When it is time to treat, what is your best option for frontline therapy?
FCR (fludarabine + cyclophosphamide + Rituxan) has become the “gold standard” for treating chemo-naïve CLL patients. This powerful chemoimmunotherapy regimen pioneered at M. D. Anderson gives very high percentage of responses – and even more important to us chickens, it gives high percentage of remissions with no trace of minimum residual disease. Which in turn means patients often stay disease free for long period of time without relapsing. We will be discussing all the pros and cons of FCR protocol at our upcoming Workshop on August 14th, 2010.
But is there a way of improving on FCR? For example, can we drop the ‘mouse juice’ of Rituxan and use instead the fully humanized monoclonal ofatumumab (“Arzerra”, Humax-CD20)? Lord knows we went to enough trouble to get FDA approval for this new monoclonal antibody. It seems to cause fewer problems of hypersensitivity in patients (it does not have any snippets of mouse protein in it, being a fully humanized monoclonal antibody) and it seems to work better than Rituxan, on account of hanging on more tightly to the CD20 marker.
And I think some of our guys can benefit from getting into a maintenance regimen of ofatumumab after they are done with the usual 6 monthly cycles of “F+O” or “FC+O”. This approach of a maintenance regimen was used effectively in the recent FCR-Lite protocol. Can we combine the normal six cycles of F+O or FC+O with continued maintenance of ofatumumab – a way of getting more patients into deep and long lasting remissions? Is this going to remain nothing more than my “Dream Protocol” since insurance companies are likely to balk at paying for all those expensive ofatumumab infusions?
Standard of Care at the NIH
Many of you have volunteered for the NIH “Natural history of CLL” study. We reviewed that study earlier and I strongly urge you to read our review as well as the extensive comment section that follows. The natural history trial monitors patients from the time of enrollment to the point where their disease has progressed and requires treatment.
The feedback I got from all our members who were accepted into the trial has been rave reviews. What is not to like? World class experts, detailed monitoring, patient friendly staff, all of it paid for by your tax dollars – no money out of your pocket and no hassles with your insurance company. I admit, it is a bit of a drag if you are not in the Bethesda, MD area and have to schlep your way here for periodic appointments. On the bright side, they do try to help with even that, put you in touch with generous volunteers who will put you up for free if you need to stay overnight. And if you happen to come to MD, you can come and visit me, buy me lunch. I swear I am a cheap date, given I am a vegetarian and don’t do three martini lunches.
When it is time to treat
So, the million dollar question we discussed back and forth in the comments section of our earlier review was this: what happens when the patient has progressed and needs therapy? What are the therapy options available at the NIH? I am not surprised that most of our members who are in the natural history trial would like to continue being monitored and treated by the same team.
I am delighted to report that it is now possible that many of our guys to have their cake and eat it too – continue being looked after by the NIH team, and at the same time have access to the “Dream Protocol” we discussed above. From my admittedly biased perspective as a CLL patient advocate, I cannot think of a better way to spend our tax dollars – especially in these tough times when many of our members are financially challenged and insurance companies have not quite become patient-friendly.
More therapy if you need it, less if you don’t
How smart is that? Simple concept when you think about it, risk adjusted therapy. I am glad to see it put into practice in this important clinical trial.
In a nutshell, patients enrolled in this clinical trial will be treated with 6 monthly cycles in the “induction” phase of the protocol. Those with good prognostics (as in good FISH results) and low risk disease will get just F + O. No cyclophosphamide for these guys. Patients with high risk disease (11q and 17p deletions by FISH test) will get six cycles of F+C+O.
I wish I had a dollar for each time our members raised the question of F+C+R versus just F+R. Which is better? Do we really need to add cyclophosphamide? Well, that depends on whether the patient asking the question is a high risk case or a low risk case. Addition of cyclophosphamide makes sense if the patient needs it to tame a high risk version of CLL. Many experts feel that addition of cyclophosphamide to FR is helpful in treating high risk patients with 11q or 17p deletion. But why take on the extra toxicity of cyclophosphamide if you don’t need it? I am glad to see this clinical trial takes that particular issue into consideration, tailoring the drug combo to suit the needs of the individual patient. Patients will get six cycles of F+O if they have good FISH prognostics; they will get F+C+O if they have either of the two bad chromosomal abnormalities, 11q or 17p deletions, as detected by FISH test
Consolidation after induction
At the end of the 6 cycles, patients who still have minimum residual disease (“MRD” positive, tell-tale signs of remaining CLL in their blood or bone marrow), will be given maintenance therapy with ofatumumab infusions in a “consolidation phase”. There will be four extra infusions of ofatumumab, given every alternate month. Once again, the emphasis is on giving more therapy for those who need it, not to those who do not need it. Makes sense, does it not?
I like ofatumumab consolidation a whole lot better than the previous attempts by other researchers using Campath (alemtuzumab) consolidation to mop up remaining CLL in patients who fail to achieve MRD negative status after FCR or R+HDMP (high dose methylprednisolone) etc. Campath is a hugely immune suppressive drug that causes long term depletion of T-cells, with high risk of opportunistic infections – especially viral infections. And yet, not everyone gets squeaky clean MRD negative remission after FCR, and chances are good that the same will be true of FC+O as well. Getting more of these not-quite-done patients into deeper remissions is very tempting, if it can be done without paying too much of a price by way of toxicity. Ofatumumab maintenance may be that perfect Goldilocks scenario – not as immune suppressive as Campath, but hopefully more effective than the Rituxan maintenance attempted in earlier FCR-Lite protocol.
