Vidaza and my MDS/AML Treatment Mystery

[King Farouk]

Hello Everyone,

This is my first time time posting on the site. Our story takes a different turn and still is. My Dad is 78 and was diagnosed in Kuwait initially with AML, RAEB, complex cytogenetics but there was a debate on the number of blast cells counts which placed him at the border of the WHO classifications MDS/AML and due to his age and poor performance status he was not given the best options and there were not any cases treated with Vidaza or Dacogen the drugs were available be procured but the application is non existent. We flew dad to Boston at MGH cancer center, the journey itself was a struggle and dad arrived in Boston a very sick man. We checked in at the hospital and with the prior reports from Kuwait and London, a full check up was initiated and of course a Bone marrow biopsy which revealed MDS, RAEB-2, complex cytogenetics and blasts at 11-15% which solved the mystrey of diagnosis. We opted to start treatment with Vidaza (75 MG given by IV Five Days every 28 days ) in Boston as a result of the survival data are more available than Dacogen. After the second cycle of Vidaza, we went for a Bone Aspiration and biopsy and this was around October of 2009 and it revealed a blast count of 27% and therefore a transformation of AML was confirmed. We opted to stay in Boston and continue treatment with Vidaza and supportive care (red blood cells and platelets)and after the Third cycles the counts started reaching incredible heights and after the fourth cycle a clinical response and transfusion independence was gained. His CBC in August of 2009 was HGB of 8.1, WBC of 2.8 and PLT of 13 and after 4 cycles of Vidaza his HGB was at 11.9, WBC of 6.2 and PLT of 106.

Four months had passed and we decided to return home and continue the treatment in Kuwait, the clinical visits and setups were emulated typically like it was in Boston, a once a week clinical visit and a CBC. The counts started to take a gradual straight line graph decline when you plot them, like for example prior to the first day of the fifth cycle his WBC was 3.5 , HGB 10.7 and PLT 78. The treatment continued and there was no evidence to do otherwise as the counts were still decent. Prior to the sixth cycle the decline manifested mostly on the platelets which declined to PLT 35 and then on the day of the cycle schedule shot up back to PLT 50 therefore the decision remained to continue treatment. The weeks proceeding the day of the seventh cycle showed the major decline where WBC 2.7, HGB 11, PLT 20 which is the border of platelet transfusion. The doctors in Boston and Kuwait both recommended to delay the seventh cycle and perform another bone marrow investigation, this revealed no progression of disease and the aspiration slides had only 4-6 % blast cells and the biopsy revealed 7% blast cells as well as 4 normal cytogenetics. The Kuwaiti doctor saw no evidence of a leukemic bone marrow however it remained hypo cellular and transfusion independence is no longer apparent. Both doctors contemplated the possibility of increased toxicity to the drug and therefore they delayed the 7th cycle by about 8 weeks and reduced the dosage to half. This did not seem to improve the condition and the deterioration in the counts continues until today where the last CBC post one unit of red blood cells and 6 units of platelets transfusion indicated a WBC of 1.4, HGB of 8.5 , PLT of 24 and another bone marrow investigation is scheduled for tomorrow before a decision regarding starting the 8th cycle of Vidaza or ultimately change the course of treatment.

Can anyone give me a clue to what is actually going on, has the Vidaza stopped working? does it work on and off? no evidence of excess Blast cells but does that still means bone marrow failure? I cant seem to get a clear explanation to the situation. It is frustrating as it is.

