Q&A Session – June 2005

Topic: CML and GIST : Everything that you wanted to know

Session: 5th June 2005, Goregaon Sports Club
Panel Discussion during the Friends of Max  All India Patient Meet – Together we Share and Learn

Moderator    Dr. M.B. Agarwal (MBA)
Dr. S.H. Advani (SHA)
Dr. Pankaj Shah(PS)
Dr. Shyam Agarwal (SA)
Dr. Raghunadharao (RR)
Dr. Senthil Rajjappa (SR)
Dr. Ramanan (RA)
Dr. Chirag Desai(CD)
Pat Garcia Gonzalez


1    Round 1
1.1    What is blood cancer, leukemia? Dr. Advani
Our blood is primarily formed within the bone marrow, and all cells such as white cells, red cells, platelets are all made in adequate proportion as per need.
The production of various components of the blood is regulated.
When this regulation (control) of production of WBC (white blood corpuscles) is lost, or goes awry, resulting in an increased production of the WBC cells, the condition is classified as leukemia.
A large part of the new ‘increased’ number of WBC are ‘immature’, not developed enough, and their interaction with RBC (red blood corpuscles) and platelets, result in a drop of their numbers as well.
Any condition, within which the regulated white cells have now a proportion of dis-regulated white cells infesting them, is classified by medicine as leukemia.

1.2    Why does one get leukemia? Dr. Pankaj Shah
For victims of most cancers the reasons for developing it are not easy to investigate, or arrive at.
The reasons for leukemia (similarly) are very difficult to pin point.
Whenever this disease occurs, the behavior of our cells, right from their nucleus changes in a fundamental way.
Glivec is magical because it directly tries to correct the behavior of the cells, unlike all previous forms of cancer treatment.
Its destiny or God’s wish why someone is affected by this disease.

1.3    What is the difference between chronic leukemia and acute leukemia? Dr. Shyam Agarwal

The speed of ‘dis-regulation’ of WBC is what distinguishes between chronic and acute leukemia.
If abnormal cells are doubling at a very fast pace, say in a matter of days, then the symptoms of the patients are quite pronounced, such as new ‘good’ blood is being formed at a slower rate, platelets fall below the requisite…and these happen at a very brisk rate. This is typically classified as ‘acute’ leukemia
If the same abnormal cells, double at a slow pace, say months, then the symptoms can take as long as 6-9 months to manifest themselves. This is ‘chronic’ leukemia
To summarize, this classification depends on the speed of doubling.
Further classification of the disease, is based on whether the affected dis-regulation is part of myeloid (Myeloid Leukemia), or lymphoid (Lymphatic leukemia)
‘Acute’ is typically something that needs more attention, because the speed of symptoms, deterioration and impact are much faster. It should be taken seriously. If not treated, life expectancy falls to less than 4 months.
1.4    I am told that chronic myeloid leukemia has 3 phases. Please explain – Dr. Raghunadharao

CML can typically be classified into three phases:
Chronic Phase – Blood counts go awry (increase) and enlargement of the spleen occurs. Typically a patient experiences increase in size on the left side of his stomach, has difficulty eating, and has a feeling that his stomach is not full post eating. If not treated, this lasts between 18 months to 30 months. Most medicines act immediately on patients in the chronic phase. It is easiest to control the disease at this stage.
Accelerated phase – After some time in chronic phase, the disease progresses into the accelerated phase. The disease stops reacting to medicines, and some months later
Blast Phase – Similar to Acute Phase, the disease develops very fast, lymph nodes appear, and bleeding occurs.

1.5    Can CML be diagnosed by simple blood test? – Dr. Senthil Rajjappa

Simple blood test, Complete Haemogram  (CBC – Complete Blood Count) shall easily indicate CML, typically evidenced by increased WBC, possibly accompanied by elevated hemoglobin or platelet count.
An experienced pathologist can look at the peripheral blood smear and can give an opinion on the disease.
Sometimes the peripheral blood smear (part of CBS) can be mis-leading, because a similar count might result due to other problems also, and hence this finding should be confirmed by further clinical tests (cytogenetic analysis or reverse transcriptase polymerase chain reaction (RT – PCR)

