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#1
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Crowdsourcing my next therapy -- Get your 2 cents in!
Hi All!
I need your help. I heard back from Dr. Matt Olnes, the Principal Investigator on the NIH Campath Trial in which I have been participating, to whom I had sent my latest bone marrow biopsy reports. The meat of his response was: "The decrease in trisomy 8 may be an effect of immune suppression. However, your continued lack of erythroid response remains a lingering problem, and given that it’s been close to a year since we treated you, it is unlikely that we’ll see a response this late. I think it is a good time to consider other therapies at this point vs continuing with supportive care. Revlimid would be a reasonable drug to try. The down sides are the risk of lowering your platelet and/or WBC while on it (it usually rebounds after stopping it), and a low risk of blood clots." So, it's time for me to go shopping for my next therapy, and I want your help! I'm going to be collecting as much info as I can on several options -- some of which I don't even know about yet. I'm a pretty good Googler, of course, and can go find information on my own. But why should I let this incredible pool of talent called "marrowforums" go to waste? In the newspaper biz, something called "crowdsourcing" is all the rage. That's when you get streams of info coming in from regular citizens on the scene or in the battle -- like all those tweets and YouTubes coming in from Cairo during the uprising. So I want to use my pals on marrowforums to "crowdsource" my research on my next treatment. Here's my thinking so far: What we aren't going to do -- Transplant. Not as long as I'm INT-1 with no appreciable increase in blasts and no really nasty chromosomal abnormalities, like Monosomy 7. So transplant is out for now. Hypomethylating agents (Vidaza & Dacogen). These have proven themselves for high-risk folks but not low-risk folks. Better to save them for later. So these are out of consideration, too. What we are considering -- Revlimid. I'm not 5q minus, but there are several trials underway with Revlimid for non 5q minus, low risk folks -- particularly those with primarily RBC issues. Response rates, as I understand it, are pretty good. My platelets, at 85-95, should be high enough that the well-known negative impact of Revlimid on platelets shouldn't put me in the danger zone. Ezatiostat. This new drug, by Telik, has been trialed some and shown pretty good response rates, with transfusion independence in 35% and transfusion reduction in 61% of MDS patients in a phase 1 trial of an oral formulation. Interestingly, a Phase 1-2a trial of an injectable version showed poorer results. HDAC Inhibitors. Valproic acid and all its cousins are another option, though most of the trials for these seem to combine them with Vidaza or Dacogen in higher-risk patients. I'm not inclined to got that route, but I am interested in their use in lower-risk patients. What else? You may have run across other drugs that would be appropriate. Let me hear about them. If you have access to research on any of these, or firsthand experience, I'd love to hear about it. Both my docs are going to lean toward Revlimid, and I may lean that way, too. But I want to leave no stone unturned. And I'd be truly grateful for your help in turning over the rocks I know about and finding new rocks to turn over. I'll be sharing summaries of whatever I learn with the marrowforums community, so we all can benefit. Thanks in advance for your data, experiences, and thoughts. Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#2
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Greg,
You are so much more knowledgeable than most of us about MDS that I wouldn't even begin to try to advise you. I'm sure you'll research and come up with the best course of action to pursue next. I pretty much have to let the doctors advise me, and then research it to death after I get home. Good luck with whatever you decide. Linda