[rose mcmillin]

I am so saddened to hear of your Dads experiences. This disease is such an unpredictable syndrome. My husband is also Raeb-2 and had to stop Vidaza because of low platelets. He missed 5 weeks and his doctor just started him on it again. I really won't know anything about his counts until Monday, and will share them with you then. I don't know if the Vidaza has helped or hurt him this time. However, please remember that not everyone reacts the same nor follows the same course with mds. Take care, Rose

[King Farouk]

Originally Posted by rose mcmillin

I am so saddened to hear of your Dads experiences. This disease is such an unpredictable syndrome. My husband is also Raeb-2 and had to stop Vidaza because of low platelets. He missed 5 weeks and his doctor just started him on it again. I really won't know anything about his counts until Monday, and will share them with you then. I don't know if the Vidaza has helped or hurt him this time. However, please remember that not everyone reacts the same nor follows the same course with mds. Take care, Rose

Thank you Rose for your kind words and support. The downward cycle of Vidaza is effecting the HGB, WBC and Platelets and in my opinion is marginally worse than we started therefore the demoralizing aspect and the loss of quality of life. I wish to investigate Brigitta's link with the new drug Promacta and also neupogin for the WBC and Neuts. I hope we both can figure something out very soon.

Lets keep each other updated.

[Neil Cuadra]

Since your dad still has low counts it would still be called bone marrow failure. But from your description the Vidaza treatments sound like a success. That's a huge drop from 27% blasts last October to 4% to 7% now.

It common with Vidaza that counts may get worse temporarily and that the interval between cycles may be longer as treatments continue, to give the body time to recover. So the delay before the 7th cycle isn't surprising and a delay before the 8th cycle might be appropriate too. That doesn't mean that Vidaza has stopped working, but the timetable has to be adjusted to gain the most benefit.

As patients and caregivers it's hard for us to second-guess the doctors but the more questions we ask the more we can understand what they recommend. Please let us know what you learn from this next biopsy.

[Birgitta-A]

Hi King Farouk,
Wonderful that you have managed to get good examinations and treatment for your father! I don't think you should have any difficulties to get Neupogen when his WBCs are 1,4. Do you control his temperature every morning and evening? Be careful. Look at one of the sites for neutropenia. All infections will decrease all counts.

Then there is a warning list for lots of drugs and food that can decrease platelets: http://www.pdsa.org/about-itp/warnings.html

You know GSK har a special program for Promacta - http://www.promactacares.com/ and I still only know one MDS patient (Kirby Stone) who has received the drug outside trials. The drug has been approved in the EU (I live in Sweden) March 2010 and I still don't know if I can get the drug for my low platelets (last count 31). Hope you will manage and that your father will improve!
Kind regards
Birgitta-A

[King Farouk]

Originally Posted by Birgitta-A

Hi King Farouk,
Wonderful that you have managed to get good examinations and treatment for your father! I don't think you should have any difficulties to get Neupogen when his WBCs are 1,4. Do you control his temperature every morning and evening? Be careful. Look at one of the sites for neutropenia. All infections will decrease all counts.

Then there is a warning list for lots of drugs and food that can decrease platelets: http://www.pdsa.org/about-itp/warnings.html

You know GSK har a special program for Promacta - http://www.promactacares.com/ and I still only know one MDS patient (Kirby Stone) who has received the drug outside trials. The drug has been approved in the EU (I live in Sweden) March 2010 and I still don't know if I can get the drug for my low platelets (last count 31). Hope you will manage and that your father will improve!
Kind regards
Birgitta-A

Hello Brigitta, I have been following your posts for a while now and thank you for the list of platelets effecting drugs and food. I am extremely weary of his temperature and he is on prophylactics but last sunday, my American thermometer read 103 F and took him to the clinic right away and his temperature read 38.2 C slightly feverish and his doctor did not wish to take a chance and admitted him for IV antibiotics for a course of seven days which ends tonight. All cultures are clear so far. I have mentioned Neupogen but the Kuwaiti Doctor is still reluctant to start it out of concern that it may also activate the blast cells. His Absolute Neuts today are 0.3 and have not increased in the past 2 weeks and would certainly hate to go over the hospital exercise once more, Dad's Boston doctor is anxious to receive the results of the new bone marrow biopsy before proceeding with any recommendations. I will somehow try to eloquently direct their attention to Kirby Stone's experience and perhaps consider the Promacta and the Vidaza combination.

