Will a “Min-Allo” let you live longer?
Let us agree, right up front, even the “kinder and gentler” mini-allo transplants are not fun, and they are not for the faint of heart. There is significant risk of morbidity (think quality of life) and mortality (as in death). You would not do it if there were better options. So, here is the million dollar question: do mini-allo stem cell transplants save lives?
Two recent excellent articles address this question. The first one from M. D. Anderson gives us a historical perspective. The second one gives the latest survival results and compares them against conventional (non transplant) approaches. I have summarized the salient points from both articles along with my own explanations of the science & jargon where I thought it necessary. Since the review got a bit too long I decided to publish it in two parts. Here is the first installment.
The only CURE
None, I repeat none, of the chemotherapy regimens we have available are capable of producing a CURE for this incurable cancer. No matter how deep the remission, it will end and often it will end sooner than you want. For a lucky percentage of patients it may be possible to run out the clock, string along a series of temporary remissions until your natural life span runs out. If this is possible for you, it is surely the way to go. If you have good prognostics backed up by real life slow progressing or smoldering variety of CLL, if you are already at an age when you did not expect to live several more decades in any case, running out the clock is a terrific strategy. Kick back, enjoy, wish the rest of us chickens good luck.
But for younger patients with families to raise, jobs to go to and mortgages to pay, running out the clock is not an option. If their CLL also happens to be an aggressive variety, serial chemotherapy quickly becomes a losing game with diminishing results. We desperately need better therapy options for this set of our patient population. For now, the only therapy potentially capable of curing CLL is a stem cell transplant (SCT) from a matched donor. So, here are the million dollar questions: is it worth it? Should you consider a stem cell transplant?
M. D. Anderson experience
The article (abstract below) from M. D. Anderson gives a very nice overview of the whole stem cell transplant (SCT) field, by a man who has been in the forefront of it. I strongly urge you to read the whole article, not just the abstract. Write to me (personally) if you need help locating it.
Hematol Oncol. 2009 Jun;27(2):53-60.
The role of stem cell transplantation in the management of chronic lymphocytic leukaemia.
Tam CS, Khouri I.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
The majority of patients diagnosed with chronic lymphocytic leukaemia (CLL) will ultimately die of their disease. Stem cell transplantation (SCT) remains the only treatment modality capable of cure, but has traditionally been associated with very high morbidity and mortality. We review the results of myeloablative autologous and allogeneic SCT in CLL, discuss the evolution of the new non-myeloablative approaches, and make recommendations for when SCT should be considered in patients with CLL.
PMID: 19358149
CLL is the “good” cancer to have, right? So why should we even think about risky stuff like transplants? Experts have been pussyfooting around this question long enough. It is good to have someone of Dr. Khouri’s stature to finally say the emperor is buck naked. For too many patients CLL is an incurable cancer, a killer. Here is a direct quote from the paper, one of many good ones.
“The reality is that a substantial proportion of patients with CLL are diagnosed prior to the age of 60 and 70% of patients diagnosed with CLL will die either directly or indirectly of their disease”.
Wow, how is that for a swift kick in the gut. Sorry, but some of us (and some of our doctors too) need that little wake-up call. A “good” cancer does not need a stem cell transplant. A killer cancer that is incurable by any other means – now that is an entirely different ballgame and we need to think about stem cell transplants.
“Among patients with progressive CLL, those who eventually develop disease resistance to currently available drugs have a dismal survival of less than 12 months. As SCT is the only treatment modality capable of cure in CLL, it is likely that a discussion regarding its use will arise at some point during the disease course in a majority of patients”.
Do autologous SCT work?
Like with all things CLL you have to learn the lingo of transplants. Autologous SCT are when stem cells are harvested from the patient himself and give back at a later time. There is no second party involved, no matched donor giving the gift of his / her healthy stem cells to replace your damaged immune system.
Autologous stem cell transplants have been used in two settings: first as salvage therapy in patients who have relapsed after conventional chemotherapy, and second in an attempt to go for broke and try to eradicate all traces of CLL in younger patients with early stage disease.
