EPO+Gcsf
 

Hello forum members,

My mother had not responded to Eprex 40,000/week, given for 8 weeks. The doctor did not feel the need to try an increased dose. Now on my insistence, he has agreed for higher dose Eprex 60,000 weekly, with addition of G-csf weekly 300 from week 3. She starts neupogen next week. Any personal experiences with this combination or anything to watch out for? Any views on whether the Eprix and Neupogen be given on the same day or spaced out in the week?

Any new treatment gets me very hopeful but also worried.

Thanks.

My husband Paul was on G-CSF and EPO jointly for 8 months commencing almost immediately after diagnosis of hypocellular MDS and in the lead up to his MUD transplant. He had three neupogen injections per week, and started treatment with two EPO injections. The EPO was lowered to once weekly and then once fortnightly because he was responding so positively. This treatment kept him asypmtomatic of the disease at all times. At diagnosis his bone marrow was only only producing all of the three blood lines at a very low percentage of the normal range. However with this treatment his blood cells lifted well inside of the normal range.

You have to remember that even if there are positive results, that this medication is a bandaid and can stop working at any given time.

From what I have been told and also read, using the two together gives better results than using either on their own. However, I have also read that only about 30% of patients using these medications shows positive response.

I understand that these types of medication are not commonly used in patients with hypercellular MDS as there are suggestions that it might increase the blast cells.

Sometimes these injections coincided - he had control as he was self injecting and preferred it if he did it at the same time. This was fine with his consultant.

Hope this is helpfull.

EPO+Gcsf in hypercellular marrow
 

MDSPerth, thanks for responding and highlighting the marrow connection.

My mother has hypercelluar marrow. I have not found any study where there is reference to the marrow(hyper/hypo) in regards to response or use of growth factors. I have read threads on this forum where Gcsf has not been prescribed due to fear of increasing blasts but again not found any studies on this or in connection with hypercelluar marrow.
As I understand, EPO alone and with addition of Gcsf is the first line of treatment of anemia in low risk MDS.

I am worried about the increase in blasts and hypercellular marrow. Is it going to be a big risk?

Pauls situation was quite different to hypercellular marrow. What he was producing were reasonably healthy cells, he just was not producing enough of them (so to use treatments like vidaza etc. would not have suited him, it would have killed off the healthy cells he was producing) Therefore, the growth hormones (or transfusions) were the only treatments open to him. As far as transfusions go, this is fine for RBC or platelets, but you cannot transfuse white blood cells. Pauls white blood cells, hence his neutrophils were the worst ones affected - at the time of diagnosis they were 0.25. His diagnosis was as at the higher end of Intermediate 2/lower end of High risk, and he was 61 at that time.

My understanding of MDS is that it is a clonal disease, therefore the unhealthy cells tend to multiply themselves. Hence if growth factors are used, you run the risk of the unhealth cells multiplying themselves out faster than perhaps they would have done, hence the risk of increasing blast cells (which are immature red blood cells).

The above is only my understanding after reading and discussions with the doctor, I may have it wrong, but what I can say is that everything I have read and discussed with the doctor indicates that the two growth factors used together shows better results.

Good luck with your mum for her treatment. Its a very worrying time!

Hi MSeth

My biggest problem is white cells and especially neutrophils. Mostly my ANC puts me into the severe neutropenia category. However my well-respected specialist in Sydney would not prescribe growth factors as I don't have zero blasts, and he believes that GSF could increase blasts. If your Mum has zero blasts it might be different.

FYI there is a clear explanation about what blasts are on http://lymphoma.about.com/od/glossar...last-Cells.htm

It's great that you are so involved and concerned about your mother's treatment.

Blasts/growth factors
 

MDSPerth, it is indeed a worrying time. Do you know if there is any bone pain after the Gcsf shots? Surprisingly, I am still unable to find any study/information connecting marrow cellularity with the use of growth factors.

Cheryl C, I so wish that my concern and involvement could result in a positive outcome for her, in her case a higher Hb or atleast longer transfusion intervals. Thanks for the explanation on blasts. How do you handle your neutropenia without Gcsf?

There seems to be no treatment for MDS without many associated risks. At this point, she feels fine, and is able to stay active and eat well with the once in 3 weeks transfusions.