[King Farouk]

Originally Posted by Neil Cuadra

Since your dad still has low counts it would still be called bone marrow failure. But from your description the Vidaza treatments sound like a success. That's a huge drop from 27% blasts last October to 4% to 7% now.

It common with Vidaza that counts may get worse temporarily and that the interval between cycles may be longer as treatments continue, to give the body time to recover. So the delay before the 7th cycle isn't surprising and a delay before the 8th cycle might be appropriate too. That doesn't mean that Vidaza has stopped working, but the timetable has to be adjusted to gain the most benefit.

As patients and caregivers it's hard for us to second-guess the doctors but the more questions we ask the more we can understand what they recommend. Please let us know what you learn from this next biopsy.

You have exactly described what the doctors had thought about prior to the seventh cycle particularly when the BMB results showed the lesser counts and in fact the eighth cycle was delayed an additional 5 weeks and was administered with half of the usual dosage. The new BMB hopefully will provide more clues and will post the results once I have them. Thank you all for your interest.

[Birgitta-A]

Hi King Farouk,
You know my professor Eva Hellström-Lindberg, who is a very careful and well known expert in MDS, has found that Neupogen (GCSF) not increases the risk for leucemic transformation: http://www.ncbi.nlm.nih.gov/pubmed/18559873

When the latest BMB and all cultures are have been taken your father could start with Neupogen. All guidelines for MDS treatment recommend that instead of waiting for next infection perhaps with virus or fungi that are difficult to treat. http://emedicine.medscape.com/article/207347-treatment

Hope your father will get the very best treatment in the future too!
Kind regards
Birgitta-A

[King Farouk]

Originally Posted by Neil Cuadra

Since your dad still has low counts it would still be called bone marrow failure. But from your description the Vidaza treatments sound like a success. That's a huge drop from 27% blasts last October to 4% to 7% now.

It common with Vidaza that counts may get worse temporarily and that the interval between cycles may be longer as treatments continue, to give the body time to recover. So the delay before the 7th cycle isn't surprising and a delay before the 8th cycle might be appropriate too. That doesn't mean that Vidaza has stopped working, but the timetable has to be adjusted to gain the most benefit.

As patients and caregivers it's hard for us to second-guess the doctors but the more questions we ask the more we can understand what they recommend. Please let us know what you learn from this next biopsy.

As promised I am reporting the latest findings on my dad's case. The results of the new bone marrow biopsy indicate an increase in blast cells 20% and persistent Cytopenias as opposed to 7 % from the biopsy of Feb/10. The doctor is opting to switch to "Dacogen" and a myeloid growth factor. The little doubts start to appear on my head, weather the delay of the sixth cycle and the reduction of the dose of the seventh cycle has anything to do with that and if its an early judgment call to stop the Vidaza since it worked with great benefits for 6 cycles.

has anyone ran across a study where Dacogen is found to work after Vidaza since I understand the drugs somehow work the same and are used interchangeably ? I also read somewhere that Revelmid is also found to work in some cases even when -5q is not present. I wish I could convince the doctor to use them both but not sure if they counter each others effects.

I appreciate any shred thoughts and opinions on the matter.

[King Farouk]

Originally Posted by Birgitta-A

Hi King Farouk,
You know my professor Eva Hellström-Lindberg, who is a very careful and well known expert in MDS, has found that Neupogen (GCSF) not increases the risk for leucemic transformation: http://www.ncbi.nlm.nih.gov/pubmed/18559873

When the latest BMB and all cultures are have been taken your father could start with Neupogen. All guidelines for MDS treatment recommend that instead of waiting for next infection perhaps with virus or fungi that are difficult to treat. http://emedicine.medscape.com/article/207347-treatment

Hope your father will get the very best treatment in the future too!
Kind regards
Birgitta-A

Hi Brigitta,

I believe Dad will start getting Neulasta along on the sixth day of his chemotherapy (now switching to Dacogen, new BMB revealed increased blasts). Hope you are doing better and your platelets counts are getting better. Will look into the Promacta with the GSK pharma agent in Kuwait and maybe will luck out procuring it.