NIH clinical trial protocol
You can read all the official details of the trial at the link below.
The inclusion criteria are pretty straightforward. The trial is open to patients whose CLL has come to the point where it needs therapy, for the first time. Patients with hepatitis or HIV infections or where the CLL has transformed to other forms of lymphoma etc are not eligible. Active autoimmune disease (AIHA and/or ITP) are also grounds for exclusion, as is any serious chronic medical condition such as COPD, cardiac issues etc. You do not have to be in the prior natural history of CLL trial in order to be eligible to volunteer for this one. Please read the clinical trial protocol details carefully to get all the details.
Let me point out the bad news right up front. The trial is open to only 46 patients. Bummer. I would like to see several hundred patients inducted into this trial. First come, first served. Contact information etc is given in the clinical trial citation. Please don’t make pests of yourselves by swamping their phone lines, but if this trial is of interest to you I think you should not dither too long before sending them a detailed, thoughtful, to the point and clear email expressing your interest. You need to be patient since they can screen patients only so fast. If your situation is such that you need to be in therapy right away, I think it will be a good idea to let them know that in your introductory email – perhaps they will get you to the front of the line and schedule you early.
I like the careful prophylactic protection offered patients in this trial. Bactrim to protect against bacterial infections, acyclovir to prevent herpes zoster (shingles, in layperson terms). If patients become neutropenic (it is almost guaranteed a certain percentage of patients will become neutropenic), growth factors such as Neupogen and / or Neulasta will be used at the discretion of the medical team and as needed.
The trial calls for three bone marrow biopsies. The first one is before starting therapy. If you are already enrolled in the earlier NIH trial on the natural history of CLL and had a bone marrow biopsy done as part of that trial, you may be able to skip the first BMB of this new trial. The second BMB is in the middle of the 6 monthly induction period, to see how you are responding to the therapy. The last one is at the end of the six month induction phase, to see how well things worked out, whether there is still minimum residual disease lurking around in the bone marrow and therefore whether you need to be in the maintenance (“consolidation”) phase.I am not a big fan of BMBs, not unless they are done for good and solid reasons.
I have to admit I cannot argue with the logic of the need for these three BMBs in the protocol.
Folks, this is a research clinical trial. The results from this trial will influence what becomes the next and improved definition of a “gold standard” for CLL. You will be doing a huge service to future generations of CLL patients by participating in this trial. The results will be that much more valuable if they are detailed and credible. So, please consider putting up with the very real pain-in-the-butt involved in getting a BMB. I promise you it is not as bad as you think it will be, but it is no simple blood-draw pin prick either. Think of all the good you are doing as you present your backside to the sharp needle. Scratch that altruistic and idealistic itch you have had all your life. Do it for the fat lady.
Along the same lines, I am very pleased that Dr. Ron Taylor of the “Shaving Reaction” fame will be joining Dr. Adrian Wiestner in doing detailed research analysis of the samples collected. (Dr. Clifton Mo of the NHLBI is the principal investigator, working under the supervision of Dr. Adrian Wiestner). I think very highly of both of both Dr. Taylor and Dr. Wiestner, and however it turns out, we will be able to trust the results coming out of this clinical trial. By the way, Glaxo Smith Kline will be providing all the boat loads of ofatumumab free of charge for this trial, and they will also be picking up the tab for Dr. Taylor’s research. Hey, every little bit helps.
Last but not least, if you are lucky enough to be inducted into this trial do be sure and let us know how it works out for you. I am counting on you guys to keep the rest of us informed, OK?
50 comments on "Better than the “Gold Standard”?"
ANNETTE
Chaya,
Are “Normal” FISH results ( all 4 deletions – are within the (…*…) ) considered “good” or “bad” prognosis ? In aadition to very high CD38 and ZAP-70 ?
Will Guido need the C in FCO ? 1st time treatment.
Thanks
Annette
Too bad, use of monoclonals does exclude you in this trial. We were ready to sign up! Beth
The discomfort from a BMB is way overblown. I had one with only a local, and it was no big deal. You feel pressure and just a minor jab that lasts only a few seconds. (This assumes the technician knows what he/she is doing–mine was at Mayo Clinic and they are real pro’s.) This part of the protocol should not be a deterrent to the trial if you are otherwise interested and eligible.
Annette:
After talking with Dr. Wiestner it is my understanding that the addition of cyclophosphamide depends only on 11q and 17p deletions. But you had better check with the researchers themselves if this is an important issue for Guido.
Jim:
I agree with you about BMB pain being overblown. My husband had 3 bone marrow biosies at M. D. Anderson, no big deal at all. I am told it is a good idea to walk around a bit right after the BMB so that one does not “freeze up”.
I started the FO series at NIH yesteray since I do not have 11 or 17q deletions. I am the second person in the trial (the first woman -hear me roar!).
The first day is the Ofatumumab infustion. I was at the hospital for about 10 hours. The infustion itself took about 6 hours. They infuse it very slowly to advert or avoid drug reactions. While I dreaded getting treatment and avoided it as long as I could, I am happy to say that I did not have any negative reactions from the drug. Once they put me in a bed, the bendryl kicked in and I actually slept most of the day. They did draw about 25 tubes of blood throughout the day. We are stayng in Georgetown and I was asleep again in an hour after I got home. I am pretty sensative to benydryl.
