Neulasta

[Bobbye A]

Ruth,

Do you know if Neulasta is ever given to patients who have never had chemo? Nupegene did my sister no good at all and were afraid to give it to her any longer for fear of messing up her red counts and platlets. So far her reds, etc. are good but no detectable neutrophils [puzzling]

Bobbye

[skoopman]

My daughter had Neulasta which was described to me as a longer lasting Neupogen. Neupogen you have to get daily, Neulasta was once a week. She had AA so was not producing any blood cells. In her case it didn't make any difference in production, or lack thereof. I hope it works better for you.
Suzanne

[Ruth Cuadra]

Originally Posted by Bobbye A

Do you know if Neulasta is ever given to patients who have never had chemo? Nupegene did my sister no good at all ...

Hi, Bobbye.

Neulasta (pegfligrastim) is a long-lasting version of Neupogen (filgrastim). Both are made by Amgen, Inc. As far as I know, they can both be used with and without chemo. The advantage of Neulasta is that it doesn't have to be administered as often. However, Neupogen may be a little less expensive.

Regards,
Ruth

[lddorazio]

I was treated with dacogen and thought i was doing well. but had low wbc. Got a shot of neulasta at 9:30 am and ended up in the emergency room at 10 pm. severe reaction to Neulasta. Speny 30 days in the hospital and 6 days in rehab. Still have not recovered. Neulasta is for severe doses of chemo and has not been through most clinical trials. Make sure you check all the bases.
Len

[Bobbye A]

Originally Posted by lddorazio

I was treated with dacogen and thought i was doing well. but had low wbc. Got a shot of neulasta at 9:30 am and ended up in the emergency room at 10 pm. severe reaction to Neulasta. Speny 30 days in the hospital and 6 days in rehab. Still have not recovered. Neulasta is for severe doses of chemo and has not been through most clinical trials. Make sure you check all the bases.
Len

Len,
Thanks for the tip, sorry for all your complications, hope you have the upper hand by now. Hang in there, it has to get better, right???
Bobbye

[DomesticDeeva]

My 11 year old daughter is currently undergoing immunosuppressive drug therapy to treat her very severe aplastic anemia (she was diagnosed at age 10 in Feb 2008). Her current drug regimen consists of daily prednisone, daily cyclosporine, and weekly neupogen injections. She has had no adverse reactions and her neutraphils (WBC) greatly increase within the first 48 hours of the injection and then begin to decrease until her next injection with an overall trend of her counts moving upward every so slowly. She was given Neulasta (the longer-lasting version of Neupogen) initially, however, our insurance would not cover it and we had to go back to using Neupogen (Neulasta cost 4x as much). Neupogen is also very costly and we were able to qualify for Amgen's Pharmacy Replacement Program with the help of the case worker at Sacred Heart Children's Hospital. If you have any questions at all about Neupogen and it's potential short term and long term effects on your specific diagnosis, I recommend you discuss them in detail with your oncologist. My daughter has not undergone chemo and since she is overall responding fairly well to immunosuppressive drug therapy, she will not need a BMT at this time. Hope this helps.

[sandra]

Hi Shana and Matt,

Can you clarify something for me please?

1. Why do you say that Haylee did not get chemo so far? Didn't she get the ATG (horse serum) upon being diagnosed with vSAA? Do you still have a record that shows her counts at diagnosis (WBC, HGB, PLT, ANC, and MCV)?

2. Why is she getting the Neupogen shots? Is her ANC dipping below 200 (or 0.2) within a week from the shot?

3. Are you actually saying that she's on DAILY prednisone since February??!! How many miligrams?

Sandra

[DomesticDeeva]

Originally Posted by sandra

Hi Shana and Matt,

Can you clarify something for me please?

1. Why do you say that Haylee did not get chemo so far? Didn't she get the ATG (horse serum) upon being diagnosed with vSAA? Do you still have a record that shows her counts at diagnosis (WBC, HGB, PLT, ANC, and MCV)?