Even though she has RCMD, her whites and platelets are stable, well within normal range, its her rbc/hemoglobin which is the bothersome one. She is low risk, <1% blasts as per BMB in May'13. The doctor said we could expect to see TLC counts of as high as 25 once she gets neupogen, which may reduce in the week but then it would be time for next nepogen shot. Though he has prescibed it on my insistence, he is not hopeful of any result(he does not tell me why) which makes it more difficult for me. However, the EPO+Gcsf combination is supposed to have a 30%-40% response and is the standard treatment for low risk anemic MDS.

Best wishes, stay well and Sorry for this long post!!

Hi Mseth - I handle my neutropenia by a healthy diet (plenty of fruit and vegies, no alcohol, no smoking, no meat except fish occasionally, no dairy, no cane or other sugars except fruit and natural unheated honey), strict hygiene (especially hand-washing) and taking Echinacea 5000 mg whenever I feel as though I might be getting a sore throat. I take Vitamin D every day. For skin wounds I use peroxide promptly if they look as though they might infect.

I think that the gamma globulin I have every month for hypogammaglobulinemia is also helpful for my immune system. It is extracted from plasma.

I do hope that the EPO/GCSF will be of great benefit to your mum as red blood transfusions can cause problems with excess iron over time. God bless you as you continue to seek ways to assist her.

Hi Cheryl C,

Yes, the best way is through diet & nutrition, and if it can be managed with limited drugs. I think over a period of time, everyone has to figure out the balance that works for them and stay with it till it works!!

Stay well!!

Hi all,

The neupogen shots did not have any side effects of associated pain/fever that i had feared. Now just hoping that it helps alongwith Eprex to stimulate the bone marrow to make some good RBCs.

Neupogen has already increased the white cells(which were not required as they are in normal range), why are the red cells so difficult? They dont seem to move upwards.

It can take up to 8 to 12 weeks to see significant improvement. Did you know what her EPO level was before starting the injections? Usually, many who are anemic, have a very high EPO level (over 500) and therefore do not respond to it.

EPO response
 

Marlene, her pre-treatment EPO was 126. Doc says 6-8 weeks is enough to see if she will benefit from it. This is the 2nd try with EPO, at a high dose of 60,000 weekly, and neupogen added from week3.
As she is transfusion dependent, response will be seen in terms of longer transfusion intervals/lower hb drops. After starting EPO, she had a drop of 15 points in the first 24 days and then suddenly 10 points in last 7 days. So dont know what to make of whether EPO is having benefit or not. She has also started with Vit K2+D3 in the last few weeks. Hope there is some collective benefit of the 2 therapies together.

I would hope with that EPO level she should have some benefit. I think John did a 40,000 dose each week. It did help him get transfusion free a bit faster but at some point, there was no longer a benefit so he stopped it. He was finally at a point where his BM was able to maintain things without it.

Marlene, how many weeks of EPO did John take to see even the smallest response, if he was transfusion dependent at that time, did you see response through longer intervals or were you able to see a rise in HB? It must be many years ago for John, but would like to understand what the trend may be like.
Hope John is doing well, its nothing short of a miracle for the BM to start functioning again.

I didin't put all the events on the tracking spreadsheet I made but from what I can recall this is how it went down:

1) We had his EPO levels checked on 8/22/03. They were at 96
2) He didn't start Procrit until his retic % was at 2 - 2.5%. This was based on input from our doc at Hopkins. That was January 2004
3) He started 40,000 units of procrit/weekly on 2/9/2004.
4) His last transfusion was 4/11/2004

The improvement came in the second month. He was getting red cells (two units) every two weeks until 3/22. So on 3/22/04 he got a red cell transfusion and went 3 week before needing another. On 4/11, we decided to do just on unit of red cells and from then on, he did not need anymore.

So the response was seen in the interval versus the actual HGB. You can also look at retic% and Absolute retic count.

Retic%
 

Thanks Marlene, for taking the time to give me the details, and sorry for making you go so far back in time.