The team of doctors checked on me several times throughout the day.
They too seem to be very excited about this study.
Today I started Fludarabine and again can report no negative reactions. This infustion only took about 30 minutes but we were at the hospital about 3 1/2 hours. Most of that time was waiting on the pharmacy to get the drug upstairs.
The nurses in the day hospital, like everyone else I have dealt with at NIH are extremely capable and precise in everything they do. It is apparent that NIH is a good place to work because you can see it in their employees.
I am happy to say that my WBC started at 315K yesterday morning and dropped to 230K by the end of the day.
I live in Tulsa, OK and it is a hassle to travel to Bethesda. I work more than a full time job. But, I feel like this commitment is well worth it to be in some of the most brilliant minds in the world for CLL. I am very fortunate that Chaya posted the Natural History study otherwise I would not be here today.
I will keep you posted on my progress
I started at NIH through the Natural History study and have particiated in a couple of other research trials during the last year.
Beth:
Yeah, many of us (including me) considered single agent Rituxan maintenance as pretty much a free lunch. Definitely not the case. It rules out some good clinical trials (such as this one), and people with prior exposure to lots of Rituxan do not do as well after more powerful combos such as FCR or FR. I am still looking for that “no cost” therapy option.
Karen:
Way to go!! You are my kind of a woman. I am glad you have good things to say about the NIH and the folks who work there. I have visited several times and been very impressed – but then, I was not facing the pointy end of an infusion needle. Keep in touch and let us know how you are doing.
Thanks as always, Chaya, for being such a strong advocate for us in the CLL community.
I find myself in a quandary…I was diagnosed in 2005; Zap 70+, unmutated, normal FISH. When I saw Dr. Kipps in March, my WBC was 97,000, Hg 12.8, all other counts well within normal; B2m 2.8; very little node involvement. Dr. Kipps assessed me as Stage I, bordering on Stage II with just a spleen tip palpable. At the end of June, my WBC was 127,000; Hg was 12.9….all other counts normal; slight fatigue. When I asked what he would do in my situation as far as treatment, he advocated for monolonal antibodies……not FCR. His reason was the damage to the immune system.
I find myself with a very real resistance to FCR……so I look forward to hearing what comes of your workshop. Wish I could attend as I’m sure it will be very productive!
Please excuse me, but I am a bit confused. Is this a trial to see if FO and FCO are comparable to FR and FCR? I don’t remember there being any studies of FCO that showed equal results let alone “dream” results.
I know there is still doubt on whether maintenance R after FCR (regular or lite) actually has any long term benefit. If this is true, then what will this study compare itself to, regular FR and FCR?
I know logic dictates that since O binds more tightly to the dim CD20 it must be better than R, but logic is seldom right especially in combos.
So again, it may just be my ignorance but has there been any FCO or FO studies that I have missed? If anyone has any info, please let me know!
Best Regards,
Tom
Tom:
Earlier clinical trials have shown that single agent ofatumumab is effective even in patients who had relapsed after fludrabine, and had prior exposure / resistance to Campath (or Campath ineligible because of bulky disease), compared to historical data on single agent Rituxan. This is a tough group of patients and the results of this trial were the basis of ofatumumab approval by the FDA. By comparison, Rituxan does not give the same level of response even in chemo naive patients and is next to useless as single agent in refractory patients.
Rituxan maintenance may have been effective in the latest clinical trial results reported for FCR-Lite. It is also now generally accepted that getting patients into MRD negative status is a good thing, that such remissions are likely to last longer and put off the need for additional therapy.
So, the logic goes, if O is more potent than R, then FCO may be better than FCR. If R helps maintenance, O may do it better, get more patients into MRD negative status. All this with lower risk of hypersensitivity to murine (mouse protein) since ofatumumab is fully humanized.
Is this trial as credible as two arm trials comparing strictly head-to-head (1)FCR versus FCO (2) FR versus FO (3) FCR + R maintenance versus FCO + O maintenance? Obviously NOT!! Is anyone getting ready to do any of these large scale double arm trials at this point in time? The answer is NO. Even the M. D. Anderson study with large number of patients, the one that anointed FCR as the modern day “gold standard”, was a single arm trial and the results of that single arm trial were compared to historical remission statistics of earlier trials using just FC. Fortunately for us, the encouraging leads provided by the MDA single arm study lead the German CLL study group to do the pivotal FC versus FCR comparison in a large scale and well designed double arm trial. And that settled the question once and for all: FCR beats FC hands down.
It is to be hoped that if indeed this FCO + O remission yields longer remissions and longer survival statistics than we see presently even with FCR, then some research group with deep pockets and large grants may be tempted to do the definitive double arm trial.
Clinical trial information is hard to come by, double arm trials are almost prohibitively expensive. No one is going to do them without prior information pointing to a possible success. I think there is enough evidence pointing to the possible improvement of using O versus R, and enough evidence pointing to the value of getting more patients into MRD negative status (without a huge increase in immune suppression on the cost side of the equation, of course, as is the case with Campath consolidation) to justify my excitement about this trial. Whether your comment was based on good faith desire for information or just a teeny bit on the snarky side, I too wish there were more large scale and randomized double arm trials being done today. Only time will tell how this combination will play out. On my part, I could be wrong but I am willing to bet FCO + O maintenance will be an improvement on FCR. Incremental improvement, but improvement nevertheless. I am also willing to bet fewer patients will develop hypersensitivity reactions ofatumamab – as my husband did to Rituxan.
