MDS/RCUD - need help in treatment option

[ccnarayanan]

My father, nearing 83, is diagnosed with MDS (currently affecting RBC/Hb, so RCUD). His PRBC transfusion requirement is around 1.5 units (450ml per unit) per month in the last 6 months.

He has monosomy 7, del7q31@18%, del20q@52%. Erythroblasts are at 2%. His IPSS score is 1 / Intermediate-1.

The doctors tried B12, folic acid, and iron supplements until about a month ago, prior to MDS diagnosis.

His serum B12, serum folic acid, and ESR levels are high. Ferritin level has not been evaluated.

He has done 7 transfusions in the last 6 months. His current Hb is 6.5. Now the doctor has ordered 2 units.

In the last two weeks, he has been on Darbepoietin alfa (Aranesp); took the third injection today. He started it at Hb of 7.3 and now his Hb is 6.5 (hence the order for 2 units of PRBC). His serum erythropoietin level before starting this was 70.1 IU/L (range being 5-30 IU/L).

The doctor has talked about Decitabine (Dacogen) on 1-5d/28d treatment regimen.

Now the questions:
- How long will it take for Darbepoietin alfa / Aranesp to show improvement on RBC/Hb? What are the merits and risks in continuing with it as opposed to starting Decitabine now? Our primary hematologist (more experienced and affiliated to a bigger hospital in a metro) wants to see the response of Darbepoietin alfa / Aranesp whereas the other hematologist in a big hospital in my father's home town (a smaller city) suggests starting Decitabine with or without Darbepoietin alfa.
- What is the most appropriate treatment option at the moment? Continue with Darbepoietin alfa or start Decitabine?

Thanks!

[Birgitta-A]

Hi ccnarayanan,
Good that your father's EPO initially was as low as 70. Patients with EPO less than 500 are responding better to EPO drugs like Aranesp. Here are recommendations from the Nordic MDS Group: “In general, start with Epo alone for 8 weeks. In case of no response add Neupogen or a similar drug for another 8 weeks.”

You know monosomy 7 and del7q31 are not good chromosome aberrations. Most doctors advise starting active treatment at once for example with Dacogen or Vidaza (Vidaza is actually the first drug).

When you start for example Dacogen treatment your father's HGB will probably decrease initially so it will be impossible to know if Aranesp has any effect.

Perhaps it will be OK to wait some weeks for the Aranesp response.
Kind regards
Birgitta-A
75 yo, dx MDS Interm-1 2006. Chromosome aberrations -12p and -X. EPO initially more than 800 so I never got an EPO drug. Supportive treatment with txs, iron chelation and Neupogen for low WBC until 2010. 2010-2013 Thalidomide with positive effect. Now Revlimid with good response.

[Mseth]

Hi CCNarayanan,

My mother has a similar diagnosis as your father, though she has cytopenia(low count) in the red cells only, her bone marrow showed dysplasia in all 3 lines, therefore RCMD diagnosis.
I would agree with Birgitta-A's advice to try aranesp for few weeks, given his low initial epo level, he may respond. Decitabine is a harsh treatment, and as I understand we do not have the option of Vidaza treatment in India.
When a patient gets blood transfusions, we do not get to know the patients own Hb level correctly. Has his blood transfusion requirement increased over last 6 months? Given his age and not-so-high transfusion requirement, I would like to understand what makes your doctor suggest Decitabine. Is it because of the monosomy 7 and del7q31 or is he seeing a progression of the disease?
Do keep us posted on the progress. All the best.

[ccnarayanan]

Thanks, Birgitta-A and Mseth for your inputs.

My father had two PRBCs yesterday which somewhat refreshed him.

Mseth, regarding your questions - we have been tranfusing only in the last six months triggering transfusion at various Hb levels, so we don't know if transfusion requirement has changed. The doctors did mention that they are worried about monosomy 7 and del7q31 and probably that is why they are suggesting Decitabine.