Disappointingly, even when auto SCT was attempted early in the ball game, low tumor burden, a chemo-sensitive CLL and all the technology we have to “clean” the patient’s own harvested stem cells (to try and prevent any contaminating CLL cells from sneaking back into the patient’s body) before giving them back to him, there was a continuous pattern of relapse. No one was cured; it was once again a matter of when the remission ended. Khouri et al cite chapter and verse in their seminal paper, vital statistics from many reputable institutions. Same pattern, same disappointing story. No cure.
Think of an auto SCT as very aggressive chemotherapy to treat the CLL and you would not be far off the mark. Yes, the remission may be long (or not), as you would expect with any aggressive combination – say, FCR or CFAR. But like these heavy duty approaches, life after remission ends may become difficult with few good choices.
By now I hope all of our readers are savvy enough to tell the difference between one or two patients who are still in long term remission after an auto SCT and robust, statistically valid data such as presented in the Khouri article. We wish the lucky patients continued good health, but it is foolish to draw comfort from their one-of-a-kind situation. Auto SCT for CLL patients are now discredited and except in rare circumstances they are no longer the recommended for CLL patients in this country or Europe.
Myeloablative allogeneic SCT
I agree, it is mouthful – but not all that hard to understand, if you break it down into little bits. Let me show you how.
“Myeloablative” is full strength conditioning using high does of chemotherapy and full body radiation to rid the patient’s body of as many CLL cells as possible – think of it as the mother of all chemo / radiation combinations to get patient into best possible remission ahead of receiving the precious stem cells gifted by a matched donor. No attempt is made to spare the patient’s own hematopoietic stem cells – they too are killed in hordes. Not to worry, they will soon be replaced by a healthy bunch of donor stem cells.
That is where the “allogeneic” bit comes in. The root words “Auto” means self, and “Allo” means other. By definition, an allogeneic stem cell transplant (sometimes abbreviated to “allo SCT“) involves finding a suitable donor, one who is healthy, willing and able to donate blood stem cells matched to your own cell type.
The first place to look for a matched donor is in your own family, your brothers and sisters (not your parents, not your kids. They would not match). The more sisters and brothers you have, the better the chance that at least one of them is a good match.
Sibling donor matches are the first choice, followed by generous donors who are not related to you but who happen to be a good match. These are called MUD (matched, unrelated donors). Not everyone can find MUD donors as needed, especially if they are from ethnic minorities. Umbilical cord blood is a recent option that became available for such patients. Details of donor selection are described in an earlier article “Matching made simple“.
A small dog-leg in the universal preference of sibling donors is the small risk of getting a second dose of CLL from your donor! How nasty is that?! We know now that CLL is a familial disease, your blood relatives are at significantly higher risk of getting / having CLL themselves compared to the general public. Roughly 13.5% of your first degree blood relatives may have the tell-tale signs of a CLL clone, even if it is so small it has not been clinically diagnosed (and may never grow up and show fangs, may never become clinically relevant). Dana Farber reported in their study 7 sibling donors were excluded because they themselves were at hitherto undiagnosed risk. Going one step further, you will understand it is not a good idea to have your identical twin as a stem cell donor, not without extensive testing to make sure there is no sign of MBL or undiagnosed blood disorder in the donor as well.
The enthusiasm for doing a thorough house-cleaning with full strength myeloablative preconditioning becomes muted when we consider very high treatment related mortality (TRM) statistics. It is a case of the cure being almost as bad as the disease. TRM rates quoted by Khouri for myeloablative allo SCT are in the range of 38-50%. Statistics show approximately roughly 2 out of 3 patients treated with myeloablative allo SCT die either due to TRM, recurring CLL or other complications, but approximately one third will be CURED of their disease. This is a case of 2/3 empty glass and 1/3 full glass.
The aggressive nature of full strength myeloablative conditioning also meant there was very strict age and fitness restrictions placed on who is eligible to go this route. Patients who are young, fit, still in early stage of CLL which is therefore chemosensitive do well with this approach. It gets a little hard to quote firm survival statistics since each institution has its own recipe, its own cocktail of chemo and radiation combinations for the high impact preconditioning and the results vary accordingly. But the bottomline is pretty clear.
Non-myeloablative allogeneic SCT
Now we come to the present day standard of stem cell transplantation technology. Pulling apart the tongue-twisting moniker once again, this too is an allogeneic stem cell transplant, and therefore by definition it involves finding a suitable matched donor willing to donate his / her blood stem cells.