And did I mention that since this trial is being done at the NIH, patients who have insufficient medical insurance and yet need frontline therapy for progressing CLL finally have a good therapy choice they can afford? No pesky co-pays, no insurance company hurdles, less risk of incompetance from local oncologists that may not have kept up with all the new fangled stuff coming down the turnpike. All of these reasons makes it a dream protocol in my book.
Chaya
Thank you for the very informative article. This sounds like a great trial and to have it at NIH is really perfect. I wish that they would do one for relapsed patients as well.
Sorry I cannot make it for the conference. Would love to be there.
AA
Hi Chaya,
Thank you for the great response. I was not looking for a double arm study. I was honestly hoping there was a single arm study that I missed.
I am with you 100% on these topics:
Single agent O is better than single agent R.
Ofatumamab should have drastically less hypersensitivity and that could even mean more shots at using for a longer period.
This trial is great in general. It should be able to give some insight into initial response rates within the next few years AND makes the therapy available AND makes it affordable for those that need it.
Am I sold that FCO + O is a dream? No, but I hope it is for those who are chemo naive or even refractory!
As to why I might have come across badly? I just started FCR therapy 3 weeks ago and REALLY struggled with the decision. I was looking for any research that showed equal or better responses with less toxicity but couldn’t find it. I pushed off therapy an extra 4 months while researching. I was afraid I missed something obvious.
I’m 42 and feel my first remission (knock on wood) will be my best so I’m trying for my best shot at mrd-. I’m in the process of signing up for the Bexxar consolidation trial that you had mentioned a few years ago (changed to just consolidation from full FR+B).
At this point my strategy is FCR then Bexxar consolidation. If there isn’t a cure or something that doesn’t use up bullets by the time I fall out of remission (knock on wood), I will be looking at a voluntary mini-allo. Yes, it may be silly to plan what is hopefully very far in the future, but that’s just the way I am.
Wow, am I grateful I went with my gut feeling when the first local oncologist told my husband and I that the “C” in FCR is only given at major teaching medical centers and 11q del patients do just as well with FR. He received only 4 FCR cycles (due to severe thrombocytopenia)starting in June ’09. Although the BMB is free of 11q cells, they did find 20q del first 6, then 8, now 12 on samples. The pathologist warned his oncologist that this is suspicious for MDS. Is there a chemo treatment for 20q del since it was caused by chemo? How common is a 11q treated patient that develops MDS?
Tom:
I hope the FCR + bexxar chaser for consolidation works well for you. It is clearly a logical choice. But the concern with radioimmunotherapy drugs such as Bexxar and Zevalin have always been the same thing: bone marrow toxicity as collateral damage if the patient still has significant CLL cells in the bone marrow. Unless the patient is using Bexxar to tee up for a mini-allo transplant (where the host immune system is discarded anyway), collateral radiation damage to presious stem cells can be a huge issue – unless the FCR / FR induction therapy yields a clean bone marrow remission.
Do keep in touch and let us know how it plays out for you. At 42 you are a very young patient and you are entirely right to be doing what you are doing, thinking outside the box. Incremental control of the CLL wil only help deplete your therapy choices and leave you with no bullets left to fire. FCR + Bexxar consolidtion (if the remission after FCR is clean) is an excellent choice. Don’t second guess yourself now.
Good Luck to everyone who gets into this trial! My husband, Tom, was in the MDAnderson FCR trial that made it the gold standard. Tom really falls outside the norm so I feel that I should mention a few things about R vs O.
Tom had MRD after 6 treatments with FCR and relapsed at 2 years from the last treatment. With many treatments since, he has shown allergies to Rituximab, Lenalidimide and Ofatumamab. In fact, Ofatumamab gives him the exact reaction that Rituximab did which is a barky cough for 2 days following and chest tightness. The one difference is that the Ofatumamab’s reaction is delayed by one day or so. Tom is asthmatic and highly allergic and CLL is causing all kinds of problems in this area.
Dr. Michael Keating made some positive statements about FCO during one of our past visits. It makes great sense to me because we are now rid of the mouse problems.
Thanks to Chaya for posting this and to the brave warriors entering this trial. Trials are the only chance of finding the REAL CURE! And trust me, you won’t get better care! I feel that trials are the only way to go…..
Jenny Lou
Chaya,
Thank you for letting us know about this very hopeful trial. I have read through the trial via the official link, but cannot find any discussion of mutation status. Will mutated vs. unmutated be considered in eligibilty for this trial?
My husband is also enrolled in the NIH Natural History Study and so very pleased with the doctors and staff at NIH. I can’t thank you enough for sharing that opportunity at such a critical time in our lives and during such a gut-wrenching time in your life. Participating in that trial seems to have saved us from the agony that we read from others in this group who have had less than productive experiences with their treatment providers.
See you at the workshop.
Kathy
kafreela:
I do not believe IgVH gene mutation status influences eligibility to enrol in the trial. It may not even influence whether the patient gets F+O or FC+O – but you had better check on that with the researchers.
Its great your husband is happy with how the Natural History of CLL study is working out for him. Now with the start of this new therapy tral at NIH, when and if he needs therapy he will have another good option to consider.
Thank you Chaya. We’ll check with Susan Soto regarding the mutation status criteria and Halleluiah for Options!
The BMB I went through at MDA was worse than giving birth. I nearly climbed through the roof because I was crawling off the top end of the bed. The nurse kept on apologizing, and it was not the first time she had done it.
