High dose cyclophosphamide at Hopkins?

[michelle_lapuz]

Has anyone tried this therapy for aplastic anemia? Would love to hear feedback both good and bad (but mostly good)....

Michelle

[DomesticDeeva]

Yes, I would like to know if anyone has also tried this drug treatment for treating Severe AA. And if so, what have been your specific results from such treatment? And how long have you had Severe AA?:confused:

[dkimmel]

I was treated with high-dose cytoxan at Hopkins at the age of 21 in '99. I achieved full remission. If you have any questions please feel free to contact me.

[ccartbmw]

Hi,
What elese was your treatment for your AA? I am getting ready for another round of ATG. And I would like to know so I can talk with my doctor about this medicine.Do you take it with cyclosporine? or is it instead of the cyclosporine.Or is it like cyclosporine?I am not responding to the cyclosporine any more, that is why they want to do another round of ATG.

Thanks ccartbmw

[DomesticDeeva]

Hello dkimmel,

Thank you for sharing. Have more questions:

I am unfamilar with cytoxan; is this a brand name for cyclophosphamide? How long did you have AA? Was it diagnosed as mild, moderate, severe or very severe? How long have you been in remission? How many months did it take until you saw positive results with cytoxan? What were the major side effects of cytoxan?

[dkimmel]

Sorry about the confusion, Cytoxan is the name brand for cyclophosphamide, I am a lazy typist...I was diagnosed with SAA in March "99. I lived in the DC metro area at the time. I went to both NIH and Hopkins before deciding on my treatment. My husband and I met both Dr. Young(NIH) and Dr. Brodsky(Hopkins). We chose to go with the treatment at Hopkins. Our reasons are kinda long so if you want to know just ask. The treatment at Hopkins was Cytoxan only, no cyclosporine. Followed up with daily doses of Neupogen. It was not an easy treatment, and my hair did fall out. Small price to pay for my quality of life since my recovery. I was treated in early May, and had shown my first sign of response on July 6 '99. I know because I saved the lab slip. It took about a year or so for everything to really come up. But all three cell lines made a coplete recovery. Cytoxan was my first line of treatment, I did not have ATG prior. I have been in remission for about 9 years now. Although recently I have encountered a little "hiccup". My counts dropped quite low in Dec. "07 and have remained low. I have had a bone marrow biopsy at Hopkins, I am not relapsing and do not appear to have any other issues. It has been explained to me that certain virus' may suppress my immune system more. My doctor believes that they will come back up, it will just take some time. In 9 years this is the first real issue I've had with reguard to SAA and its treatment. There are no guarantees with any treatment, but my experience has been a good one. I strongly suggest consulting with Dr. Brodsky before you proceed with any treatment. He is a GREAT doctor who will give you all the time you need during a phone consult, or in person. I am not sure if he would be the person who treats pediatric patients but he would be happy to point you in the right direction. Please feel free to send me an e-mail or private message if you have any questions or would like Hopkins contact info.

[Marlene]

My husband did High Dose Cytoxan in June of 2002. It was his first line of treatment. He is in a partial, stable remission. His counts are still improving at very slow pace. He's been transfusion free since April 2004.

I too think it's best you consult with Dr. Brodsky directly. He will spend as much time as you need to understand the protocol and he can give you the latest statisitics on response rates, etc....

High Dose Cytoxan appears to work best when it is the first treatment given for SAA. Dr. Brodsky can give the breakdown of response rates by SAA, VSSA and those who had prior ATG treatment.

[DomesticDeeva]

:confused:
Our current doctor stated that sterilization in females is a common long term side effect of cytoxan. Is this true? Are there any females out there who have had VSAA and took cytoxan and are willing to share all side effects both short term and long term? Also, we are located in Spokane, WA - does anyone know of any AA specialists in the Pacific Northwest?
Thank you.

[Neil Cuadra]

Also, we are located in Spokane, WA - does anyone know of any AA specialists in the Pacific Northwest?
You can contact the Seattle Cancer Care Alliance (http://www.seattlecca.org) (SCCA). Their alliance includes the Fred Hutchinson Cancer Research Center (http://www.fhcrc.org) and the Children's Hospital & Regional Medical Center (http://www.seattlechildrens.org).

See also the SCCA's aplastic anemia (http://seattlecca.org/patientsandfamilies/adultCare/clinicalProgs/Aplastic/Treatment.htm) page, which has "Find a Doctor" and "Make an Appointment" links.