We have already discussed myeloablative approach, heavy handed chemo + radiation combination to eradicate as many CLL cells as possible with an equally impressive treatment related mortality to pay for it.
Non-myeloablative approach takes a slightly lower impact approach to preconditioning. Don’t have any illusions about it, even non-myeloablative approach is pretty strong medicine, it is kinder and gentler only by comparison to its more dangerous myeloablative big brother. Street name for non-myeloablative allogeneic SCT is “mini-allo“. Not so mini, but you get the drift.
Here is the logic of a mini-allo transplant. The preconditioning regimen is used to achieve two goals. One goal is to kill off as many CLL cells as possible in order to reduce the number of the enemy before the new immune system comes in. There is no expectation that every single last CLL cell is eradicated, no attempt to achieve this goal.
The second and equally important goal is to kill of the patient’s own T-cells, NK cells etc, cell lines that are the defense troops whose function is to protect against foreign invaders. Why is this important? Well, if these defenders are still around when the precious new stem cells from the donor come in, they are seen as invaders and promptly killed off. Result is a disaster, the dreaded graft failure. So, it is important that the preconditioning is strong enough to kill host T-cells and the like, to give the new donor cells a chance of surviving.
Most centers still use chemo + radiation (usually lower dose than in myeloablative procedures) in their mini-allo protocols. Since one of the desired goals is to kill host T-cells before transplant, fludarabine is a huge favorite. Ironic, isn’t it – fludarabine’s penchant for killing T-cells that is so dreaded under ‘normal’ therapy conditions is a huge asset in the context of transplant preconditioning. Killing host T-cells is exactly what is needed in order to protect the graft when it is introduced into your body. That is why most transplant centers would prefer if you have had your fair share of fludarabine before you even go to them. That way the transplant team can be assured your T-cells are not frisky and looking for trouble. Even if you have already had fludarabine, almost all transplant protocols will include additional amounts of this important drug to make doubly sure all of your own T-cells are dead and not likely to cause trouble for the graft.
While different transplant centers have their own house blend of chemo + /- radiation recipes for mini-allo preconditioning, you can see that the kinder and gentler mini-allo can only go so far in the department of being kind, a certain amount of bloody murder is needed to make sure your original immune system is truly flat on its back and not likely to put up a fight when the graft comes in. No one wants to risk graft failure.
Graft versus Leukemia
As we mentioned above, the preconditioning in a mini-allo is not expected to eradicate every last CLL in your body, not even close. So how can you expect a cure from this approach? This is where the miracle of GVL (Graft Versus Leukemia) comes in.
You see, a properly working immune system is supposed to hunt and destroy all cancer cells it sees in the body, a case of house to house search & destroy until the last enemy combatant is dead. The reason why you have CLL is because your immune system (mostly T-cells and NK cells) has stopped recognizing the cancer cells as dangerous.
What happens when you throw out the bums, get a new police force in? The newly grafted immune system has no ties to the nepotism of the previous police force and once they are established the new donor T-cells and NK cells go on a dedicated mission of destroying every CLL cell they find. This is the precious GVL effect that is capable of CURING the otherwise incurable CLL. The killing power of allogeneic T-cells and NK cells in destroying CLL cells wherever they hide is far superior to man-made chemotherapy drugs. No such GVL is possible in an autologous transplant since you are getting back your own lazy good for nothing immune system. That is the single biggest reason for the failure of autologous transplants.
M. D. Anderson reported the first results from mini-allo transplants in lymphoid diseases back in 1998. Six years later results from 17 CLL patients who had undergone sibling donor mini-allo transplants were reported by Dr. Khouri’s group. The preconditioning was FC (fludarabine + cyclophosphamide) or FCR (Rituxan was added in the case of patients recruited later in the program). The reduced intensity of the conditioning allowed recruitment of generally older and more heavily pre-treated patients. All patients engrafted and treatment related mortality (TRM) was “only” 22% at 2 years. It is still too high, but a whole lot better than the roughly 38-50% quoted for full bore myeloablative SCT, with the added advantage of younger and fitter patients to boot.