It depends on your lymphocyte count I think. They had more than the usual number of tubes to fill. The bone biopsy was nothing. Next time I will ask for an anaesthetic. Just reading the word BMB sends shivers down my spine.
Just for balance, I’d like to offer my experience with BMB. Although done at a Cancer center, it was done by a medical student as a first time experience under step by step supervision of the Resident. It was nearly pain free and I felt impelled to compliment her performance to my oncologist. At my center you are offered the option of a mild sedative prior to the procedure which may have ameliorated the situation described by Musikrite. Anyone needing this procedure should not assume the worst.
Hi Chaya,
I have now had 6 BMB and after the 4th one done under local and finally could not take it any more and went full anesthesia. All of mine were done by very experienced doctors. I had never experienced pain like that. I note the varied experiences discussed above and would suggest that each person has a different tolerance for that kind of pain. I have a really good pain threshold but when it comes to digging into bones or breaking bones I don’t do to well.
Hi, I absolutely agree with the last comment about each person having a different tolerance for the pain during a BMB. I have had many BMBs and they were initially so painful I too compared it to childbirth pain (and we are talking 19 hours of childbirth here!). I have been told I have ‘bone like concrete’, with a doctor wrenching a wrist, another saying they have done ‘hundreds’ and never found anyone so problematic.
We are all different (as is evidenced by the way CLL affects us all differently) – for those of you who find a BMB a walk in the park, consider yourselves very lucky.
Thanks, Jaqui for better expressing the point I attempted to make about the diverse reactions we experience.
Seems to me everyone’s experience with BMB is different and has more to do with you, your physiology, and your level of pain tolerance. All of my BMBs have been done by my hem/onc. My first 2 were done under full anesthesia and I slept the day away. For #3 I asked for a local only. I felt no pain from the needle going into skin and bone; only brief discomfort from the extraction, but my assisting nurse massaged my feet and ankles and that helped to calm me down. For #4 that nurse was no longer at the cancer center so I brought a friend to do the massage. For any future BMBs I know I can handle it on my own just with deep/relaxing breathing. I’ve never borne any children so maybe my hip bones are thinner than that of a woman who’s had to support the weight of a growing fetus. I know my tolerance for pain is pretty strong so that’s another plus. I do know that I’ll never have another BMB with a full knockout again.
Betty
Ofatumumab – who makes up these names?! That one’s the worst yet.
PhilB:
Believe it or not, there is a naming system for these drugs that the manufacturers must follow. Just as there is a naming system for chemical molecutes, modern drugs must also follow a naming system.
http://en.wikipedia.org/wiki/Nomenclature_of_monoclonal_antibodies
The “mab” ending refers to the fact that this is a Monoclonal AntiBody. In the case of “ofatumUmab” the “U” in front of the “mab” points to the fact that ofatumumab is a human anitbody – unlike Campath (“alemtuZUmab”) where the “ZU” stands for a humanized antibody that started life as other than fully human. Rituxan (“rituXImab”) has the “XI” in the middle, pointing to the fact that it is a chimeric anitbody – which means it is part human and part mouse in this case. All three, ofatumumab, alemtuzumab and rituximab carry the “mab” ending, as one would expect.
For the layperson this is a lot of jargon. But for professionals this naming system is very important. I taught freshman chemisty for several years – my students complained about the IUPAC international naming system for organic molecules – and yet it is absolutely essential if scientists are to keep things in order, given the explosion of new molecules invented each year. For some large molecules the official name may run into several lines and look truly bizarre. But trained organic chemists can draw out the complicated structure of the molecule just by looking at the name.
I refused to have the last BMB because the first time the pain was so intense. My friend who was with me said the nurse looked as if she was drilling into my back. I have had four children,(at home, with no pain relief needed) so maybe I too have ‘concrete bones’.
I have had one BMB performed by my local hematolgist/oncologist. I had a very brief moment of pressure-like pain that was not intolerable. The key is having an experinced clinician perform the procedure. Getting control of anxiety is also helpful. I do not have a high pain tolerance, I have fainted after hitting my “crazy bone.”
You can tell a good bone marrow biopsy by the color. A good one will be almost clear, like serum from blood. Cerebral spinal fluid is not part of the blood system. Unfortunately most of the CLL biopsy samples I have seen were part red or all red, meaning they missed a bit. I would be interested if this is a difference in the people who experienced tolerable pain with those describing extreme pain. Since the donor is in no position to see the sample as it is being drawn, maybe this is not feasible. No doctor wants to admit they don’t have great hands but maybe more people would agree to them if they were done by specialists used to doing marrow transplants than CLL hematologists.
In trying to make excuses for these bloody bmb samples, I mixed the two types of marrow. Bones other than the spine are largely responsible for the production of blood and stem cells. Maybe I was asleep in class, but I was not aware than we make 500 ml of cerebrospinal fluid (CSF) and it turns over 3.7 times per day. The reference range for RBCs in CSF at the wiki page goes from n/a to zero. Maybe someone else has a better explanation, but if they are drawing a red sample, that huge needle may have gone through the spinal cavity.
For those who dont’ like to click links:
n. (Abbr. CSF)
The serumlike fluid that circulates through the ventricles of the brain, the cavity of the spinal cord, and the subarachnoid space, functioning in shock absorption.