1.6    Please explain about cytogenetic and molecular tests to confirm CML. – Dr. MB Agarwal
Cytogenetic Test – Involves Bone Marrow testing, primarily in which a sample of the bone marrow is ‘cultured’, could take time upto a few weeks. The pattern which is looked out for is a genetic repetition, called the ‘Philadelphia Chromosome’.
 Note: Glivec works only for CML patients who have Philadelphia Chromosome positive.
Molecular Tests – bcr-abl (Fish or PCR are the underlying technologies to conduct the test.). The typical results of this test are presented as ‘% (percentage) of bcr-abl’, and this just re-affirms that the fact that the patient has CML, has a percentage of his cells showing bcr-abl characteristics, and can be treated with Glivec.
If the patient does not have Philadelphia chromosome, does not have bcr-abl, the patient can be suffering from ‘atypical’ CML, or some other form of CML and Glivec cannot be used in these cases.

1.7    What would happen if CML is left untreated? – Dr. Chirag Desai
Even if a patient is not suffering from external symptoms, a patient should still not ignore the disease, because it can have ramifications in the future.
Typically an un-treated patient has a life span of 2-3 years. 10% of un-treated patients reach blast phase within 2 years, and 25% reach the same every year from thereon.
If left un-treated the disease is like a slow poison and shall eventually be fatal.

2    Round 2
2.1    In old days, spleen removal by surgery and radiation to the spleen were used. Discuss. – Dr. Advani
Fifty years ago CML had no known treatment. Till about 40 years ago, there were very few remedies and the focus of the doctors was to make sure that the patient suffers from as less pain as possible, in relation to the disease.
Typical pain areas were spleen enlargement, and blood counts going awry.
Spleen removal or spleen radiation was the common way to reduce the spleen size and the blood counts. This was no cure for the disease, but used to reduce the pain for the patient. Having said that, because this was not a cure, eventually all cases would progress from chronic to accelerated phase to acute turning fatal.
In contrast today, even if your spleen is enlarged, surgery and radiation are not at all used for treatment, because of other viable options.

2.2    When chemotherapy began, drugs like Busulphan (Myeleran) and hydroxyurea (Hydrea) were used. Please discuss advantages and disadvantages. – Dr. Pankaj Shah
In 1953, Busulphan was first created. Initially it was thought to be the magical cure for CML. In retrospect though, it is clear that most medicines which have come out in the past 50 years, have primarily worked at controlling the counts, and reducing the enlargement of the spleen.
None of the earlier medicines work on the Philadelphia Chromosome, which as a cause of CML was identified much later.
Hydrea was launched about 15 years after Busulphan
Busulphan was normally available in dosage of 2mg and administered in dosage of 6-10mg and used to bring counts in control within 2-3 months. Busulphan was efficient in maintaining the patient in chronic phase for 3-4 years, but eventually the patient would graduate to the blastic phase and post which the life expectancy was around 1 year.
Busulphan had side effects like cataract, darkening of skin, pulmonary fibrosis within the lung.
Hydrea in doses of 3-4 mg was efficient in bringing counts in control within 15-20 days. It was very effective in keeping counts and spleen size within control.
Busulphan extended the life span of the patient to 45 months, while Hydrea extended it to 52 months. Hydrea also eventually terminated in blastic phase and then fatality.
Hydrea had its own side effects like intolerance to heat (patients stop perspiring).
Hydrea and Busulphan helped only control the disease for 3-5 years. Also they did not necessarily extend the life span of the patient, what it did was make sure that the 3-5 years the patient had to live post detection was without the painful effects of awry blood counts and enlarged spleen.

2.3    Then came Interferon therapy. Please discuss. – Dr. Shyam Agarwal
Interferon is an injection that controls the Philadelphia Chromosome.
The disease is primarily driven by Philadelphia Chromosome. Both Hydrea and Busulphan don’t control the Philadelphia Chromosome.
Interferon is an injection that had to be had everyday. It had side effects like fever, body ache, altering blood counts.
20-30% patients in whose case, Interferon managed to control the Philadelphia Chromosome, definitely gained in terms of life expectancy and span.
Interferon is still widely used, sometimes in conjunction with Glivec, because it effectively suppresses Philadelphia Chromosome.