2. Why is she getting the Neupogen shots? Is her ANC dipping below 200 (or 0.2) within a week from the shot?

3. Are you actually saying that she's on DAILY prednisone since February??!! How many miligrams?

Sandra

Hi Sandra,
Thank you for the questions. Here are my responses corresponding to your numerical bulletpoints:

1. My understanding is that ATG is not a form of chemo. Yes, Haylee did receive one round of ATG immediately upon diagnosiss of VSAA. This eventually helped to increase her RBC, HCT, and ANC. Yes, I have all of her counts upon diagnosis as well as every count taken since then. I maintain a chart to track her overall trend and effectiveness of her current drug regime. Her initial counts back in Feb were roughly: ANC = 10, HCT = 20%, PLT = 10,000. She has been transfusion-free for approximately four and a half months and her more recent counts are roughly: ANC = 1200, HCT = 26%, PLT = 50,000. What does "MCV" stand for?

2. Haylee's oncologist has prescribed weekly Neupogen injections until the end of September when her counts will be taken again. At that time, he will consider taking her off of Neupogen and tapering off her other meds as well. Since being transfusion-free, the weekly Neupogen injections have caused huge spikes in Haylee's ANC (as high as 8000+) within 48 hours followed by huge dips within less than a week (as low as 500) until the next injection. Haylee's overall recent ANC trend, however, has been increasing (along with HCT and PLT). Her ANC, in comparison to her HCT and PLT, continues to be the slowest to increase though. Why do you ask? We are aware of the risks to neupogen, but feel at this time, that the benefits outweigh the risks.

3. Yes, Haylee has been on prednisone daily since diagnosis with a brief break in April. When she was diagnosed back in Feb, her prednisone dose was around 180mg. Her oncologist has had her tapering off each month since then. Her current daily dose of 5mg has been in effect since June. Why did you ask this question?

I welcome your response - information can be life-saving.

[sandra]

Hi!

I don't understand why she was started on 180mg prednisone. This is a HUGE dose! When using prednisone to treat various conditions (not necessarily AA), any doctor would start at 1mg/kg, unless there is a specific rationale to up the dose. Even then, you'd want to start at lower doses and then increase as necessary.

According to the protocol used by Children's Hospital in Denver, glucosteroids are used to attenuate/ prevent serum sickness caused by ATG. Thus the patient receives twice a day methylprednisolone IV (Solumedrol) 1mg/kg for day 1 through 5, and then twice a day prednisone oral 1mg/kg for days 5 through 10, followed by taper till day 13.

N. Goldenberg and al. - Succesfsul treatment of SAA in Children Using Standardized IST with ATG and CsA - Pediatric Blood Cancer 2004; 43; p. 718

My son used a similar protocol from Boston Children's Hospital.

However, having been on such huge dose, it is normal to taper slowly (probably at 10mg/mo), and this discussion would be somehow moot.

About the Neupogen, I honestly believe is a very dangerous drug if used regularly long term as Haylee seems to be doing. I would be extremely reluctant to give to her unless her ANC drops below 200, and even then, only on a case by case basis (as needed per CBC). The following is a commentary that I posted on the Aplastic Central forum (please note that G-CSF is the same thing as Neupogen)

"There is quite a lot of controversy surrounding the use of G-CSF in AA patients. First to sound the alarm were the japanese researchers that found a strong statistical correlation between use of G and latter development to MDS.

Kojima et all - Blood, 2002, 100, p.786

The American researchers were initially skeptical, they pointed out that very large doses of G were administered in the japanese patient cohort (which was indeed true). However, the seeds of doubt were there...
So Young at NIH did his own studies (the following article is very technical, as is mainly lab research, but the title summons all up)

G-CSF preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor
Sloand, Young et all - Proceedings of the National Academy of Science of USA - 2006, 103, 39, p. 14483

Their findings were that the data "strongly suggest a mechanism by which G expands an existing monosomy 7 clone". They tried to downplay the risks of using G occasionally (as in healthy blood donors that sometimes receive shots after donating blood or surgery patients) but had to caution against long term use.