Good Luck and wish you the best.

H

[Birgitta-A]

Hi King Farouk,
Good with Neulasta!

Here is a report about Dacogen (decitabine) after Vidaza (azacitidine) with an overall response rate of 28%. The drugs work in different ways though both are DNA hypomethylating - decrease methylgroups that silence tumor suppressing genes. I posted a very complicated article about the two drugs a few days ago at "News...".
http://informahealthcare.com/doi/abs...28190701882146

About 25% of patients without the 5q- chromosome aberration respond to Revlimid. I don't think your father's bone marrow can tolerate both Dacogen and Revlimid - both decrease all counts in many patients.
Kind regards
Birgitta-A

[King Farouk]

Originally Posted by Birgitta-A

Hi King Farouk,
Good with Neulasta!

Here is a report about Dacogen (decitabine) after Vidaza (azacitidine) with an overall response rate of 28%. The drugs work in different ways though both are DNA hypomethylating - decrease methylgroups that silence tumor suppressing genes. I posted a very complicated article about the two drugs a few days ago at "News...".
http://informahealthcare.com/doi/abs...28190701882146

About 25% of patients without the 5q- chromosome aberration respond to Revlimid. I don't think your father's bone marrow can tolerate both Dacogen and Revlimid - both decrease all counts in many patients.
Kind regards
Birgitta-A

Hello Brigitta,

Thank you for leading me to that article on Dacogen after Vidaza and for the tip on revelmid. I am curious however, your profile does not indicate that you are using either Vidaza or Dacogen whilst your knowledge is incredibly vast on all the available treatment options?! are you considering a BMT in the future?

Perhaps you can make me understand how our doctors quickly concluded that Vidaza had stopped working and would not consider it further while it was the drug of first choice that worked beautifully. In my humble non medical thinking I am suspecting that due to the persistent cytopenia, it induced a five week delay of the seventh cycle and ultimately reduced its dose. Could this make up a reason for the increase in Blasts and disease progression as shown in the latest BMB and be simply described as "vidaza starved" or its just not that simple?

Dad is proceeding to follow the doctors opinion and starting Dacogen tomorrow given both doctors on opposite corners of the world had reached the same conclusion. but i just cant help but wonder given what we had gone through the past year.

I sincerely wish you the best of luck and hope you will beat this disease and if there is anything I can help from our part of the world please don't hesitate to let me know.

[Birgitta-A]

Hi King Farouk,
You are right about my treatment - since I am very afraid of adverse effects I only accept supportive treatment. I had severe marrow fibrosis from dx May 2006 (I had probably had MDS for years) and I don't think my bone marrow could tolerate Vidaza. As a matter of fact Vidaza is only approved for high risk MDS in the EU and I still have MDS Interm-1.

Stem cell transplantation has never been an option for me because I was 67 yo at dx and as far as I understand low age is a very important factor for a good result.

I am still asymptomatic and I am thankful for every day i can continue with transfusions, Desferal, Exjade and Neupogen. Even if my life won't be much longer I prefer high quality of life.

You know nobody really knows how Vidaza should be dosed according to my doctor who is a specialist in Vidaza treatment in MDS patients. It is common to evaluate the result after 6 cycles. Perhaps it is better to try another drug after 6 months if the blasts have increased and counts decreased. It is probably not possible to know the reason for the increased blast cells.

Thank you for offer about help - I am very interested in your contacts with GSK about Promacta/Revolade.
Kind regards
Birgitta-A

[King Farouk]

Originally Posted by Birgitta-A

Hi King Farouk,
You are right about my treatment - since I am very afraid of adverse effects I only accept supportive treatment. I had severe marrow fibrosis from dx May 2006 (I had probably had MDS for years) and I don't think my bone marrow could tolerate Vidaza. As a matter of fact Vidaza is only approved for high risk MDS in the EU and I still have MDS Interm-1.