2.4    Bone marrow transplant is a cure for CML. Who should undergo this procedure? What is the cost involved? What are the disadvantages? Which are the centers in India transplanting CML? Is there a waiting period? How long the family has to stay in that centre? Dr. Raghunadharao
Bone Marrow Transplant (BMT) primarily involves removing the diseased Bone Marrow (BM) from the patient, and replacing it with a healthy BM.
BMT is not like blood transfusion. Just like blood transfusion can only be done within same blood groups, BMT also has certain restrictions.
BMT requires HLA typing to match. HLA typing match is tried with siblings, since its best to find a related donor. Even twins qualify to donate the marrow, if the HLA typing matches.
BM matching (HLA typing) can also be done with an un-related donor via a BM bank (transplant registry). This kind of a donor is a ‘matched un-related donor.’
BMT can also be done using the patient’s own stem cells.
BMT is most effective, if we can find a related donor whose HLA type matches.
The charges involved in BMT itself are not very high, they are comparable to normal chemotherapy, what is expensive is the post transplant hospitalization costs. A patient undergoing BMT, needs to be in isolation in a clean anti-septic environment, to prevent infection. We need to keep the patient in isolation, till the new transplanted marrow starts producing blood, also, till such a time, the patient needs to be constantly given an infusion of good blood. The ‘new’ blood which shall be generated by the new marrow needs to be accepted within the system, and for this we need to facilitate the patient with medicines and external help.
If BMT goes without complications, in an entry level government hospital, it shall cost around 2.5 lacs. It could vary from 4-8 lacs if done in a private hospital.
Transplant is possible in hospitals in Mumbai, Delhi, Ahmedabad (GCRI), Hyderabad, Chennai, CMC Vellore.
Since a typical transplant center has no more than 2-3 beds, and trained staff is just about adequate the patient is wholly dependent on the trained staff. Typically each patient requires 1-2 months of the facility. If there are more patients than can be accommodated then definitely there shall be more waiting time.
Some other transplants (other diseases like thalassemia) need to have higher priority than CML patients, and hence sometimes the waiting time can increase because of out of queue patients of other diseases.
Average waiting list is around 6-12 months.
The whole transplant cycle takes around 2 months.

2.5    Glivec is a major breakthrough in treatment of CML. Is this true ? – Dr. Senthil Rajjappa
Glivec is definitely a revolutionary breakthrough. It has been rightly called the ‘Orange Magic Bullet’.
Glivec directly targets the bcr-abl protein and degrades it, to prevent progression of the disease.
2.6    Kindly discuss dose, schedule, and duration of therapy and advantages of Glivec therapy. – Dr. MB Agarwal
Standard dose is 400mg. Some of the patients who cannot withstand 400mg are given dosage of 300mg. Taking Glivec less than 300mg is not at all recommended, since it is not effective at all.
The medicine needs to be taken everyday, once a day. Patients on higher dosage like 600 or 800mg might find it convenient to split the dose into two portions.
Duration of therapy is not known at this moment. Looks like it shall be a life long drug, or at least needs to taken for a really long time.
Patients who have stopped taking Glivec for some time have had a relapse in bcr-abl.
Duration of therapy is typically going to very long.

2.7    How do you decide the dose of Glivec ? Can I increase the dose? What are the advantages and disadvantages ? Dr. Chirag Desai
In chemotherapy, the logic is to administer the maximum tolerated dose (MTD) to the patient. The MTD is typically determined during clinical trials and tests.
Chemotherapy works on the principle of destruction of mutant cells.
Glivec is not chemotherapy and does not work with the same philosophy. In administering Glivec, the dosage is decided upon the optimal biological dose (OBD).
Glivec’ s OBD was tested in clinical trials with various dosages. It turned out to be most effective in dosage of 300 mg and above. The optimal dosage for Glivec is around 400mg in which case it degrades bcr-abl quite effectively.
Certain patients cannot withstand 400mg and hence for them the dosage has to be reduced to 300mg. Dosage less than 300mg is an under-dose and should not be administered.
For accelerated phase or blastic crisis the correct dose is around 600mg.
Some patients don’t progress to hematological control or cytogenetic control with the normal dosage, and for such patients the dosage can be increased.
Patients should never increase the dose on their own. They should do it only in consultation with the doctor.
There have been studies done by administering 800mg to patients, the results have been good, but since the number of patients have been quite limited in this sample, the results cannot be generally accepted.
Skin rash, weight increase, nausea, problems with the liver could be some of the side effects associated with an increased dose.