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Linda, Al's wife, 75; dx MDS 5/2010; Vidaza 6/2010; ARRY614 & Sapacitabine clinical trials at Emory, no results, stopped 12/2011. Had BMB at NIH on 6/5/12, blasts 10-15% so he's not eligible for trial there. :eek Promacta trial, Tampa, blasts 25-30% 8/17/12 AML, trying Dacogen now and praying. |
#3
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Treatment Change
Hi Gregg;
I've had a little experience with Revlimid and will look at some of the connections I had on line. I know in Canada Rev-Aid has to administer the dispensation of Revlimid. The are at: http://www.revaid.ca/revaid/Default....ookieSupport=1 Yes, the platelets can be reduced for a period of time and then stabilize. Our doctor was going to go ahead even though my wife's platelets were at 5-10. This decision was because with the 5g minus it seem the best and only option. With MDS 5gminus the tests have shown a good response from Revlimid. I think it's definately worth looking further for Revlimid. Your platelet level should withstand the Revlimid hit on the platelets. I've read somewhere deep in the online info that a platelet level of 5 with MDS can be a maintenance level with no bleeding. Is that hard to believe? My wife has been at 5 many times for weeks at a time. At the same time the bleeding issue can happen at different levels for different people. Revaid indicates that Revlimid should be stopped when the level gets down to 50 and started again when it gets back up. As you can see, a lot of conflicting info. I gave my concern in regards to the platelets to my doctor who then decided to do another bone marrow biopsy. With the results of increasing blasts she decided to go to Vidazza instead saying that Revlimid wouldn't touch what my wife had. The Vidazza did very little but then it was done for only three months. Was my doctors response a due dilligence response to my concern? I don't know. Revlimid cost to us would be $10,000 a month with several plans covering everything except $1500 in a year. The only question is if the Revlimid would covered if the 5gminus was not there. Sorry for the rambling. Vidazza was administered in hospital as injections and was fully covered by the Province of Ontario. It's not a clear and friendly situation with these diseases and doctors who often do not know because research on MDS and the sub-types is still limited compared to other diseases.
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Wife 63, June 2010 MDS (refr anemia - excess blasts type-2) PLTs 11,000/μl with giant forms 2 TF/wk. Hgb kept at 80g/l with 1TF per 2 weeks. 9% blasts 2 cytogenic abnormalities del(5)(q22q35) + inv(20)(p11.23q11.21) 3 cycles Vidaza no effect. June 2011 to AML WBC to 67 blasts and Aur rods in blood. |
#4
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Hey Freedom!
Thanks for the info. Down here south of the border, as well, Revlimid hasn't been approved for us non-5q minus folks. So, if I decide on Revlimid, I'll either have to sweet-talk my insurance company or find a clinical trial. I might go the latter route in any case, just to help build up the dataset needed to see whether it's worthwhile for non-5q- folks. I appreciate the info on platelet impacts. I've picked up from folks on marrowforums that the reaction to very low platelets can be highly variable person to person. Take care! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#5
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Hey Linda!
Thanks for the kind words, but I know a lot of folks on marrowforums have these great piles of cool research stored up on their hard drives, ripe for the picking. That's why I'm taking the lazy man's approach to my research. Hope you and Al are doing well; good luck on the trial! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#6
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Revlimid was the first choice next step offered by Bruce's hematologist (not an MDS Specialist), though Bruce does not the 5q del.
After Aranesp failed this year, the Hem consulted with Dr. Paquette, who also mentioned the clinical trials of Revlimid. So, it seems like Revlimid is very popular choice right now. One bit of good news is Revlimid has been around long enough that there is reasonably good data about dosages and side effects.