The Europeans in the meantime did a huge analysis of some 840 patients that received or not G.

Blood First Edition Paper, pre-published online November 16, 2006; DOI 10.1182/blood-2006-07-034272

They found a significant incidence of MDS/AML
in the patients that did take it (the doses were NOT as high as in the japanese study, what matter was length of use) Their findings "emphasise the necessity [..] to alert physicians that adding G-CSF to immunosupressive treatment is currently not standard treatment for SAA"

But, again, since her doctor plans to take her off Neupogen, this discussion is also somehow moot.

May I ask you what was her MCV (mean corpuscular volume) at diagnosis?

Sandra

[dkimmel]

What is considered long-term use for being considered at risk? I had daily IV G-CSF for many months.

[sandra]

Hi!

It is difficult to compare. In the japanese study, the minimum period was 3 mo to sometimes yars for non-responders, but they had daily injections with very high doses - 10 micrograms/kg/daily .

http://bloodjournal.hematologylibrar...ract/100/3/786

N. Young study is a lab study, it's done on cell cultures.

http://www.pnas.org/content/103/39/14483.full

In the European study, the dose was 5 micrograms/kg/daily for less than 6 mo.

http://bloodjournal.hematologylibrar...act/109/7/2794

Keep in mind, though, you fall into a different category. First, you had HD Cy, a treatment that ablates the marrow so severely, that I don't think you can survive without G. It is my opinion that even in the case of HD Cy, one should stop G as soon as medically feasible (ANC around 500). Second, later developing to PNH is not considered anymore an "evolution event" per se, as it is the case with evolution to MDS (triosomy 7 or 8). Rather, it is believed that the PNH was there all the time, but the clone was undetectable with available methods.

Sandra

[dkimmel]

You are correct, the PNH clone was present from the beginning. At time of dx w/SAA it was only 1%. It remained so until March of '08. It had expanded to 44%, and as of August it is 52%. Do you know of any studies/articles that hypothesize why it expands?
Also I had a BMB done in March. The results were a little worrisome for me. Though my doc is not concerned. It notes "dysplastic changes" "many small megakaryocytes" "blasts not increased above 3%" and "erythroid hyperplasia" and no chromosomal abnormalities. I know that PNH explains the erythroid hyperplasia. It's the dysplastic changes I'm concerned with. What are your thoughts ? I think you're much more educated on this stuff than I am

[Dan2008]

Hi!

I'll try to answer your questions

1. the PNH clone has a survival advantage vs normal cells, which means it has more protection against destruction by the autoimmune T-cells. There are studies which demonstrate that the autoimmune response against Stem Cells in AA is actually triggered by an abnormal clone (MDS or PNH). When the autoimmune response is full blown the patient presents with marrow failure and pancytopenia. After IST, the autoimmune response subsides and the original clone can expand. In this scenario, the normal marrow suffers collateral damage from an autoimmune response directed against an abnormal clone.

2. regarding your second question, the only concerning word there is dysplastic changes, but I can tell you that 10 Pathologists will look at the same smear and will come with 10 different reading when it comes to stuff like this, I think your doctor should talk to the Pathologist and see what he means by that. If you do it again, the dysplastic changes might be gone next time.


Hope this helps.


Dan

[dkimmel]

Hi, Thanks for the input. I would still like to know why/how the PNH clone remained dormant for 9 years, and now keeps progressing. My counts were normal for those 9 years. Seems like there was a trigger. I guess we'll never know. Just like most of us don't know where our AA comes from. Concerning the BMB. I hope that you are correct. I hope that when it is repeated it was a reader error. However it was done at Hopkins, but its not like they can't make mistakes right? I'm in no hurry to have it repeated anyway. I think I worry a bit too much.

[Dan2008]

No, I don't know what would determine a sudden expansion in a PNH clone. Things in this area don't always have a good explanation. You should probably try to find a hematologist with expertise in PNH, they might have more experience with the natural evolution of a PNH clone.

Dan