3    Round 3
3.1    Is Glivec therapy indicated for a person having HLA matched sibling donor for transplantation? –Dr. Advani
Every treatment has its advantages and disadvantages.
At this moment about 5-10% of the patients don’t respond to Glivec. It’s possible that moving ahead in the future, quite some more patients stop responding to Glivec. The symptom would be the presence of Philadelphia Chromosome inspite of Glivec administration.
The other disadvantage of Glivec is it needs to be taken life long.
In comparison, transplant is a one time procedure, requires around, 3 months of procedure time and then it is done. Once it is done, most ‘lucky’ patients can live a normal life.
BMT though, can only be done for young patients, who have a perfect donor. Another disadvantage is the fact that BMT can be fatal for about 5-10% of the patients.
Doctors typically discuss all the above issues with the patient before they decide on Glivec or BMT, or a combination of both.
If for example, a patient says that he is not ready to take even a little risk, for him the best thing to do is take Glivec. A patient who can take 5-10% risk can opt for BMT.
Treatment advice is on a case to case basis.
BMT is preferred more at a younger age. Beyond 40, it is more risky. Post BMT, certain complications like ‘graft versus host’ disease can happen. In this the donor’s marrow reacts with the patient’s body, leading to a lot of complications, which might require medical help all through life.
Post BMT, CML can re-occur in about 5-10% cases, but to counter this, the donor’s stem cells (lymphocytes) are administered again to the patient.

3.2    What is meant by standard transplant, mini-transplant and auto-transplant? Dr. Pankaj Shah
In a standard BMT, the existing marrow of the patient is completely ‘burned’ and destroyed, either through radiation or chemotherapy.
The next step is to install the compatible bone marrow from the donor in the empty space of the original marrow.
Patients on Glivec who have not yet received cytogenetic remission even within a year, they should give BMT a serious thought, if they have a compatible donor.
Patients, who after BMT have no ‘graft vs. host’ disease, have the chance of a great life post BMT.
In mini transplant, the whole of the marrow is not burned, and instead part of the marrow is transplanted, and the body of the patient is encouraged in the hope that ‘graft vs. leukemia’ effect takes place; in effect the graft fights the bone marrow. This is less aggressive and risky than the whole marrow transplant.
In auto transplant, patients who have achieved remission (cytogenetic and hematological), their bone marrow samples are collected, cultured (to make sure that the sample contains only clean stem cells) and then the existing bone marrow is burned and replaced with this clean sample. This is Autologous BMT.
Auto Transplant is no longer in fashion (commonly practiced), because the cure rates are very low.
Mini transplant is simpler to do, but is still in experimental stage. A lot of data regarding this practice is still trickling in.

3.3    Is transplant possible, if a person taking Glivec therapy changes his mind after one or two years? Dr. Shyam Agarwal
Transplant is certainly possible for Glivec patients, but data on the efficacy of the same is not easily available since Glivec is quite a recent phenomenon.
Patients who don’t have cytogenetic remission with Glivec are clear candidates for trying to have a BMT.
Patients responding to Glivec, also don’t have a restriction from trying to find a permanent cure using BMT
Patients who have had a cytogenetic remission with Glivec, but later suffered from a relapse should also try for a BMT
4% of the patients who have had a cytogenetic remission suffer from a relapse.
To summarize Glivec is not a hindrance to BMT as such.

3.4    Is transplant possible, if I don’t have a brother or sister? Can I get a donor from the community? Dr. Raghunadharao

There are limited numbers of HLA types within a community just as there are limited number of blood groups (four), but HLA types are not just four, they could a large number around 40.
A community member who has a matching HLA type would be classified as a matched un-related donor.
Some western countries gather information of HLA types as a standard process, and if the owner agrees then this is published in a public list. (HLA typing registry)
Someone who is looking for an un-related donor, can search at HLA typing registry.
The transplant procedures for an un-related matching donor, and a related matching donor are quite different in execution.
India does not have a donor registry and hence finding a non-related matched donor and doing a BMT is very rare.