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Catherine, wife of Bruce age 75; diagnosed 6/10/11 with macrocytic anemia, neutropenia and mild thrombocytopenia; BMB suggesting emerging MDS. Copper deficient. Currently receiving procrit and neuopogen injections weekly, B12 dermal cream and injections, Transfusions ~ 5 weeks. |
#7
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Low risk MDS
Hi Greg,
Like you I was dx with MDS Interm-1, all counts low and tx dependent from dx 2006. My EPO was more than 800 so I was not treated with EPO drugs. I felt OK and was satisfied with supportive treatment until I needed tx every week during the spring 2010. Then I accepted Thalidomide with good results. I asked my dr if I could continue with Prednisone since Thalidomide (and Revlimid) increase counts in different ways. If you choose Revlimid remember that they now give lower doses for less toxicity - they can get positive result with 5mg every other day and the drug should be combined with Prednisone or a similar drug. You have perhaps already seen the presentation of Dr Alan List from Edinburgh 2011. He is reporting about the new drugs for MDS. Perhaps you will find one of them interesting? http://www.multiwebcast.com/mds/2011...and.q%26a.html Kind regards Birgitta-A 72 yo, Thalidomide since June 2011. Last tx Sept 2010. Latest counts HGB 13,2, WBCs 5.0 and platelets 95. |
#8
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2 cents worth
Hi Greg,
First of all, thanks so much for all your entertaining and informative posts. You have a great way of explaining complicated things in simple, understandable ways. I have to agree with the others, I think if I was in your situation that I would go with the Revlimid if the every other week transfusion schedule is getting too onerous. Of course, you are lucky that you appear to have plenty of time to make this decision since you can always fall back on transfusion. I'm sure that you already know the reported anemia response rates to Revlimid (in non 5q patients) as being about 26% for transfusion independence and about another 17% for a greater than 50% reduction in transfusion for a total response rate of 43%. I've been intrigued by Birgitta's good response to low dose Thalidomide but you don't hear many of the experts recommending that here in the U.S. I know Revlimid is the supposed next-generation drug but is it really any better than low dose Thalidomide? I'm not sure how the costs compare either. You might ask Dr. Olnes about this. I wish that I had the option of Revlimid or Thalidomide instead of Vidaza but apparently my platelets are too low to risk them and my Hb has fortunately stayed in the 9 range. By the way, are you on any other medications that could be affecting your anemia or are there any signs of hemolysis or blood loss lowering your counts? Here's hoping that your transfusion interval will lengthen again so you can put off this decision. Good Luck tytd
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possible low to int-1 MDS with predominant thrombocytopenia, mild anemia, dx 7/08, in watch and wait mode |
#9
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Quote:
My local doc uses Revlimid for his multiple myeloma folks and says it is pretty well tolerated. My platelets and neutrophils are high enough that neither he more Dr. Olnes feel that the very common neutropenia or thrombocytopenia would be an insurmountable problem. Thanks much! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#10
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Quote:
Thanks for the tip on the List presentation. I haven't yet viewed any of the Edinburgh presentations but have them bookmarked for viewing. I'll try to watch List first. I'm not sure I know the answer to the question that Tytd raises, which is why thalidomide is less used that Revlimid in the US. My local doctor felt that thalidomide has more significant side effects, but I seem to recall reading the reverse opinion elsewhere. And I'm sure at least some of the adverse reactions are likely dose-related. Thanks much! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#11
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Quote:
I will ask Dr. Olnes about this. If thalidomide is cheaper, one might wonder whether the profit motive is at play. I fully expect, since Revlimid is not approved yet for non-5q, that I will be doing a clinical trial, even if that's my next choice. I think I'll do some searching on Thalidomide for MDS in clinical trials.gov. Thanks much! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#12
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Hi Greg again,
Something just popped into my head which is probably way stupid but I thought I'd bring it up anyway. When I asked one of my consultants last year about the possibility of trying Campath, he kinda shrugged it off, commenting that it might activate CMV. In reviewing your history, I wondered if you might have had an activation of CMV in April when you had the pleurisy/pneumonitis. Could a low grade activation of CMV be depressing your RBCs and might that get better with time? You probably had your CMV status checked before Campath?? Tytd
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possible low to int-1 MDS with predominant thrombocytopenia, mild anemia, dx 7/08, in watch and wait mode |
#13
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Thalidomide and Revlimid
Hi Greg,
You know Thalidomide is an old drug invented about 55 years ago and 50 mg costs about $7.5. Revlimid is new and 5 mg costs about $200. I have read many studies about Thalidomide and found that “less is more”. In one study they tried to give the poor patients 1000mg/day and only 8% responded. The best result – 59% responders - was reported from this study. The responding patients received 200mg/day at least 8 weeks. http://www.ncbi.nlm.nih.gov/pubmed/16351636 The results should probably have been better if they had given the patients lower doses of Thalidomide combined with Prednisone (or a similar drug) as they do with patients with Myelofibrosis and Myeloma. As far as I understand there are no ongoing studies on Thalidomide but many on Revlimid. Thalidomide can give neuropathy, fatigue and constirpation. If you take 25 mg/day there is hardly any risk of neuropathy - I take 29 mg/day. Revlimid can give low counts initially. Kind regards Birgitta-A |
#14
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revlimid
I have been on 5mg of Revlimid for over a year now. I am also not 5q like you. My hbg is averaging around 10. Without it I drop to the 8's. Yes your platlets and your whites will drop. 2 months ago I had to add Neupogen to the mix to boost my neutrophils to prevent some annoying viruses. I don;t know if this helps or not but so far it is working for me.