[michelle_lapuz]

High dose cyclophosphamide definitely impacts fertility in women - stay away from it if you or your daughter consider having children in the future....if I do decide to undergo this treatment, I will definitely have some eggs frozen - I never kept the cord blood with my two children and if anything happens to them in the future I would like the ability to have another matched sibling in order to help them just in case.....I hope your daughter pulls through this without too much intervention (sometimes these things just spontaneously improve - at least that is my hope)....

Michelle

[sandra]

Also, we are located in Spokane, WA - does anyone know of any AA specialists in the Pacific Northwest?

Dr. Shimamura recently moved from Children's Boston to Children's Hospital in Seattle. She is an AA specialist and she is a great doctor, I would trust her completely.

Sandra

[Neil Cuadra]

Dr. Shimamura recently moved from Children's Boston to Children's Hospital in Seattle. She is an AA specialist and she is a great doctor, I would trust her completely.
Here is Dr. Akiko Shimamura's information page (http://www.seattlechildrens.org/our_services/find_physician/detail.aspx?id=258053) at the Children's Hospital & Regional Medical Center site.

[Marlene]

I highly reccommend you contact Dr.Brodsky directly to get your answer. There is a risk of infertility with High Dose Cytoxan as well as with BMTs. Dr. Brodsky can give you the latest statisitic and the names of other patients for you talk to as well. It can also depend on the age of the patient. Example....a women in her perimenapausal years may be at higher risk for the infertility side effect than a child. I know that low-dose, long term cytoxan has greater chance of causing infertility than the 4 day High Dose.

But don't quote me......If you want more info on High Dose Cytoxan, then it is so important to talk to the expert on it. It is a clinical trial and they are still collecting data on it so outcomes, long term side effect, etc is fluid. Dr. Brodsky is very upfront about the risk, outcome and side effects of the protocol.

[Gary]

Although my mom did not go through this therapy, I do remember looking into it.

I posted a pretty long entry here (http://gkleiban.blogspot.com).

From what I can gather, unless there is more recent literature that I am unaware of, it appears there is insufficient data to determine whether immunosuppression via cyclophosphomide is indeed a treatment modality to rival the standard ALG/ATG + cyclosporin.

But of course, the best thing to do is get in contact with an expert.

dkimmel,
Could you tell us why cytoxan was chosen in your case?

[dkimmel]

I am having a difficult time trying to answer this question. It has been many years since I have had to think about it. I guess I would start by saying that I CHOSE to recieve high dose cytoxan, it was not chosen for me. When I was first diagnosed with SAA my local hematologist sent me to NIH because he heard there was a different treatment available. The treatment was high dose cytoxan. They were doing a study of ATG/cyclo vs. HD CY. After spending many hours questioning Dr. Young about the HD CY, my husband and I were very interested in learning more about HD CY. We were referred to Dr. Brodsky at Johns Hopkins, where HD CY was done exclusively. After spending many more hours questioning Dr. Brodsky about HD CY we felt convinced it was the better treatment for me. I can only speak of my own experience, so please consult educated physicians if you have questions. We felt that the risk of relapse was much lower with HD CY. We felt that the risk of second clonal diseases was much lower with HD CY. We also felt thet the quality of life that could be attained far exceeded that with ATG/ cyclo. As I understood it at the time, Atg/cyclo was also given with long term doses of prednisone. Prednisone comes with many debilitating effects. As a 21 year old, just married, mother of one, I didn't want all the side effects of prednisone, if I had a choice. Also, I understood that even if I responded to the ATG/cyclo, my blood counts would probably never be at a normal level. I didn't want to live a "half-life" (as I called it). With HD CY, I had understood at that time, that the majority of responders had achieved full remission. Even though there were not alot of people who had undergone this treatment, they seemed to have better results. I felt I had a better chance of full remission with the HD CY. I should mention that HD CY was my first and only treatment ever. Within months, I no longer required transfusions. Within the year almost all counts were normal. Two years after treatment, I had my other daughter. Almost ten years with no health issues. I have no regrets about my choice. For me, I whole-heartedly feel that HD CY gave me my life back. I am not advocating that everyone run out and choose HD CY. As I said, it was a personal choice, that apparently was the right choice for me. That doesn't mean it is the right choice for everyone. It is a far more immunosuppressive treatment, that does come with severe risks.
Sorry this post was so long, if you can believe it, I even left alot out : )

[Gary]

Thanks for letting us in on your treatment and thought process!
Very, very good post.

Trying something outside the normal protocol was extremely brave of you, especially 10 years ago when data was even more scarce.
You also had arguably the leading authority on the treatment. I know how encouraging it could be when you have an expert that thoroughly explains things and happily answers all your questions.

I think it's important to continue to emphasize that you need an experienced physician, especially if it is a treatment that's not the standard.