3.5    I am on Glivec. I want to have a baby. Your suggestions. If husband is on Glivec, can the wife become pregnant ? Any effect on the child ? Dr. Senthil
Avoid becoming pregnant when on the drug.
If you do want to conceive, then stop the drug at least for a period of 1 month, before you try and conceive.
Even if the husband is on Glivec, and the wife wants to have a baby, the would- be dad must stop Glivec a month prior to conception.

3.6    What is the best time of the day for taking Glivec? Can I split up the dose ? What should be the relationship with food ? Dr. M B Agarwal
The best time for the medicine is at night after dinner.
If the dosage is less than 400mg, it’s not recommended to split the dose. If the dosage is higher, a split is possible but not more than 2 parts.
It should preferably always be taken after food.

3.7    After starting Glivec, my weight has increased, my eyes are puffed and my legs are swollen. What should I do ? Is there any way to reduce the weight? Is there any specific diet? Dr. Chirag Desai
Patients who are faced with weight increase and swelling, normally just need to give it time, the symptoms go away on their own.
If some patients face extreme symptoms, then they can take diuretic kind of medicines which are normally taken in the course of blood pressure problems. This should of course be taken in consultation with a doctor.
Salt can be reduced from the diet, if the patient faces persistent swelling or puffing.
Intake of calories can also be reduced.

4    Round 4
4.1    After starting Glivec, I have been getting body pain, backache. It is unbearable. Please advice – Dr. Advani
Some patients shall suffer from side effects. For extreme body ache, we administer standard pain killers, and for most patients, the symptoms stop after that.
For some other patients who have quite a few side effects, we sometimes either stop the medicine intermittently or reduce the dosage.

4.2    After starting Glivec, I have become very fair; however, this fairness is patchy on my face. Please advice. Are there any other complications related to skin? – Dr. Pankaj Shah
For patchy fairness, there are quite a few cosmetic products which shall help.
Avoiding direct contact with sun light is another good strategy to deal with pigmentation side effects.
Some other side effects on the skin like dermatitis, peri-orbital edema, face edema; eyelid edema or itching could also be possible.

4.3    My doctor stopped Glivec as my liver function was affected. Your comments. – Dr. Shyam Agarwal
It is essential to investigate the cause of the problem as either being a simple viral hepatitis or is it because of a side effect of Glivec.
Irrespective of the reason, Glivec must be stopped, especially, if the SGOT, SGPT  parameters are more than 5 times abnormal.
The drug should be stopped until the overall condition of the liver can be brought within control.

4.4    When I am on Glivec, can I take Crocin or Paracetamol for fever?  If no, what should I take for fever? Dr. Raghunadharao
Some medicines definitely affect the efficacy of absorption of Glivec within the blood stream, in some patients.
Paracetamol and Rifampicin, medicines given during Tuberculosis do affect the absorption rates. Normally for most patients, Paracetamol can be taken along with Glivec, but not only should it be informed to your doctor, it should be discussed as well.

4.5    After starting Glivec 400 mg/day, my WBC count is below 2000/cmm. What should I do? Can I reduce the dose? How do you choose between 300 mg/day and 400 mg/day of Glivec? Dr. Senthil
If counts have drastically fallen, it is recommended that you stop the drug for a short period of time (around 2 weeks), re-test, and if counts are ok, then restart the medicine at normal dosage.
If counts again fall below, then stop again, but this time restart with a lower dosage and gradually increase it back to your normal dosage.
You should not take a dose of Glivec less than 300mg.
An Injection called GCSF, Granulocyte Colony Stimulating Factor, available under brand names like Nupogen, can also be used to prop up the WBC counts. This shall facilitate taking of normal dosage of Glivec without WBC count drops.
All of this should be managed by a senior doctor and patient should not decide on his own.

4.6    After starting Glivec 400 mg/day, my platelet count is 35,000/cmm. What should I do? Dr. MB Agarwal

Normal platelets are around 1,50,000. Even if the platelet count falls to around 50,000 most doctors would not like to reduce the dose of Glivec.
Doctors get concerned only if platelets fall below 50,000; its possible dosage is reduced to 300mg, but not less than that.
If platelets fall really low, Glivec would have to be stopped for some time.