Britannica Concise Encyclopedia: cerebrospinal fluid
Top Home > Library > Miscellaneous > Britannica Concise Encyclopedia
Clear, colourless liquid that surrounds the brain and spinal cord and fills the spaces in them. It helps support the brain, acts as a lubricant, maintains pressure in the skull, and cushions shocks. Analysis of CSF obtained by a spinal tap (lumbar puncture) helps diagnose a number of disorders, including meningitis and hemorrhage in the central nervous system.
Sorry to spam, the reference ranges for CSF was on the answers.com page:
Reference ranges in CSF
Substance Lower limit Upper limit Unit
Glucose 50 80 ng/dL
Protein 15 40–45 mg/dL
RBCs n/a 0 / negative cells/µL
WBCs 0 3 cells/µL
Less that a month ago I finished a PCO clinical trial at Duke. 6 treatments, one every 3 weeks. The initial results were better, much better than expected. I go back in the middle of September for bone marrow biopsy, CAT scan and final blood work. At that time I will provide a final input on my situation.
I don’t want to see this discussion hijacked by a single topic, namely bone marrow biopsies. I think it is clear that the level of pain experienced by individual patients depends on the experience level of the guy doing the biopsy, the level of anesthesia used, pain tolerance of the patient involved and the ‘hardness’ of his / her bones. In other words, only you can tell how much it is going to hurt. Nuff said.
Do we really need to know the details of CSF fluid composition in order to consider the potential value of this clinical trial? Please stay on topic – we don’t want to overwhelm our readers with tangential information replete with jargon, just to be impressive. Clarity, relevance and thoughtful comments that are on topic – that is what I would like to see in these discussions.
I try hard not to muzzle discussion and rarely block emails – unless they focus on stuff that I consider to be spam or grossly hyped up nonsense. Our software does block comments containing live links and such comments languish in limbo until and unless I or our webmaster takes a look at them. You don’t want to have to deal with a lot of links to porn sites or viagra sales jobs do you? I have a lot on my plate – please refrain from live links if you can; or put up with getting your comment sequestered – sometimes indefinitely.
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Just wanted to give a brief update on the NIH study – FCO/FO. As I mentioned earlier that I am in the FO study because of my good prognostics and am the 2nd person in the study.
I finished up the last infusion of on Monday. The only negative side affects I had was being tired and some loss of appetite, but no nausea, vomitting or fever. The doctors told me that I would start regaining strength within a few days after the final infusion. While I am still tired, today (Thursday) was much better.
There has been one unexpected side affect I didn’t anticipate, it is the emotional side. I am sure that it is the cummulation of the drugs and the physical toll on my body. I have had a hard time staying out of the “dark”. Now that I am actually having to get treatment this disease has become real again. For me, CLL was relatively easy to live with and ignore during W&W.
Fortunately, as I regain my physical strenght, my emotional state also strengthens.
The really good news – my WBC started at 315K on 8/9 and dropped to 47K on 8/16! They told me to expect it to go back up between cycles, but as we know, by the end of the 6-cylces we want completed response with no minimal residual disease.
NIH – FO study
One week after the first treatment and good news on the CBC – wbc has dropped further to 31K. Just as exciting is platelets, hemoglobin, neutrofils, rcb have all increased!
I am working all day but I still don’t have the energy level I had before treament.
Just hoping progess continues.
I live in Minnesota and tomorrow have visit an Oncologist at Mayo Clinic to discuss treatment options for my CLL. I believe Mayo has a similar trial as NIH but using Pentostatin vs. Fludarabine.
While I would love to participate in the trial you mention above, distance, time away from work, and travel cost, makes that an unlikely scenario.
Wondering if you have any additional thoughts or information regarding Pentostatin vs. Fludarabine. I believe I would fit the FO program at NIH given my type of CLL.
I know you’ve written about P vs. F and indicated the F is preferred as it has been shown to be less toxic.
Also wondering if you have an opinion regarding a choice of FCR (if I have that option) at Mayo, or PCO (Mayo’s clinical trial). Personally, I prefer ofatumumab over rituxan, but also prefer Fludarabine over Pentostatin. So, (hopefully) I have a choice to make.
Thanks for all your work. You help us lay people more than you realize.
pllouwagie:
I have nothing further to add on the subject of fludarabine versus pentostatin. There is no additional data to report, as far as I know.
But I would like to clarify something you wrote – “F is preferred as it has been shown to be less toxic”. That is NOT the case. In fact, some researchers believe pentostatin is easier to tolerate and less toxic than fludarabine. However, this has not been proven conclusively.
In the absence of clear cut proof that either of these two drugs is less toxic than the other, I tend to lean toward fludarabine since it hsa been more thouroughly explored in combinations such as FR and FCR. The better known devil etc.
An update on my FO treatment at NIH’s study. I finished round 2, two weeks ago. My WBC is 3.7 and all other counts are in the safe range. Keep in mind that I started at 315K! Lymph nodes have shrunk with only a few still noticable.
I seem to have gained some weight back that I lost during the first round. I still struggle with constipation but drugs help that too.
I felt almost normal just before the 2nd treatment and through the first two days, however, after the third treament I started feeling more tired and felt that way until the forth day after treatment when I saw significant improvement. I would say I was at 50-60% for three days after treatment and by the forth day back to 80%.
Today (13 days after the last infusion)I felt well enough to run the Susan G Komen Race for the Cure with my cousin who is a two time breast cancer survivor. I haven’t run in a year and a half and I had expected to just walk it today, but I didn’t.