I could imagine you still left a lot out ... I know I can go on forever about my mom's case :-).

[Lynn del]

Sorry about the confusion, Cytoxan is the name brand for cyclophosphamide, I am a lazy typist...I was diagnosed with SAA in March "99. I lived in the DC metro area at the time. I went to both NIH and Hopkins before deciding on my treatment. My husband and I met both Dr. Young(NIH) and Dr. Brodsky(Hopkins). We chose to go with the treatment at Hopkins. Our reasons are kinda long so if you want to know just ask. The treatment at Hopkins was Cytoxan only, no cyclosporine. Followed up with daily doses of Neupogen. It was not an easy treatment, and my hair did fall out. Small price to pay for my quality of life since my recovery. I was treated in early May, and had shown my first sign of response on July 6 '99. I know because I saved the lab slip. It took about a year or so for everything to really come up. But all three cell lines made a coplete recovery. Cytoxan was my first line of treatment, I did not have ATG prior. I have been in remission for about 9 years now. Although recently I have encountered a little "hiccup". My counts dropped quite low in Dec. "07 and have remained low. I have had a bone marrow biopsy at Hopkins, I am not relapsing and do not appear to have any other issues. It has been explained to me that certain virus' may suppress my immune system more. My doctor believes that they will come back up, it will just take some time. In 9 years this is the first real issue I've had with reguard to SAA and its treatment. There are no guarantees with any treatment, but my experience has been a good one. I strongly suggest consulting with Dr. Brodsky before you proceed with any treatment. He is a GREAT doctor who will give you all the time you need during a phone consult, or in person. I am not sure if he would be the person who treats pediatric patients but he would be happy to point you in the right direction. Please feel free to send me an e-mail or private message if you have any questions or would like Hopkins contact info.

Hi, I am really interested in getting in touch with Dr. Brodsky. My e-mail is del1134@yahoo.com, I have had AA since 1998 and had 1 ATG in 1998, since, I have had only blood transfusions which are getting closer and closer.
Thank s for any help you can provide. Lynn

[Ruth Cuadra]

Dr. Robert Brodsky is Director of Hematology at the Sidney Kimmel Cancer Center at Johns Hopkins University. For appointments, call (410) 955-8964. You can read some details of his background here:

http://www.hopkinskimmelcancercenter.org/experts/doctor.cfm?DoctorID=26

Regards,
Ruth

[dkimmel]

I know this is an old topic but I have new news to share. I have been reluctant to post this, but mostly because I am in denial. Because I have shared my experience with HD CY this update is pertinent. I had mentioned in my post that my counts dropped significantly in Dec. of '07. As it turns out, I have recently been diagnosed with PNH. I believe I am the only one who has had HD CY to get PNH.

[Ruth Cuadra]

Hi, dkimmel.

This must be a very difficult situation for you. After having had a good response for so many years, I understand that you are facing the return of the monster that lurks in the back of our minds as survivors. Your post, though difficult to share, was an important contribution to this forum as it shows the need for vigilance about our health even when the disease seems to have been eradicated.

What treatments are being suggested for your PNH?

Regards,
Ruth

[dkimmel]

Hi Ruth,

What can I say, 9 years of great health, I'll take it. My PNH as of now, is considered moderate. My only symptom is fatigue. For now, I'm okay without treatment. However it is thought to be progressing, and I will have my clone size checked again in August. If it continues to expand, Soliris is the recommended treatment. I am in no hurry to start this drug. It is unbelievably expensive. All things considered , it could be worse.

[bchenaille]

Hi dkimmel:

I know it has been a long time since your post about discovering your PNH after undergoing the Cytoxan at Hopkins. My daughter had her Cytoxan at Hopkins back in November 2008 and her counts are doing great. When I read about your PNH, it was a kick in the gut, but I am sure it was a shock to you. I am so sorry to hear that you have to deal with yet another situation after having gone through AA.

How are you doing now? Do you have any advice for me as a dad for my daughter? I hope to hear from you soon.