4.7    After starting Glivec, my Hb is 6 g/dl. It’s not improving with any tonics or food. What should I do ? Can a person with thalassaemia minor take Glivec ? – Dr. Chirag Desai

If Hemoglobin is low in conjunction with corresponding decrease in platelet and WBC, then the points above explain how to take care of the same.
If only Hemoglobin is low, then check for iron or vitamin deficiency, and correcting these should correct the problem.
If none of the above is solving the problem, do a bone marrow test to verify the status of your disease, whether it is still in chronic phase or has migrated to blastic phase.
If it has progressed to blastic phase, it might be a good idea to increase Glivec dosage.
If it is not in blastic phase, then the fall in hemoglobin is a side effect of Glivec, which has been observed for 1 out of 1000 patients. For such a patient either blood transfusion can be suggested or Erythropoeitin (injection) can be administered.

5    Round 5
5.1    Does Glivec therapy produce calcium deficiency? Does it cause infection especially in the peri-anal region? Do woman get early menopause following Glivec therapy ? Dr. Advani
None of the diseases can directly be attributed to Glivec, though Glivec can cause calcium deficiency in aged patients.
Glivec would not have any correlation with peri-anal infection.
There is no proven association of Glivec with early menopause. It is possible though that menstrual cycle could be affected.

5.2    Despite taking Glivec – 400 mg/day, my WBC count remains around 25,000/cmm, can I increase Glivec dose? Dr. Pankaj Shah
The decision should be taken by a qualified doctor. Doctor can increase dose upto 800mg.

5.3    I am on Glivec 400 mg/day. My platelet count is always around 800,000/cmm. Can I increase Glivec? Dr. Shyam Agarwal
Normally in CML platelets increase but with medicine it comes back to around 1.5L
Dose can be increased by doctor if needed.

5.4    Which cytogenetic and molecular tests should I do while taking Glivec ? How often should they be done ? What information is obtained from these tests?  Dr. Raghunadharao
Tests are done to monitor the progress of the medicine on the patient.
Blood counts and bone marrow stabilize in a period of around 2 months. So tests of both blood counts and bone marrow betray the patient as a normal person. Hence we need to do cytogenetic tests which reveal the presence of Philadelphia Chromosome within the metaphases. This is measured as a percentage. The falling percentages indicate the progress of the medicine. Doctors use this information to decide the dosage and pattern of administration of the medicine.
If on the molecular level, cytogenetics have turned negative, then bcr-abl should be tested for bcr-abl reverse transcript (polymrase chain reaction).
Once you are on medication, the first blood test and marrow test should happen within a month.
Cytogenetic tests are typically repeated between 1-3 months. Some tests can also be done once in 6 months.
If you a chronic case for over 5-6 years, then the doctor might decide to test you once in 6 months or in very safe cases, once a year.

5.5    What is meant by Glivec resistance or refractoriness?  Dr. Senthil
Refractoriness means that the drug is not having the desired effect on the patient.
Can be figured from any of the standard tests which are performed on the patient.
If within 3 months of starting Glivec, the blood counts don’t stabilize, it classifies as a case of hematological resistance.
If at the end of 6 months, if there is absolutely no cytogenetic response, or if, If at the end of one year, if the Philadelphia Chromosome does not fall by 35%, then it can be classified as hematological resistance.
Resistance means either increased dosage or BMT should be evaluated.

5.6    Can I take higher doses of Glivec ? Can I take other drugs like interferon, cytarabine, Hydrea etc. together with Glivec ? Dr. MB Agarwal
It’s perfectly possible that Glivec can be complemented with other drugs based on the decision by the doctor.

5.7    I understand that there are newer drugs coming up which may be better than Glivec. I have heard about AMN107 and BMS354825. When will these drugs be available and should I change to them ? Dr. Chirag Desai
These two medicines could provide hope for patients who develop resistance to Glivec in the future.
They are in pretty early stage, and trials are going on. Once approved, these medicines could be available for general use.
Time frame 5 to 7 years.