My mothers retic% in April 2013, just before diagnosis was 2.7% (normal 0.5-2.5). Absolute retic number as per an online caluclator(taking into account hct) was 1.54. The doctor has not asked for it again. I will have it checked at next cbc, but i wish we had the results of the last few months as well to track.

If you have your absolute retic count, can you calculate the % ? I wasn't given mine in %.

Thanks,
Deb

Retic count/%
 

Deb, we get our reports only in Retic %. I think Absolute count is more relevant than %, something like ANC is more relevant than Neut%.

Since I am trying to understand what this means for MDS, I found this formula for converting to Absolute Retic Count:
www.mdcalc.com/absolute-reticulocyte-count-index
Absolute Reticulocyte Count = # or % retics * (Pt's Hct / Normal Hct)
So for calculating %, it will be Retic % = Abs Retic *(Normal Hct)/Your Hct

Also, as per this link
http://en.wikipedia.org/wiki/Reticulocyte_index
Raw Retic Count is misleading in anemic patients, and therefore a correction factor is to be applied as mentioned in the link.

Its all very confusing to me as of now, and other than the Retic %, all numbers for my mother show well below normal, i guess thats why she has MDS.

Update
 

Hi all,

I finally have a trend of how the transfusion interval increases with weekly Eprex shots. While my mother was receiving Eprex 60,000 weekly in Oct & Nov 2013(8 weeks), transfusion interval increased from earlier 20-21 days to 28-30 days. As the increase was not very significant, Eprex was discontinued and the interval is back to 3 weeks now.
Can anyone please advise on whether it is worthwhile to have weekly high dose Eprex 60,000 to gain 8-10 days additional on transfusions. Both transfusions and eprex seem to have their own negatives.
I am yet to meet the hematologist after these readings.

Thanks for any suggestions and advice on this.

EPO
 

Hi Mseth,
It is true that the increase in tx intervals not was very significant but still it is better to have txs every 4th week instead of every 3rd week.

Did your mother have any adverse effects from Eprex? If not I should prefer to continue with Eprex.
Kind regards
Birgitta-A

Hello Birgitt-A,

Yes, the 4th week tx was actually a big relief, the additional 1 week gives so much additional peace as well. Just wary of the side effects of the high dose of 60,000. She did not face any problem, other than 3 needle pricks(40+10+10) weekly.

She plans to give another try with Lenalidomide, as earlier she was unable to tolerate beyond 3 days. Does erythropeitin enhance the effect of Lenalidomide, and can the 2 be taken together for better results?

Thanks for taking time to respond to my post and many questions.

Revlimid + EPO
 

Hi Mseth,
Revlimid + EPO has showed better results than Revlimid alone.
http://www.mdsbeacon.com/resources/m...013/abs/s1107/

Remember that Revlimid alone can give thrombosis and that EPO eventually increases that risk.

I asked my doctor if I could take Prednisone too when I started to take Revlimid July 2013 though I was aware of that Prednisone could increse the risk for DVT. I got a DVT in my left leg and now I have to take an injection of Innohep (heparin that decreases the ability of the blood to coagulate) every day.

I started with 5 mg Revlimid 21 days of 28. After 2 months we increased to 5 mg/day. I tolerated the drug very well (except for the DVT) and after 3 months we increased to 10 mg 21 days of 28. Then I responded and since Nov 2013 I have been tx independent :). My HGB is now 11.8 and my platelets 135 (very good for me).

Remember that your mother should start with a VERY low dose of Revlimid. There is no hurry. You managed to let her start with a very low dose of Exjade and that has been positive.
Kind regards
Birgitta-A

Birgitta-A, I am very happy to hear that you responded to the revlimid so well, that is a good sign. Your counts look great! so you must be feeling very good. I am happy for you.

Hi Birgitta-A,

Thanks, I will follow your advice on a slow start for Lenalidomide.

For now, the epo weekly shots are being restarted.

Thanks for taking the time to respond, really appreciate.

Revlimid
 

Hi Mseth and skb007,
It is true that I feel fine but as a matter of fact I don't feel much if the HGB isn't going as low as 7.0. Then I can get breathless in stairs and steep hills.

I am very thankful that I am responding - I responded almost 3 years when I took Thalidomide but I dare not hope for such a response when I take Revlimid.
Kind regards
Birgitta-A