Bill Chenaille
bchenaille@comcast.net

[dkimmel]

Hi Bill, I'm very sorry to hear about your daughter's diagnosis. But it sounds like she is well on her to recovery. I have three daughters of my own. To say that I would be devastated is a gross understatement. I simply cannot imagine. I can certainly understand your concerns for her future health. I can start by saying that I was told, by my doctor at Hopkins, currently I am the only patient who recieved HDCY that has a PNH clone the has expanded. What I mean by that is, apparently at time of diagnosis with SAA, I also had a PNH clone of about 1%. I was unaware of that at the time. (Your daughter was tested for PNH as well, I'm sure of it. If you do not already know the results, I would ask.) Many AA patients harbor a small PNH clone. It is actually thought to be beneficial. It is believed to provide a better outcome from immuno-suppressive therapy, for reasons not exactly clear yet. I could go into the thought behind it, but my posts are already too wordy :) So, as I understand it, for these patients who have small PNH clones, they tend to stay small indefinately. HDCY does not erradicate them, only a BMT can. But they stay small, for reasons not understood. So, again for reasons not understood (there's alot we don't understand, huh) my clone decided to expand from about 1% to now about 50%. But remember, as I understand it, currently I am the only one. So that means, all other patients who have had HDCY, have not gone on to get clinical PNH. And many of them I'm sure had some kind of detectable PNH clone at time of diagnosis. So the odds are greatly in your daughters favor to remain disease free. Even if you find that she has a small PNH clone, it will most likely remain small.
As for me, you asked how I am doing. I am doing fantastic. I recently had my clone size checked. It is stable. I mentioned that a year ago all of my counts fell dramatically. They are all on a consistent rise, some even within normal levels. I continue to be medication free. I continue to exercise and live a life pretty much unaffected. I mean I have to get my blood checked every couple of months. That is usually stressful. There is always the worry that it will progress out of nowhere again. But these are things out of my control. So I just try to appreciate the now, and not worry too much about the later.
I would ask do you have any advice for me? It's much easier to be the patient I think ,than to be the parent of a patient. I sincerely mean that. I hope this helped to calm some of your concerns, impossible I know. Please feel free to ask any more questions.

[bchenaille]

Hey dkimmel:

I am so sorry for not seeing your response to my initial post. I am such an email person and keep close contact with many AA patients directly through that. If you are up for it, I posted my email in an earlier post.

As you know, the best comfort is always given by those who have blazed the trails before you so I thank you for the encouraging words. I truly hope that your PNH can remain controlled and you don't have to move on to a BMT. But if you do, you are in good hands at Hopkins. I was recently communicating with Dr. Brodsky and he mentioned they were having tremendous success controlling GVH using cytoxan. As time passes, the success of BMT's just keeps getting better & better.

The only advice I have is looking into reducing your toxins and increasing your anti-oxidents. I know many of these steps may seem a bit theoretical, but even if there is a "slight" chance we could prevent Kathryn's body from developing a clonal disorder, I am all for it.

1. Eating lots of blueberries. (anti-oxidents)
2. V8 V-fusion with Acai & Blueberries
http://www.v8juice.com/Products.aspx
3. Tons of Green veggies: Broccoli, Spinach, Brussel Sprouts, etc...
4. Walnuts - Omega 3
5. Flax Seeds & flax seed oil - Omega 3
http://www.usatoday.com/news/health/diet/2002-05-01-omega3.htm
6. Nordic Natural's Omega-3 Fish suppliments.
http://www.nordicnaturals.com/en/General_Public/Product_Line/66/
7. AVOID SODIUM NITRITES IN MEATS LIKE THE PLAGUE.
http://www.grocerywarning.com/
8. Avoid Hi-Fructose Corn Syrup & Corn Syrup
9. Using safer sun screen & bug repellent.
http://products.mercola.com/summer-survival-kit/


Sodium Nitrite is a know carcinogen and has been in deli meats (hot dogs, sausages & MANY deli meats) for years. The Univ. of Hawaii conducted a recent study linking SN to a 67% higher chance of getting Leukemia when consuming a monthly amount of sodium nitrite equivalent to 12 hot dogs. So when you are eating that turkey sandwich from the deli and thinking you are eating healthy, check to see if it has SN. I was shocked to learn how well known this carcinogen is and yet we still pack it in to so many foods.

I do pray every day that Kathryn's ordeal is behind her. Yet, there is that demon that lurks in the shadows that we will never be sure if/when he will jump out at us. This is where our faith comes in to play.

Please let us know if you have found out any specifics as well. Besides being a great place to meet others in your same situation, this forum is also an incredible place to share information.

Hope to talk to you soon. I will check this forum more often.

Bill Chenaille
bchenaille@comcast.net

[flyguy]

Has anyone tried this therapy for aplastic anemia? Would love to hear feedback both good and bad (but mostly good)....