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#15
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Greg,
Hard to say with the Revlimid option. Many people experience short-term reductions in platelets/RBC only to see them increase and get back into the normal range after a couple of months. I did see a recent study that tied transfusion independence to initial starting dose, which is 10mg/day as opposed to the 5mg dosage, although many people do respond to the lower dose. A lot of folks go through at least a temporary dose reduction, but this does not seem to alter the overall response. Although i normally swim upstream, i think that I am falling in-line with the crowd here and saying that Revlimid seems like a logical choice. The very bright spot is that most responses are within 90 days, so you would not be wasting a lot of time on the drug. For some reason though, I would want to know more about why Thalidomide is off the table. It tends to do well with mild fibrosis and helps increase RBC in a good number of patients when the dosage is not very high, as Birgitta mentioned earlier. 100-200mg/day seems to be the sweet spot. I am pretty sure the answers are yes, but have you already been tested for the Jak2 V617f mutation and for PDGFRB? For the latter, Gleevec has been used successfully - for the former, I haven't seen a whole lot of research, but a Jak inhibitor might be interesting. this may have been 4c worth of feedback though. Good luck finding the answer!
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MDS RCMD w/grade 2-3 fibrosis. Allo-MUD Feb 26, 2014. Relapsed August 2014. Free and clear of MDS since November 2014 after treatment with Vidaza and Rituxan. Experiencing autoimmune attack on CNS thought to be GVHD, some gut, skin and ocular cGVHD. Neuropathy over 80% of body. |
#16
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Thalidomide
Hi Dan,
Many patients get neuropathy when they take Thalidomide. That adverse effect is dose related so with very low doses neuropathy could be avoided. Kind regards Birgitta-A |
#17
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Quote:
Excellent question! Campath is evidently noted for CMV reactivation (my transplant doc called it "a horrible drug" for that reason), and can evidently reactivate Epstein Barr Virus as well. The NIH trial's follow-ups include regular screenings for both, and mine have been negative. Dr. Olnes told me that they have seen CMV counts rise a bit in some Campath patients, but never to the point that they were clinically expressed. That short-lived pleurisy or pneumonia I had was an odd case. It lasted about two days (only a half-day of pain) and then just disappeared. Very strange. Take Care! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#18
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Quote:
Thanks for that information. I asked Dr. ones about thalidomide, and he replied that there aren't many studies on using it for MDS and that it seems to have a higher risk of blood clots where it is used, for example, in myeloma patients. Not to be a cynic, but my guess is there are fewer studies and less data in part because it is an old, less expensive drug, with fewer pharmaceutical company dollars available to fund studies. Thanks! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#19
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Quote:
Thanks for that firsthand account. Did they start you on 5mg from the git-go? It's good to hear from a fellow non-5q who's using the drug to good effect. I could stand a Hgb count of 10 or so right now. It's been a couple of busy days at work and my behind is dragging! Take care! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#20
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Quote:
Four cents, ten cents, a dollar -- I'll take all the feedback I can get. I have not been tested for any of that alphabet soup, unless someone did it while I wasn't looking (You can never tell, there's a section of that NIH building that has a 13th floor. Who knows what goes on up there!). But I will definitely look into it. Have you been tested for those? Do you ever wonder why they make up these odd names for genes? Seems like they could have just given them all numbers, like the Dewey Decimal System, and made things a lot less complicated. It's like the typing system for blood antibodies: Big-C, little-e, Jfk, Jfg, it's like bad coffee and good presidents all rolled into one. Time to go look up some alphabet soup and nag my doc to have me tested! Thanks much! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
#21
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Greg, you do get me laughing, it's a wonderful gift you have.
