed to help cover medical expenses that your normal health insurance will not cover.

How to buy your right insurance policy?

Yoddhas is a Cancer support NGO (Regt with 80G,12A) Not-for-profit support community formed by patients and volunteers. It is India’s First Online Support Network for patients. It was started in 2013 by 28 year old patient, Rahul Yadav fighting Multiple- Myeloma a rare form of blood cancer.

We at Yoddhas are working to find various Cancer related insurances policies so that one can pre-emtively  insure and safeguard from the financial needs of cancer treatment.

While we tried studying various insurance policy, we explored various different policies which are active right now and being availed by the public. We also referred to many online websites like PolicyBazar.com and insurancepandit.com to do our comparative studies.

We compared many available policies in India to find out which ones would be best suited for Cancer related cover. Based on our studies these are the four insurance policies where we got a good feedback from the people and we enquired from other patients and people who have either been using or have knowledge about such policies. 

	ICICI Cancer Care Plus	National Insurance+ CPAA Cancer Insurance Policy	National Insurance+ ICS Cancer Insurance Policy	Religare Health Insurance
Eligibility	For anyone aged between 20 and 60 yrs who is not suffering from pre-existing cancer	For members of Cancer Patients Aid Association who are not suffering from pre-existing cancer	For members of Indian Cancer Society who are not suffering from pre-existing cancer	For anyone aged between 20 and 60 yrs who is not suffering from pre-existing cancer
Entry-Exit Age	20 yrs – 60 yrs (renewable up to 70 yrs)	Not given	Up to 70 yrs	20 yrs – 60 yrs (renewable up to 70 yrs)
Sum Assured	Rs 5,00,000 – 25,00,000	Rs 30,000 – 5,00,000	Rs 50,000 or Rs 2,00,000	Rs 15,00,000 – 50,00,000
Policy Term	10 yrs	1 yr	1 yr	1 yr
Premium	For a typical 10 lakh cover -4,604 to 8,945 (for men) 8,602 to 14,845 (for women)Minimum single premium - 1,200 per annum	2,400 to 8,000	Rs 496 (for 50,000 cover) Rs 1,157 (for 2,00,000 cover)	Rs 6482 to 9982(for men and women)
Waiting Periods	For Early Cancer - 12 months from the risk commencement date For Advanced Cancer - 6 months from the risk commencement date Should be able to survive for 28 days from the date of diagnosis	Should be able to survive for 30 days from the date of diagnosis	Should be able to survive for 30 days from the date of diagnosis	Should be able to survive for 30 days from the date of diagnosis

Conclusion

Firstly its always good to be planned for whatever happens. After studying the given policies and as Yoddhas Research Team our feedback is general we can state that the Indian Cancer Society’s policy is very cheap and easily available. Also the maturity amount is not big enough as we know the cost of cancer treatment is high but still the return is much higher if we compare with the premium paid. So as per our research all people should get insured under this policy.

For some selective people who have higher risk of cancer in their family should go for the higher premium policy because of the cost of the cancer treatment. They should get insured under ICICI Cancer care plus Or Religare Health insurance.

Please Note: This is a basic study based on patients and public feedback and secondary data from the various sources. We are not in any manner promoting any particular thing over another. Please do your research to make an informed decision.

Co-Authored By:

Rohit Banka 

Research and HR Consultant

Rahul Yadav 

Founder- Yoddhas and a Blood Cancer Fighter

Thanks for reading and please keep visiting our blog to discover and appreciate more Yoddhas. Do subscribe 
Feel free to contact the Yoddhas team at team@yoddhas.com 
Join our free patients group https://www.facebook.com/groups/yoddhathewarrior/

Lastly, Praise the Yoddhas; Support the Yoddhas ; Love the Yoddhas!

References:

www.policybazar.com

www.insurancepandit.com

www.indiancancersociety.org

http://www.cpaaindia.org/

https://www.facebook.com/groups/yoddhathewarrior/ (Yoddhas Patient Group)