6    Round 6
6.1    My son is 6 years old. His weight is 15 kg. He has CML and doctor wants to put him on 400 mg of Glivec. Is  he right ? Dr. Advani
Glivec is given to children in lower dosage. If a child is above 30kgs he is given 400mg. If a child is less than that, we give him either a dose of 200 or 300mg.

6.2    Can Glivec cure CML? What has been the longest duration of Glivec therapy? Dr. Pankaj Shah
Glivec was introduced in 1998. Longest follow-up commonly found is around 5 years.
If the drug is stopped, the disease relapses, so at this moment patients have to continue having it.

6.3    Is there a role of wheat grass juice with Glivec? Dr. Shyam Agarwal
There is no such established co-relation, but the patient can definitely have harmless supplements.

6.4    My doctor has asked me not to get married. Is it right? Can I have normal sexual life? Can I join a gym? Dr. Raghunadharao
There is no such restriction, either scientifically or medically.
Normal sexual life can be practiced. It’s important to remember to use contraception, and in case a conception is planned then the medicines should be stopped at least 1 month prior to it.
Patients can definitely join a gym and work normally.

6.5    Can I work as before, while taking Glivec ? Dr. Senthil
You can work normally as before.

6.6    Is this disease contagious? Is this disease hereditary? Dr. MB Agarwal
No, CML is not contagious nor is it hereditary.

6.7    I am depressed and I just cannot cope with this diagnosis. Can I be helped ? Dr. Chirag Desai
The patient must seek help from the doctor, family, support structure of Max Foundation, cancer support groups, other patients, and last but not the least, a qualified psychiatrist.

7    Round 7
7.1    Are there other blood cancers where Glivec is useful? Dr. Advani
Glivec is used in other cancers which have Philadelphia Chromosome (Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia )

7.2    What is GIST ? Dr. Pankaj Shah
First seen in 1983
Initially called as intestinal sarcoma
GIST is Gastro Intestinal Stromal Tumor

7.3    How is it diagnosed ? Dr. Shyam Agarwal

GIST is a tumor in the stomach or intestine.
Causes bleeding or other blockages
This sort of cancer can flow into the liver and affect the functioning of the same.
Diagnosed either through operation or biopsy (tissue diagnosis), to investigate presence of C KIT or CD117, involves a process of staining the cancer cells.

7.4    How common is GIST ? Dr. Raghunadharao
Every year throughout the world there are around 3000-6000 patients
Probability is lower than CML
Only 3-6% intestinal tumors are GIST

7.5    I have GIST. How long I have to take Glivec? What is my prognosis? Is there any alternative treatment for GIST? Dr. Senthil
Need to take Glivec, as long as it works for you.
Typically the response for Glivec is around 2 years for advanced/metastatic GIST.
Patients who have lesser disease do much better than those who have more.
There is an alternative called Sumitinib (Pfizer), which is very similar to Imantinib.
Chemotherapy was used earlier, but is not recommended at all for GIST

7.6    Are there any other cancers where Glivec works? Dr. Chirag Desai
Some other forms of  blood cancers
Some forms of skin cancers
Bone Cancers like sarcoma (Dermato Fibro Sarcoma)

8    Questions for TMF
8.1    How many patients in India are getting Glivec?
3600 patients
( Note : Since this meeting the number has increased to more than 4000)

8.2    I had applied for Glivec but I was denied. What is the policy ?
Patient has to be Philadelphia Chromosome positive CML or C KIT positive GIST
Patient should not have access to reimbursements, and not be able to afford medicines on his own.
No limitation to the number of patients within GIPAP

8.3    Will I get Glivec through GIPAP programme lifelong?
Novartis has promised GIPAP shall be on, as long as it necessary


9    Open Questions
9.1    My tooth has to be removed, can I remove it.
If the blood counts are ok, the tooth can be removed.
No need to wait till remission is achieved.

9.2    I have been on Glivec for 2 months with different dosages (high to low). I have ulcers in the mouth. Is it related?
If the dosage has been reduced because of low counts, then it is very much possible that the low counts are causing the oral ulcer.
Otherwise, oral ulcers are not related to Glivec.