We are planning to consult the doctor after 4 Darbepoietin alfa/Aranesp administration and seek advice on whether to continue it or go for Decitabine.

Thanks!

[Mseth]

Hi CCNarayanan,

Hope he will respond to aranesp!!

You can keep a record of date of transfusion, pre-transfusion Hb and units transfused. This will help you track the transfusion requirement over a period of time. In transfusion dependent patients, since we can't really see the actual Hb levels even if the interval between 2 transfusions increases we know that the darbapoeitin is helping.

[ccnarayanan]

My updated signature says it all ...

[Birgitta-A]

Hi ccnarayanan,
How sad that your father has such a severe disease. We can only hope that Decitabine will have effect.
Kind regards
Birgitta-A

[ccnarayanan]

Now the IPSS score has changed from Int-1 (1) to Int-2 (2). But, considering his age, according to the hemato-oncologist, the medical management option remains the same - that is, Decitabine.

In the last two days, he has been eating better and the doctors and nurses are urging him to sit on a chair during day time. He has had two 20mg (13.33 mg/m^2) infusions of Decitabine per day. Fever is subsiding and he is feeling a little better, but still on anti-emetics, antipyretics (this time, only tablets), and low doses of sedatives. The sedatives are occasionally driving him to some delirious world. The hemato-oncologist feels the fever should probably go away with the third dose of Decitabine. He is still nearly completely immobile. The physiotherapist is providing his services to get him move around.

Now the question - does MDS result in rendering the patient permanently immobile? He has been an ostereoarthritis patient for the last 15-20 years with his weakness around knees, but now he is not even able to lift himself from the bed. He has been moving around well until two weeks ago, but now, someone needs to lift him even to change his position on the hospital bed.

[Birgitta-A]

Hi ccnarayanan,
Good that your father is better !

You know fever and low HGB will give weakness. Sedatives can lead to weakness in muscles especially drugs like Valium. Perhaps your father could manage with a lower dose of sedatives?
Kind regards
Birgitta-A

[Mseth]

Hi CCN,

Great to hear that your father is doing better. He has been on antibiotics for a long time, that is bound to cause weakness. As he recovers he should get his energy back thought it may take a while.
How are his counts after Decitabine has been started? Its great that he has been able to tolerate it. The decision to start Decitabine was very timely.
I have no understanding on whether MDS can cause immobility, or how Decitabine can take care of fever. I suppose these are all indirectly linked.

All the Best!!

[ccnarayanan]

Decitabine started at Hb of 8.0 and PLT of 36000. After one day, Hb was 7.6 and PLT was 48000. After 4 injections (total of 65 mg), Hb is now 7.6 and PLT, 51000. Blood was hemodiluted to begin with (due to electrolyte infusions). Hard to figure out if Decitabine had any effect ...

[Birgitta-A]

Hi ccnarayanan,
You know Decitabine (like Vidaza) is working when the stemcells are dividing - this means that it takes several cycles before the drug will lead to improvement. It is common that all counts decrease initially.

Hope the drug will start to increase your father's counts soon!
Kind regards
Birgitta-A

[Whizbang]

ccnarayanan,

Definitely takes 2 - 5 rounds of Dacogen for full effect...

I was in full (MDS) remission after two rounds...

1st round all of my counts went down...

All the best...

[ccnarayanan]

Today, the family had a 30-minute briefing by the medical team. It was organized with extreme professionalism, honesty, openness, and sensitivity by the hemato-oncologist and the Director of Getriatrics. We had prepared a few questions, but they had already answered most of the questions in their briefing. To my query on CPR, the Director of Geriatrics said there are ethical issues involved in giving CPR - sometimes, the heart resuscitates but not the brain and this results in a vegetative state which makes things far more complex; in such situations, bring him to the hospital which is a couple of miles away. According to him, if there is natural degradation of the body and if it decides to stop responding to intervention, it is best to let it go.

