Just Some Information

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• June 3, 2005 at 5:07 pm #6605
  KP2112

  Member

  Hi everyone,

  I just wanted to share a bit about the medication that my father is taking. I have not heard it talked about in this forum but there is a lot being published about it currently. Basically the drug promotes apotosis (programmed cell death) for the bad cells and stimulates hematopoietic stem cell growth. Below is an abstract of an article I came across.

  Valproic Acid Stimulates Proliferation and Self-renewal of Hematopoietic Stem Cells
  (Cancer Research 65, 2537-2541, April 1, 2005)

  Histone deacetylase inhibitors have attracted considerable attention because of their ability to overcome the differentiation block in leukemic blasts, an effect achieved either alone or in combination with differentiating agents, such as all-trans retinoic acid. We have previously reported favorable effects of the potent histone deacetylase inhibitor valproic acid in combination with all-trans retinoic acid in patients with advanced acute myeloid leukemia leading to blast cell reduction and improvement of hemoglobin. These effects were accompanied by hypergranulocytosis most likely due to an enhancement of nonleukemic myelopoiesis and the suppression of malignant hematopoiesis rather than enforced differentiation of the leukemic cells. These data prompted us to investigate the effect of valproic acid on normal hematopoietic stem cells (HSC). Here we show that valproic acid increases both proliferation and self-renewal of HSC. It accelerates cell cycle progression of HSC accompanied by a down-regulation of p21cip-1/waf-1. Furthermore, valproic acid inhibits GSK3ß by phosphorylation on Ser9 accompanied by an activation of the Wnt signaling pathway as well as by an up-regulation of HoxB4, a target gene of Wnt signaling. Both are known to directly stimulate the proliferation of HSC and to expand the HSC pool. In summary, we here show that valproic acid, known to induce differentiation or apoptosis in leukemic blasts, stimulates the proliferation of normal HSC, an effect with a potential effect on its future role in the treatment of acute myeloid leukemia.

  Key Words: valproic acid • hematopoietic stem cells • histone deacetylase inhibitor • GSK3ß • Stem Cell Biology

  Kind Regards,
  Karen

  June 4, 2005 at 9:28 pm #6606
  shirlsgirl

  Member

  Thanks for the info Karen. Very interesting. How is your Dad responding to the Valproic Acid? Are there any side effects?

  Hope you are enjoying this beautiful weather.

  Jody

  June 7, 2005 at 4:17 pm #6607
  KP2112

  Member

  Jody,

  He counts seem to be maintaining better than they were. I would really like him to try Revilmid. Looking at your Mom’s chromosomal abnormalities they are similiar to my Dad’s. How is her medication working for her? Is she feeling good? Does she have many blasts?

  The weather is good, only thing it is too hot for my Dad to be out. He doesn’t feel great in this weather.

  Take care,
  Karen

  June 7, 2005 at 10:48 pm #6608
  shirlsgirl

  Member

  Hi Karen,

  My mom is at her hemo. doc. appointment as I write this and I am very anxious to hear how it went. She is now going every 3 weeks…her last CBC was normal..even platelets! As far as the way she feels…could be better, but I think she is finally getting used to to the drugs. She experiences nausea, fatigue, and swollen ankles but she still has an awesome appetite and she has some really good days. Mom’s last BMB was last October and blasts were normal (hoping they still are)
  Glad to hear your Dad’s counts are maintaining better. Hey, if your Dad’s chromosomes are similar to my mom’s wonder if Gleevec would be an option for him?

  Take care,

  Jody

  June 7, 2005 at 11:37 pm #6609
  shirlsgirl

  Member

  Well, just heard from Mom and her Doctor is still pleased. She has 3 low counts – rbc’s, hct, and MPV. Everything else holding steady. Hgb dropped to 119 but still low normal. Her next hemo. appointment is in a month. She’s very happy about that! And her next BMB is scheduled for October. She is now weening herself off of the cyclosporin…one pill every other day. Can’t complain…things look pretty good.

  Jody

  June 8, 2005 at 1:28 am #6610
  Terri

  Member

  Jody, It is always good to hear promising news.
  I am so happy for your Mom
  God Bless

  June 8, 2005 at 3:55 am #6611
  geebeebee

  Member

  Jody, that’s great to hear. Hope things just keep rolling forward.

  Take care,

  Greg

  June 8, 2005 at 4:36 am #6612
  kristyk

  Member

  Karen
  Such great news about your Dad. I noticed some weeks ago you posted question about decitibne. Is your Dad’s doc still suggesting he try this in combo with valproic acid? I’m fairly sure my Mom will be starting the drug( decitibine) within in the next few months and am starving to hear more about it. You know, I’m so new to this, but I am interested to learn that valproic acid is treatment potential for MDS. I’m very familiar with the drug in terms of its indication for psychiatric treatment as a mood stabilizer( I am assuming they are one in the same??) as that is what I do for a living…hmmm I will certainly be checking into this further..I will be hoping the best for your Dad…and would love to know what happened with the decitibine proposal you all had..did it go any further? I just keep learning so much from you all! And Greg..Is your mom being treated in KC? If so it would be the second person I’ve heard of in KC who had transplant that was over age 60…. If so I would love to know the facility name. Thanks. Hope for all. Kristy

  June 8, 2005 at 8:37 pm #6613
  KP2112

  Member

  Kristy,

  My Dad decided that he wanted to see how the valproic acid would work before trying it with something else.

  You are right in that VA is used as a mood stabilizer, for epilepsy and for migraines. In a study they did however, they found that it help with blood formation. It is not very well researched at this point but hopefully they will only discover more useful data.

  Thanks for everyone’s kind words.

  Jody I will look into the Gleevec thing as well. Glad to hear about your Mom.

  Hope all goes well with your Mom Kristy, keep us updated.

  Take care,
  Karen

  Karen

  June 9, 2005 at 2:29 am #6614
  geebeebee

  Member

  Hi Kristy,

  Yes, Mom is 65 and had a SCT in November. Hers was called a “midi” in that it was power-wise in-between a mini and a full one. In her most recent BMB, she had 100% donor cells and no evidence of any leukemic or MDS activity.

  That’s the good part. She has been recently beset with lots of problems, including graft-vs-host in the mouth, gut and liver, and had a recurrence of breast cancer that resulted in a mastectomy. All of this has taken a toll on her, and combined with her Parkinson’s, right now, she’s bed- and wheelchair-bound due to a lot of weakness.

  The clinic she went to was St. Luke’s in Kansas City. It has been a tremendous place for her — the doctors as well as nurses have been phenomenal. When Mom was first diagnosed, she did go to Barnes in St. Louis for a second opinion and thought they were very knowledgeable as well. St. Luke’s was one of the few in the country performing the midi so we were lucky with that.

  If you have any further questions, don’t hesitate to ask.

  Best of wishes,

  Greg

  June 9, 2005 at 1:16 pm #6615
  shirlsgirl

  Member

  Greg,

  I think about your mom all of the time. I was hoping she was feeling better…I’m sad to see that she’s wheelchair/bed bound. Do you know if the graft vs. host is temporary or is it a long term problem?

  Great news her BMB shows 100% donor cells. Hope your mom starts to feel better soon though.

  Take care,

  Jody

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