Michelle

Hi Michelle,
I have mAA and went to J H in June for a consultation with Dr Robert Brodsky who published the study on high dose cytoxin for sAA. He doesn't recommend the treatment unless you have severe AA. I was disappointed but it was worth the try. He is down on most vitamines and overmedicating until lifestyle or bad blood numbers dictate going toward conventional treatment for mAA, at least that's what was the outcome of my visit. He is a very nice man and we were treated very well for the consultation visit.
Good luck
Fly guy

[destiny09]

We were advised to stay away from this treatment from our doctors, due to the fact that the national instutue of health shut down their study due to a high death rate.... We to have a 12year old that is diagnosed from severe aplastic anemia. She didn't respond to ATG she is still 95% production lost at her cellural level. She is recieving one red cell and two platetlet tranfusions a week. She has had over 112 transfusions since may. The childrens hospital wants to do an emergency bone marrow transplant on her, we are currently waiting for the bone marrow center to find a match as two donars haven't panned out.

[flyguy]

We were advised to stay away from this treatment from our doctors, due to the fact that the national instutue of health shut down their study due to a high death rate.... We to have a 12year old that is diagnosed from severe aplastic anemia. She didn't respond to ATG she is still 95% production lost at her cellural level. She is recieving one red cell and two platetlet tranfusions a week. She has had over 112 transfusions since may. The childrens hospital wants to do an emergency bone marrow transplant on her, we are currently waiting for the bone marrow center to find a match as two donars haven't panned out.

Hi Destiny,
I'm so sorry about your daughter. I certainly hope she starts producing more cells via some treatment. She certainly needs some relief to those transfusions every week. When I went to Johns Hopkins I was not transfusion dependent and was diagnosed with mAA. I went off cyclosporin and within 3 months was not producing many cells and went toward sAA when my platelets were 4,000 or so. I went thru ATG locally and spent 12 days in the hospital and still have side effects from the treatment. I now require 2 units of platelets weekly but about 3-4 weeks between packed red blood cells. I won't know if the ATG helped for 4 or 6 months, I'm told. I am 68 years old so my response is a lot different from your daughter's, I would think. Please let us know what is happening. I hope a donor will work out. I know you life and hers is in tatters with the waiting, but I really think something will turn around for you.
Much love and support,
Flyguy

[Marlene]

Destiny,

The NIH HiCy study used a different protocol and did not have the anti-fungal meds that are available today. The advice from your doctors is out of date and misleading. If you are interested, then you need to contact Hopkins directly to get the data on outcomes for all populations. There are different response rates depending on whether or not you've had ATG before doing HiCy. Having HiCy as the first line of treatment has a better response rate than if you had ATG first. BTW, NIH funded the High Dose Cytoxan clinical trial at Hopkins so they still thought it had merit even though their trail failed.

At the time when John went through HiCy in 2002, no one with SAA had died from the treatment.

I hope they find a donor for your daughter quickly.

Take care,
Marlene

[bchenaille]

Hey Destiny:

I continue to pray for your daughter's health. I can't imagine how you must feel having her endure this prolonged neutropenic state.

My daughter Kathryn went through the HyCy treatments. The one thing that I would really encourage is to reconsider your options. Everyone agrees that the most dangerous situation is prolonged neutropenia. The longer the wait to find a MUD donor, the more dangerous her situation.

As for the recommendation NOT to look into the Hopkins protocol using cyclophosphamide, I am a bit dismayed that the medical community still sticks to the merits of the NIH study which wrongly added cyclosporin. This clearly caused toxicity in the patients and the results were skewed. Dr. Brodsky just published the results from the Hopkins clinical trial and the figures are very exciting. You can read about it at: http://bloodjournal.hematologylibrary.org/cgi/content/short/blood-2009-06-225375v1

What were the dangers for Kathryn? Yep, catching a virus, fungus, or other germ during her recovery phase. Did she make it? Yep, just like everyone else I know who has gone through this treatment. She is back to living a normal life once again. Praise God!

Unless I am missing something very important, here's the weighted scales:
1. Cytoxan @ Hopkins: 4 days of hi-dose chemo, antibiotics & GCSF. After a slightly longer neutropenic state, the body begins to regrow its own hematopoietic stem cells. No radiation, no GVHD, no steroids, no other drugs.
2. MUD BMT: 4 days of hi-dose chemo, full body radiation, foreign marrow, GVHD, steroids, et all.

With all the possible side effects of the MUD BMT, it may be worth exploring this route that could be started now and get her body recovering sooner rather than later. Nothing is foolproof with this dreaded autoimmune disease. But having gone through it, I am so incredibly thankful that others who had blazed the Cytoxan trail had encouraged me and our family.

Baltimore is also home to the Ravens. They come to the local Ronald McDonald House to give out signed footballs to the kids. If for no other reason, maybe you would choose Hopkins to get her a football? :-) (I know . . . dumb joke, sorry!)

bchenaille@comcast.net