This was pretty impressive stuff, especially since the researchers were able to show significant Graft-versus-Leukemia effect along with the reduced death-due-to-therapy numbers. Much has been learned since those early days, many fine touches added to preconditioning regimens, immune modulation to maximize GVL and minimize graft-versus-host disease (GVHD), better understanding of what constitutes a good match as far as donor selection is concerned, protecting patients from opportunistic infections and the like while their newly grafted immune systems were getting settled down and getting ready to do the heavy lifting. You really need to read the full text article we are reviewing here to get all the interesting tidbits.
So, when is the right time to consider a transplant?
This is perhaps the most important question of all. No one wants to transplant a newly diagnosed patient; SCT is not a valid frontline therapy. On the other hand, should you put off transplant considerations for as long as possible, wait it out till the bitter end and nothing is working before doing a Hail Mary transplant? We discussed some of these issues in our earlier article “Catch-22“. Dr. Khouri gives clear reasoning for his guidance:
“A key lesson learnt .. is that these procedures achieve their best outcomes if they are performed at a stage when the leukemia is still chemosensitive, particularly if the leukemia can be de-bulked to a low disease burden prior to transplantation”.
Makes sense. Since mini allo SCT depends on the fine-tuned effects of GVL to eradicate the cancer and not the heavy handed approach of full strength myeloablative conditioning, it really helps if the ranks of the enemy are reduced ahead of time and the enemy is not a hardened variety that has learned every trick in the book. In other words, if you go in to a transplant in a good remission with very little disease burden and your CLL is still sensitive to chemotherapy, you stand a good chance of coming out a winner. Low TRM because of the reduced intensity conditioning, good GVL because your CLL is still easy to kill, and low risk of CLL relapse because the new graft does not have to face hordes of CLL cells right off the bat – that has all the hallmarks of a successful stem cell transplant.
Dr Khouri further identifies patients who are good transplant candidates, pretty much along the same lines as defined in the formal European consensus on the subject.
- Patients who got only a partial remission after chemoimmunotherapy regimens such as FCR
- Patients who relapsed soon after combos such as FCR
- Patients with 17p deletions
- Any patient who has developed Richter’s transformation
Here is a final quote from Dr. Khouri”
“Patients who relapse following first-line treatment with modern chemoimmunotherapy have a median survival of less than 3 years from the time of relapse, and those patients with the most favorable survival were those who eventually underwent allogeneic SCT. As the process of initiating sibling typing and/or unrelated donor search may take a considerable period of time, we recommend that a discussion regarding the potential need for transplantation be conducted at the time of first relapse from frontline therapy with FCR or equivalent regimen”.
Part Two of this two part article will focus on comparing mini-allo SCT versus standard chemotherapy in a just published 80 patient study. Which group did better? Who lived longer? Coming soon to a website on your computer..
30 comments on "Stem Cell Transplants – Are They Worth It? (Part I)"
Great article! We met in Niagara Falls this January (I was the woman diagnosed at age 24!) I just started CHOP in preparation for a bone marrow transplant this fall. I look forward to the other part of your article. Thanks for your tireless research on my/our behalf.
Sincerely,
Heather
Chaya, just got this!…I started reading it with a little nervousness as I have just committed to a Mini SCT with Dr. Khouri asap (maybe Sept now) after failing a CR on finishing my first treatment of FCR (6 rounds) last fall so I have the same philosphy as he does. I had not heard the 3 year median survial history after failing FCR but I did find some other MDA papers that indicated that maybe I had a 20% chance of being around at 4 years so thanks for bringing this to reality and yea, this is one of those decisions you don’t like to make but you have to make pretty early in your CLL disease. So I looks like Part I is confirming my decision to go forward with Mini SCT now rather than later. I’m really looking forward to Part II!..hope it shows good survival statistics for early SCT since I will be one of the data points on some future paper. Paul
thanks Chaya for this very informative research…..I do hope that in all of the numbers of success, you also managed to get the percentage of post transplanter’s with a good QOL. I talked with Dr. Hosing and the MDACC trnasplant group during the past 3 months about just this subject. The new numbers look amazing, but not so amazing when you dig down to QOL. Even Dr Hosing stated that she has been puzzled as to the serious problems she is seeing with post transplant—(I am talking chronic suffering). I am very proactive about posting ALL the different shades of gray when talking about successful CLL transplants. I don’t care if if was a success if the patient died of another problem due to the transplant. And—that is in the paper’s. Patient 1–no sign of CLL, cured by transplant, died of complications. Let’s all hope that Dr. Khouri filters these successes out of the final MDACC numbers.