Only four more rounds to go! More to come
Round three is a week behind me now and I am feeling much better. There seems to be a pattern established with starting to feel more tired after the third infusion and a little nausea after the 5th infusion. It takes about three days for me to see an improvement of my energy level.
I was midly neutropenic three weeks after round two – it will be interesting to see how that plays out this month.
Lymphocytes are in the normal range for the first time since diagnoses in 2006.
There are now four people in the study and I was able to meet another one of the lab rats. I hope the others don’t mind that description.
The Docs asked me if I could see an improvement in my engery level now in comparison to before I started treatment. I can now say that may be true. I do believe my energy level has improved to pre chemo level.
Round four – done. At this point I am hoping to avoid neutropenia. So, far I have not had to take any neupogen. This week, my wbc was 1.1, neuts .8 *(which is the lowest it has been throughout treatment). However, the percentage of neuts are now within normal range. This decline appears to be expected and then builds back up. RBC is still below normal but hemoglobin is finally in normal range. My lymph nodes are almost completely gone. I am a thin person so they are very easy to detect.
This last trip was another bone marrow biopsy. This was my third. The first one at diagnoses here in Tulsa and it was grueling. The second at NIH when they also removed my lymph node so I was asleep. This last one was part of the study and for research purposes. Janet Valdez did it and it was not nearly as bad as I had expected.
As of this last trip, there are still only three people in the study. There was a forth but that person dropped out. To anyone considering this treatment option, the time away from home is a big commitment and it is good to have a support system. But, I truly feel that the opportunity and experience is well worth the sacrifice. I personally have been very fortunate to have build a personal support network in the area.
Everyone at the NIH clinic continues to be incredible. I am getting the very best of care from the docs, nurses, administration, even the folks who deliver your food and take out the trash are friendly and considerate.
Once I finish the protocol they will do flow cytometry to determine if there is any minimal residual disease (mrd). If there is none detected I will go on a follow up program. If there IS mrd – I will get follow up treatments of ofatumumab.
The fact that there is no mrd, does not mean that the cll is all gone (unfortunately)it just means that they can not detect any cells. The goal is to get a LONG remission.
HURRY UP AND FIND A CURE FOR CLL!!!!! This whole cancer thing is really getting in the way of me living my life! Bless you all!
So grateful to Karen for her posts on her NIH treatment. I’m part of the NIH Natural History Study and a candidate for the treatment when my time comes, so this reporting is extremely valuable. I second her emotion re the NIH staff. They are incredible and one of the main reasons that I will probably choose the NIH treatment protocol when my time comes. Also want to give kudos to Dr. Farooqui, the current Fellow doing a lot of the front line patient exams for the Natural History Study. He did my BMB and it was a non-event. I would prefer it to most any dental work, any day. I had heard from Susan Soto that he was good, but I told him afterward that I’d stand up and give him a testimonial any time he needed it. Guess this is that time. Unfortunately, my BMB showed by CLL infiltration at 80-90%, so I can see I may be spending more time at NIH in the near future; but one thing we know about CLL .. there’s really no way of predicting exactly when that will be.
I have some questions for Karen61, as I may become a participant in the FO trial at NIH in 2011. I also have to make a medicare RX plan choice this month and the plans are all different, with different drug coverage and discounts.
So Karen .. here they are:
1) Does NIH provide most / all of your oral meds?
2) If not all, which ones did you and your insurance have to buy?
3) Did you have to do a pre-treatment conditioning? And if so, what drugs and were they provided by NIH? In particular, with your high WBC, did they put you on allopurinol or something like it? (I am blessed with a very high WBC as well).
I’m sure I’ll have other questions if and when I become part of the trial. Your posts are great and you clearly have a wonderful spirit. Hoping for all the best for you.
Karen .. Chaya has my email address if there is anything you would like to pass on in addition.
Karen61 and LynnS:
This is the kind of back-and-forth exchange I like to see between patients undergoing therapy right now and those who are contemplating it and would like to learn from others’ experiences. Sharing our experiences in an adult fashion helps everyone in our patient community. Thanks!
While my articles are open to the general public, only registered members who login can read the comments that follow. We chose that policy to give you guys some level of privacy. My own privacy has been shot to hell a long time ago – part of the cost of running this and the http://www.clltopics.org websites.
But I still want to caution you against putting your email addresses, phone numbers etc in your comments. Updates has become an important site and I am pretty sure there are many robots crawling over the site for data mining on any given day. If you put your contact information out there, be prepared to get a lot of spam and drug company marketing emails.
This much I can guarantee: we will never, ever, share our member registration database with anyone. You will not get spam from us. We will not try to “sell” you anything (other than using every trick in the trade and nagging you to take better care of yourself).
If you wish to establish direct email contact with any member, just write me and I am happy to make the introductions – without publishing your contact information to the world at large.
Chaya, I appreciate you sharing the above as a reminder on both aspects of sharing information but not the personal contact information. Additionally, thank you for making contacts with each of us individually.
LynnS,
NIH provides all medication during the treatment. Yes, they put me on Allopurinol during my first treatment since my wbc was so high. It was interesting, because my oncologist at home (Tulsa) was going to reduce the wbc before starting FCR (just to clarify, I did not choose treatment at home). She was certain I would get tumor lysis, which I did not.