Stem cell transplantation has never been an option for me because I was 67 yo at dx and as far as I understand low age is a very important factor for a good result.

I am still asymptomatic and I am thankful for every day i can continue with transfusions, Desferal, Exjade and Neupogen. Even if my life won't be much longer I prefer high quality of life.

You know nobody really knows how Vidaza should be dosed according to my doctor who is a specialist in Vidaza treatment in MDS patients. It is common to evaluate the result after 6 cycles. Perhaps it is better to try another drug after 6 months if the blasts have increased and counts decreased. It is probably not possible to know the reason for the increased blast cells.

Thank you for offer about help - I am very interested in your contacts with GSK about Promacta/Revolade.
Kind regards
Birgitta-A

Hello Brigitta,
Dad will finish the last dose of the first cycle of Dacogen Tomorrow and he seems like he tolerated it well and no apparent adverse effects. He will also take his Neulasta shot 2 days later according to the program prescribed by Boston doctor. However, if the treatment works am not sure if we would expect the counts to go up again like it did before somehow I suspect the function of the bone marrow got stuck and the myeloid suppression that had occurred after the 6th cycle of Vidaza was irreversible. I believe the condition is termed persistent cytopenia that also known to confuse speculation of disease progression versus response to treatments prior to a BMB of course.

I should also mention that I spoke to the Kuwaiti doctor about Promacta as instructed by the GSK Rep. He indicated that Kuwait Cancer Center doctors can have direct access to the drug to treat ITP even if its not registered by the Ministry of Health (which is not so far) and could be procured to the patient as long as they are Kuwaiti nationals. He was reluctant to approve it in my dad's case saying that usually there are adverse effects like increased stroke potential and Myeloid fibrosis however he did not show a very strong reservations against trying Nplates indicating that there might be a second phase results trial on use with MDS patients and left it like that. How does Nplates compare to Promacta?

Also could you please let me know, if anyone in the forum you have encountered has been treated by Dr Azra Raza from St. Vincents in New York. Apparently she is a world authority on MDS and I was thinking of getting in touch with her to illustrate my dad's case. I want to be prepared for the next step.

Best Regards,

H

[Birgitta-A]

Hi King Farouk,
Good that your father didn’t have any adverse reactions to Dacogen !

You know we can manage quite well with cytopenias with packed red blood cell transfusions, Neulasta and Promacta for the three cell lines.

There are more reports from trials in MDS patients with Nplate than with Promacta. Here is one of them: http://ash.confex.com/ash/2009/webpr...aper19357.html.

The drug can increase blast cells. FDA has a special warning about Nplate (page 11): http://www.accessdata.fda.gov/drugsa...8s000_sumR.pdf

There are two trials with Promacta in MDS patients and the first one will be completed during the fall 2009. Otherwise there are only trials in tubes. This study shows that Promacta can decrease leukemic cells: http://www.ncbi.nlm.nih.gov/pubmed/19710504

Both drugs can increase bone marrow fibrosis.

If you search at Raza at Marrow forums you will find a lot of posts (very positive) about Dr Azra Raza.
Kind regards
Birgitta-A

[King Farouk]

Originally Posted by Birgitta-A

Hi King Farouk,
Good that your father didn’t have any adverse reactions to Dacogen !

You know we can manage quite well with cytopenias with packed red blood cell transfusions, Neulasta and Promacta for the three cell lines.

There are more reports from trials in MDS patients with Nplate than with Promacta. Here is one of them: http://ash.confex.com/ash/2009/webpr...aper19357.html.