Chaya,
Thank you for the valuable information. I am too old, 76 years, for a transplant, but I find this exciting and told with honesty.
I’m still “chuggin” away with chlorambucil. Slowly and I mean slowly my platelets are now 50.
Thank you for all your research on our behalf.
Best Wishes and many Blessings.
Rita
Just to say I am grateful for the no-nonsence tone; as someone who has been treated like an idiot, all the “would not term it cancer, not even leuchemia” etc, and the “this 65-yearold woman”, and, “it probably will not shorten your natural life-span” rubbish! It is terrifying, it is also treated insincerely by the medics, patronising and belittling. Again, thank you, and I am so sorry about your loss. I have three darling daughters and six beautiful grandchildren, three of whom are light brown. Familial scares me ridged! I am Scandinavian myself. Thanks again, Mette
Thanks again Chaya – if it wasnt for you I doubt if we’d get this very important info.
Best Wishes
Lawrence
Hello Chaya,
Very valuable information. These articles really help the lay person both understand and ultimatley decide on different courses of treatment with the help of their medical team.
I am WAW and hope to stay that way for a long time. I had heard or read somewhere that as family donors a female who has given birth has some changes to the stem cells/blood that make the possibility of host vs. graph disease more likely. Wonder if this is common knowledge and if you have heard of this?
God Bless
David
I’m in remission from FCR and hoping it will last forever, but will be waiting for part II with much interest.
Chaya,
Thank you so much for this article. As you’ll recall, I underwent a mini-allo (MUD) transplant on February 4th. “Mini” is a misnomer if I ever heard one. I developed literally every serious trsnsplant complication you can name, including pneumonia in both lungs. I’ll spare you the rest. Six months later, working through some Graft Versus Host issues, I’m finally starting to feel more like myself. What a journey! Can’t wait for part II.
Warmest regards,
bill howard
Chaya:
I tried to find the Cam/Kouri article for the past half hour. Can you help me find it. “Money is no object.”
Thanks, Barry
Chaya,
This was easy to read and understand. Thank You for this kind of writing and choosing important topics for us. You are a strong advocate and ally and I appeciate it. Hope all is going well for you in India.
Chris R.
Chaya, thank you for this objective and timely article. For five years my QOL has been great. However, my remissions have been short; six months for Chlorambucil plus Rituxan and ten months for FCR. I am preparing for a mini allo (MRD)in early September. Looking forward to reading part II. Cindy
I will try to answer some of the questions raised by your comments.
Yes, there were a couple of articles that suggested women donors that have had children are less desirable as donors. The reason is that after childbirth women retain trace amount of the “foreign DNA” of their offspring in their systems for years, even decades. If they become donors they will be donating not just their own DNA but also tiny trace amount of DNA from each of their kids as well, and this might complicate matters. Let me hasten to add this is NOT a huge problem and most centers discount this effect. A well matched donor who happens to be a woman is nothing to sneeze at. Age is a much more important issue. A fit young donor is far preferable to someone who is also getting on in life. Think about it. Many of the immune system cancers such as CLL come later in life. What are the chances your doddering old donor also has some yet unknown but simmering immune system disorder? I would prefer a healthy young man / woman as my donor any day of the week.
Quality of life issues are very important and should be carefully considered. One aspect of post transplant life that can be hard to manage is the dreaded GVHD (graft versus host disease). Now that TRM rates due to preconditioning have been reduced due to non-myeloablative approaches, the next big hurdle is to reduce mortality and morbidity due to GVHD.
I am delighted to tell you this is also the area where most important breakthroughs are being achieved. Part III of this two part article (I spoke too soon) is about a brand new celluar approach to controlling GVHD that I think will greatly benefit patients. This approach is already seeing tremendous benefits in pediatric transplants and fast tracked in adult trials.
Barry, send me a private email and I will help you get the article.
Thanks Chaya for continuing writing such important articles.
I read all about transplants on CLL Topics as well as other places before my Reduced Intensity SCT in March.