Hugs, Catherine
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Catherine, wife of Bruce age 75; diagnosed 6/10/11 with macrocytic anemia, neutropenia and mild thrombocytopenia; BMB suggesting emerging MDS. Copper deficient. Currently receiving procrit and neuopogen injections weekly, B12 dermal cream and injections, Transfusions ~ 5 weeks. |
#22
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Hi Greg-
Ditto on what Al's wife Linda said......I don't think my doctor knows as much about MDS as you do!!!!!! How you are able to interpret all of this stuff is beyond me..... But I know that whatever you do, you have the support of all of us here at MF, and the good wishes and prayers that go with it, whatever you decide! And I do enjoy the "cheese on wry" as well!
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Cheri Age 54; dx Oct 2009 AML, induction chemo only;dx MDS July 2010,- PRBC transfusion dependent; Results BMB 8/4/11--- 6-8% blasts; Danazol 100 mg 3xday; quit Exjade/ GI distress; platelets holding 40's; Fluctuation in blasts in blood--Neupogen 3-4xweek; off Revlimid again! Procrit weekly |
#23
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I can only throw in 1 cent, that would be good luck!
I do agree with your inner cynic though, where drug research is concerned. Deb |
#24
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Revlimid and dexamethasone
Hi Greg,
Yes, of cause Celgene would like all MDS patients to try Revlimid now when they have spent and still are spending so much money on the drug. Here is a study about the effects of Revlimid (lenalidomide) and dexametasone and how they work together to increase red blood cells. I think it is OK to only read the results and discussion. The article is only for personal use but I think members of this forum should know that Revlimid ought to be combined with dexamethasone or a similar drug for best results. http://www.imbhg.tcu.edu.tw/Userdata...in%20CC(1).pdf Kind regards Birgitta-A |
#25
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Hi Birgitta!
Thanks much! I will read this with great interest. I'm getting a pretty big pro-revlimid chorus in my crowd-sourcing, so I need all the info I can obtain about it. I listened to a webinar with Dr. Sekeres from the Cleveland Clinic today and asked a couple of questions about Revlimid, and also about transfusion. One of the tough decisions for me is whether to simply stick with transfusions for a while, since my platelets and WBCs seems to be fairly stable at a reasonable (though not exactly normal) level. If I take Revlimid, I have the chance to decrease my transfusion load, but also the risk of destabilizing my platelets and WBCs, at least temporarily. I know you have said you made the decision to try thalidomide only after your need for transfusion increased to once per week. Did that happen suddenly or gradually? I dropped rapidly from transfusions every four weeks to transfusions every two weeks. Because I am self-employed and have only a short journey to the hospital, every-other-week transfusions are not a terrible burden. I have acquired two blood antibodies, but my local blood bank has found a supplier that can provide appropriately screened RBCs on in 24-48 hours. One concern I have, and that I need to research more, is the impact of acquiring these antibodies on the prospects for transplant in the future. Ihave read credible information that folks who acquire one antibody are more likely than average to acquire additional antibodies, but I am not certain about the impact on transplant. I am not anxious to proceed to transplant, but I would not want to foreclose that option, if antibodies are likely to be a problem. Thanks again for your help! You are a veritable library of great research articles; you must have an amazing filing system. Take care! Greg
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Greg, 59, dx MDS RCMD Int-1 03/10, 8+ & Dup1(q21q31). NIH Campath 11/2010. Non-responder. Tiny telomeres. TERT mutation. Danazol at NIH 12/11. TX independent 7/12. Pancreatitis 4/15. 15% blasts 4/16. DX RAEB-2. Beginning Vidaza to prep for MUD STC. Check out my blog at www.greghankins.com |
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