9.3    What it the cost of the test for molecular response?
Varies between 2000 to 8000 INR

9.4    Do I have to keep getting bone marrow tests done?
Cytogenetic tests (1 in 100 cells) are high level tests and only indicate crudely the response of the patient to the drug.
Molecular tests (1 in 10,00,000 cells) are more accurate
These tests need to be done regularly to monitor the progress (improvement) of the disease

9.5    Blood stain vomit, is that related to Glivec
There is no correlation, though it could be because of very low platelet count.

9.6    Can I smoke, have tobacco, or alcohol while on Glivec?
Medically none of the above are recommended
Glivec though does not interact with any of them directly

9.7    We already have a child. Does my taking Glivec now affect him?
If the child is normal, then there is no reason to believe he has CML
A routine blood test would confirm the same.

9.8    Does Glivec cause low sperm count?
No such correlation has been proven in humans. Though 40% drop in test rats has been seen.

9.9    Even with molecular remission, I have been advised to continue with Glivec. Why?
Stopping the medicine in the past has caused relapse in almost all cases.
At this moment it looks like Glivec is a life long dependency.

9.10    Can I supplement with Ayurvedic medicines?
There is no known Ayurvedic medicine which cures CML.
Harmless supplements like vitamins can be taken.
Be careful of metal content within Ayurvedic medicines, which may harm liver, marrow or kidney.

9.11    Interaction with grape juice?
Interaction with ‘grape juice’ is not Indian ‘grapes’, but with grapefruit juice, it looks like a sweet lime, but the juice is bitter
Should not be had within an hour of medicines (in either direction, before or after), because it affects absorption of Glivec within blood.

9.12    Can I take other drugs as per requirement, with Glivec?
A local doctor would be able to comment on the same.

9.13    Is there a diet which helps CML from occurring?
Since CML has no known causes, there is no diet or habit, which helps avoid CML

9.14    Is Glivec nephrotoxic? Will it harm kidney.

9.15    When will I develop accelerated CML?
70% patients in 5-7 years shall achieve complete remission, and hence have no traces of CML.
We don’t know how to predict accelerated phase, because there is no data on the same.

9.16    I have GIST, am on Glivec, can I undergo surgery for GIST
Patients, who have an option of surgery for GIST, must go through the same.
Glivec is only a secondary option for patients who have advanced metastatic GIST (or if disease has spread to other organs) and cannot undergo surgery.

9.17    Would Glivec affect the rest of my body, since I might have to take it life long?
Glivec does not interact with normal body cells; it only fights the CML positive cells.
9.18    When should I tell my child, if he has CML?
The child must be told at some time, it’s the decision of the parents of how to choose the right time. It’s a personal decision of the family.

10    Disclaimer
This session was part of a patient support group meet, organized by Friends of Max on June 5th, 2005 at Goregaon Sports Club, Mumbai.
The aim of this information dissemination is to make patients and their friends, family more technically aware of the nature of their disease. It is structured to be a layman’s guide to the diseases (CML and GIST) rather than a doctor’s manual.
The topics covered here include diverse subjects related to the diseases CML and GIST. Due to paucity of time, and the general nature of the conversation, most the discussions were cursory in nature, and should not be used to derive direction for problems faced by patients. We strongly recommend that patients speak to their respective doctors before taking any decision or modifying their regimen related to their disease.
The views expressed here are just pointed answers to questions from patients and do not represent the opinions of the doctors, Novartis or Max Foundation in total. This is a recording/documentation of an Open House discussion between doctors and their patients. These are not the opinions of Novartis or The Max Foundation.

11    Acknowledgements
This labor would not have been possible without the time, intent and contribution of all the doctors mentioned at the beginning of this document.
A special thanks to Dr. M B Agarwal who orchestrated the whole panel discussion, right from planning/inception stage to moderating and hosting it on stage.
The Max Foundation for its support in many ways and at all times and for providing a common platform for the patients, family and doctors to interact.
To the Max India team for orchestrating and managing the whole exercise
Novartis India for being very supportive throughout this whole exercise.
Last but not the least, a toast to the enormous enthusiasm of each and every patient, their family, Friends of Max volunteers and hundreds of others within the ecosystem who contributed unknowingly to give life to this cause. God bless them all…..