Feel free to contact me if you want and Chaya so graciously agreed to put us together. You might give me a few days though to recover from the trip and treatment.
thanks
I am now in round 5 of the FO treatment at NIH. I had a delay in treamtent this time due to ANC being too low. THe normal schedule is I fly her on Wednesday morning and go to clinic that afternoon. The doctors decided to give me a Neupogen shot and the ANC count went from .7 to over 8K after only one shot. Fortunately, I was able to start treatment with only one day delay. My CBC is all over the place right now; I am sure it is caused by the Neupogen.
I did wake up this morning with a sinus infection, which is a slight concern. They gave me medicine to help with that. While, I don’t feel horrible during treatment, I am more tired, and having this sinus infection is an added pain. I will most likely be on the sofa today just resting.
Update after round 5- the sinus infection progressed into a fever, but it seems that having had already started taking antibiotics, we were ahead of the game. I seem to be taking a little longer to feel better after this treatment. I am sure the infection hasn’t helped. My energy level has decreased also although it improves daily.
I noticed just before heading back to Bethesda for this trip that I was feeling very well. I decided I would take the stairs at work from the first floor to the forth floor, which is something I have done the 6 years I have worked there. I could only make it to the third floor. It will get better soon.
All the Docs were are the ASH conference for most of my treatment. I look forward to hearing their perspective on the trip.
I was supposed to start my sixth treatment on Thursday but we delayed treatment due to neutropenia. They want my body to recover before hitting me another dose of chemo. The low ANC was .41 and was .51 last Wednesday which was four weeks after the previous treatment. Platelets were at a new low this past week too.
I continue to work every day with some days being 10 hour days, but I have nothing left when I get home. I am completely wiped out.
What I find interesting and I have not had a chance to ask the question, is that they apparently prefer NOT to use the Neulasta to boost the neutrofil count. So, due to this occurence, we are on watch and wait again until counts go back up to a safe level. Go figure; ironically, I am not a very patient person, but we all have lessons to learn I suppose.
I did get to briefly ask Dr. Farooqui about the ASH conference and they are now working on a couple of exciting new studies as a result.
The new year brings to us a time of hope and anticipation. I feel like CLL patients have a reason to hope and can look forward to many new exciting treatments that will lead to very long productive lives. I am actually expecting a cure before I need treatment again. Remember- I am the optimist!
More updates to come.
Happy New Years to you all!
Karen,
Wishing you all the best in 2011 with your treatment and beyond. Thank you so much for the posting you have been doing as some of us may be following you down this path at NIH. Please take good care of yourself while the neuts are lower than you’d like.
Lynn
Neuts back to 1.1 – back to Bethesda to finish up the treatment!
I am remiss in the update of my final treatment. I did get the round 6 on Jan 12th. The Dr’s decided my bone marrow was being negatively affected so they reduced the dosage of Fludaribine 25%. What I didn’t realize was that this was the third time it was reduced. Somehow, I didn’t catch that they reduced the dosage the 2nd time and I think it was round three. The previous two times they reduced it were due to kidney function.
I didn’t feel as ill this time after treatment. I don’t know if it was because of the reduced dosage, or the extra two weeks in between treatments or the fact that it was my last treatment. Nonetheless, it was easier. I even went back to work for about 6 hours the day after the last infusion. However, I thought that since I did not feel as badly after this round, I expected to bounce back sooner. Not quite so much… the drugs still had to work their way out of my system and apparently, that is a relatively slow process. Today is six weeks after the last infusion and I would say I am about 90-95% back to normal. I still get tired, but I have much more “get up and go.”
I went back to read my previous posts and thought I would revisit some of my comments.
First and foremost, I am very happy I chose to have treatment at NIH and to be in this study. Yes, I absolutely hope I personally benefit. But, somehow I still feel like I am part of something bigger. I know that my participation helps even if it is a small part to progress and maybe even someday cure CLL.
The time away from home and travel is and was a hassle. I strongly recommend always having a buddy with you when you travel there, whether it be a spouse or a friend. This is cancer treatment folks, you need support not just for the physical reaction but also the emotional part. I have been extremely fortunate to meet many new people in DC that I now call my friends. I have had an army of support there. It was almost as good as being home.
On that note, I would say that I experienced some pretty dark days after treatments. However, as my body regained strength so did my mental/emotional outlook. I had to have quite a few talks with myself to remind myself that these bad days would get better. And they did!
I had the FO protocol since my progostic indicators were favorable. The first round was O on day one, Fludarabine the next five days, one day of rest and O on the final day. The rest of the rounds were O and F on day one, then four more days of fludarabine.
The FCO treatment is only 3 days of infusion. I guess they get an extra kick from the Cytoxen and three is enough.
I went back for a check up four weeks after the final treatment. All is well. Dr Awe, said I have had a “complete response”. I return in May for the re-staging visit. That includes BMB, CT, and flow cytometry to detect minimal residual disease.
I may be forgetting something so feel free to ask me any questions.
Chaya has commented many times throughout her postings about her gratitude to participants in trials and studies. And also her disappointment in those who run the trials and studies for not giving thanks to those patients who participate. So, I am here to say, loud and clear, that the team at NIH has been very greatful and have thanked me for my participation. I have truly felt like this has been a team effort and I have been an active member of that team. So, Dr. Farooqui, Dr. Weistner, Dr. Awe, Dr. Marti, Susan Soto, and Janet Valdez – thanks to each of you.
I will continue to keep all of you informed of my progess and MANY years of remission!
Karen
Karen,
It’s been almost one year. Can you give the world an update?
Thanks
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