The drug can increase blast cells. FDA has a special warning about Nplate (page 11): http://www.accessdata.fda.gov/drugsa...8s000_sumR.pdf

There are two trials with Promacta in MDS patients and the first one will be completed during the fall 2009. Otherwise there are only trials in tubes. This study shows that Promacta can decrease leukemic cells: http://www.ncbi.nlm.nih.gov/pubmed/19710504

Both drugs can increase bone marrow fibrosis.

If you search at Raza at Marrow forums you will find a lot of posts (very positive) about Dr Azra Raza.
Kind regards
Birgitta-A

Brigitta,

Thank you for the wealth of information you are sharing with us.

Regards,

H

[rose mcmillin]

Hi Hope that your Dad is improving. My husbands numbers dropped and his platelets are now just 25. Not sure what the new plan is, we will find out next Monday when we see the doc. We were off Vidaza for 6 weeks then the doctor decided to try it again and it tanked his numbers. Just waiting to see the next step.Any suggestions would be so appreciated. Thanks, Rose

[King Farouk]

Originally Posted by rose mcmillin

Hi Hope that your Dad is improving. My husbands numbers dropped and his platelets are now just 25. Not sure what the new plan is, we will find out next Monday when we see the doc. We were off Vidaza for 6 weeks then the doctor decided to try it again and it tanked his numbers. Just waiting to see the next step.Any suggestions would be so appreciated. Thanks, Rose

Dear Rose,

Hope you are well. Most likely and hopefully your husband's marrow is only what they call being Myeloid suppressed due to the combination of disease and treatment. At this point the doctor will most likely suggest a Bone Marrow Biopsy a few days before the date of the new cycle and if I were you I'd insist on it, by doing that it solves part of the puzzle. If the results indicate a lower number of blasts than when you started during the diagnosis then Vidaza treatment is successful and although the transfusion independence may soon go and may not be reversible very soon, the doctor will most likely continue the Vidaza by reducing the dose or delaying the cycles or a combination of both. After trying that approach for 1 or 2 cycles (delay or reduction of dose) and if the counts do not recover they will suggest another Bone Marrow Biopsy to determine if the blast cells had increased from the 2 months or less prior. If no increase in Blast cells are present in the biopsy then they will most likely continue treatment with Vidaza. The persistent Cytopenia will be dealt with through RBC transfusions, platelet transfusions (perhaps direct family donors with group specific is ideal and lasts more) and Neupogen shots to increase white cell production. The Vidaza will continue to control the blast cells and the disease progression until further notice. I would not stop the vidaza unless there is a clear evidence that the marrow is no longer responding since once you are off of it, the next defense is Dacogen which has about 28% percent chance to work after Vidaza treatment according to a study and this is what my father had started last week. After that it is low dose Ara-c, cholorafarabine or Mylotarg and all of them have more serious adverse effects than Vidaza and Dacogen>

The above is a summary of our doctors opinion and hopefully it gives you sufficient discussion points to have with your husband's doctor.

Wish you the best and let us know what they say on Monday.

H

[rose mcmillin]

Hi King Farouk, Hello and Thankyou for your suggestions. I have discussed them with my husband and we plan to talk to his doctor on Monday. Maybe I have been a little lax about demanding answers from the doctor. It seems like there are so many variables and I don't think anyone can truly predict much. I hope this post finds your Father doing better. This disease is so complicated. Be strong, and I wish you the best. Rose

[crpa]

Hi:

I am glad to read about your Dad's success with Dacogen treatment.
My husband will be starting a treatment regimen with Dacogen soon after a
bad experience with Vidaza due to bad liver #'s
He has since been back home after 41 days in hospital from chemo treatments to get blasts down to 6 % from 30% ( aml) a couple months ago.
Very scary time but we both are glad to be home.

Thanks for posting your Father;s progress it is good to hear how others are battling this disease.
Good luck in your treatments
Sincerely,
CC

[anita s]

My husband has MDS RAEB II treated at Hershey Medical Center with stem cell transplant by Dr David Claxton, doing fantastic since transplant in June. I would contact the staff and make and appointment there.