They have given two back-to-back transfusions with no donors asked for. The hemato-oncologist was extremely supportive and helpful; he had called the blood bank manager to release the blood with no questions asked. He himself provided contacts of the nursing services (the euphemism for hospice care in this part of the world). He told me privately about my dad's condition today - these could be his last days, please engage a good nursing service to make his life comfortable during this time.

[Caregive]

ccnar, I am with you. My husband is almost 82 and doing very well with some unrelated conditions adding to the picture. He gets discouraged but we keep all his medical appts and go from there. He is active and aware and alert but knowing this could be a long struggle here on out. So international prayers to and from us all. Keep us posted.

[ccnarayanan]

Hey, thanks for your kind words. It gets difficult with increasing age and many unrelated problems trying to act together.

[ccnarayanan]

Yesterday, there was an urgent requirement for platelet transfusions since the counts went below 20000/mcL. The hospitals here don't keep platelets except for ICU. I arranged for a donor and they took 5 "units"/cycles through apheresis from the donor and transfused to the recipient.

In the last two days (even before platelet transfusion), my dad is looking fine. He is awake from his seemingly unending sleep and is quite alert.

He was discharged today and back home in an ambulance. His mobility has improved; he can turn around on the bed, not yet get up on his own. He is talking and coherent. He keeps moving his hands and legs to give some exercise to his joints. The hospital has implanted a silicone (?) catheter to help with the urine removal (the catheter can be kept for about 3 months and requires cleaning once a day).

Tomorrow, the nursing team will report to work.

[ccnarayanan]

My dad passed away peacefully on Sunday afternoon from home in the presence of family members.

I want to appreciate all help, guidance, and support provided by various members in this forum.

[rkp]

Very sorry to hear this.
May the Almighty give you and your family strength to get through this difficult time.

[Neil Cuadra]

ccnarayanan,

I'm very sorry that you lost your father to MDS. It sounded like he got excellent care from both doctors and family, with your studious research being a big part. I hope he found comfort in the care, and in being at home with family.

Thank you for helping other patients here even as you were helping your father.

[Birgitta-A]

Dear ccnarayanan,
How sad that your father passed away. It is good to know that his dr was extremely supportive and helpful like the whole team that supported your father during his disease.
Warm regards
Birgitta-A

[Cheryl C]

Deepest sympathy for the loss of your father, ccnarayan. I have often admired the concern and attention you have given to doing your very best for him. May God comfort you and your family as you deal with your sorrow.

[bhasky]

CCN
My deepest sympathies to you and your family.
I am based out of Bangalore and my father lives in Kolkata. He has been diagnosed with MDS resulting primarily in neutropenia and also low Hb levels.
Supportive therapy with Erythropoetin and GM-CSF was working for him for about 8 months, but recently his WBC levels have started diving although they are not yet at levels where he will become febrile.
Can you please tell me or send me a message where you were getting your father treated, so that I can explore getting the next level options like Decitabine made available to him. So far it has not been suggested, and he is being asked to go on a more frequent dosage of the supportive therapy mentioned above.
Also regarding Vidaza I saw a research paper published from JIPMER Pondicherry about the same, was that ever offered ...perhaps it is available somewhere in India.

Thank you so much for your help...

[Mseth]

Hi Bhasky,

Sorry to hear about your fathers mds diagnosis.

As you may know Decitabine is the generic form of dacogen available in India. I am told by the doctor that dacogen can also be imported and so can Vidaza. Of course the costs will be very different with Decitabine being the lowest followed by dacogen and then Vidaza. I do not remember the exact cost quoted to me but the import cost was quite steep. Decitabine shud be available in Kolkata as well.
If there is response the drug is continued on a monthly basis. Decision to start these therapies will be decided by the doctor on the basis of his risk category.

Where in Kolkata is your father being treated?

[bhasky]

Thank you Mseth.
I will wait to see if those options are offered in Kolkata and then decide to consider other locations if that does not happen.
He was initially treated at Apollo and then he is being treated at home by a private Physician (once the supportive therapy started working)