We often hear about those that the journey was bumpy and a lot of fear is built up, however there are also good journeys.
I am now 4 months post transplant and at times I think the whole thing was a dream or a fixture of my imagination. I have not had a bumpy journey so far, and although the transplant consultant team has said it is my attitude no that I have not had it hard, I still feel if I had to do it all over again, I would without thinking twice about it.
I think being well prepared for everything and trusting the Transplant Consultant Team, makes the journey safer and more relaxing.
Everything that happened was expected and they dealt with it prompt.
Lately I have been interested in the different pre-conditioning protocols used by Transplant Centres, and the reasons they use them.
chonette
Chaya,
Why are there “few good choices” once the remission ends following an autologous SCT? I would have thought that an auto SCT would put one back into early watch and wait mode with the same chemo choices as before.
Thanks for the article,
Tim
I am presently 20 months post-transplant after a mini-allo transplant in November, 2007. I just completed my bi-annual check-up (with bone marrow analysis) and, at present, show no signs of recurrence. Although the article Chaya discusses is important, it doesn’t say a lot about what it is like to live through a SCT as a patient. If my personal experience can be of use, here is a summary:
I was diagnosed with CLL in November, 2006 at age 57 (in relatively healthy shape otherwise). Although I caught the CLL early, the prognostic markers did not look good. I had a 17p- & 11q- chromosonal abnormalities. I was positive for ZAP-70 and CD38. I was showing significant adenopathy. My WBC was 26,000. When my WBC topped 50,000, in June, 2007, I was started on FCR at my local oncologist’s clinic in Florida. I failed to respond to my initial course of FCR. A lymph node biopsy showed Richter’s Transformation. I was immediately went to a major SCT center in the first week of August, 2007. (One week after the lymph biopsy.) At the SCT center it was strongly recommended I have a SCT and NOT try anymore chemotherapy. (This was a shock since, even in 2006, I thought a SCT was the last resort. My wife and I made this decision, over the phone, in an hour.) Before I left the SCT center in August I met with the pre-transplant team, including my transplant doctor.
At lot of luck then came into play. Because I had three siblings, it only took one month to find out I had a donor. One of my sisters was a perfect match. While we were testing my sisters it only took four weeks for my insurance company to approve the SCT. (So by mid-September I had a donor and insurance coverage.) The SCT center was able to take me as soon as I could get there. By October, 2007, my wife and I had rented a furnished apartment in the city where the SCT center was located for the procedure and moved into it. On October 10th, I showed up at the hospital for two weeks of tests and preparation (e.g. blood tests, infectious disease screen, central line, bone marrow, CTs, eye exams, pulmonary tests, etc.) During those two weeks my sister arrived and donated her stem cells. Once my transplant doctor knew we had enough stem cells collected to do the transplant, I was started on a two week conditioning regimen of chemo and full lymph radiation. I was in-patient for the first week of the chemo and radiation conditioning treatment. On the last day of my radiation (Nov. 7, 2007) I was transplanted with my sister’s bone marrow (a four hour infusion) and, because of the protocol I was on and my relative health, my wife took me back to our apartment for dinner and then, at last, bed. (This was a big surprise also since I thought I was going to be inpatient for at least another 30-45 days.
I was fortunate enough to complete the entire post-transplant procedure as an outpatient. For the first 60 days I went back to the hospital every single day (yes, including Thanksgiving and Christmas) for blood tests and infusions. At Day 100 (transplant day is Day 0) I was released to go back home to Florida. Other than some moderate chronic GVHD I had no other complications with the transplant. The first 100 days, and the ensuing 3-4 months, were not easy. I lost interest in food and lost weight (despite a loving wife who was constantly bringing me snacks!), I was always tired, I lost strength,I slept 10-12 hours a day (thank goodness for naps, I still take them), I was unable to go back to work, and, for obvious reasons, wore a mask when I went out in public (which was not often).
I was required to come back to the SCT center every three months for the first year after I was released for tests. I now have to go back to the SCT center every 6 months.
When I returned home to Florida the SCT center prepared a complete package for my local oncologist and my follow up care at home was great. I had blood tests every 2 weeks for the first 6 months after being home. Now I only see my local oncologist every 2 months.
At 20 months post transplant I am probably as near “normal” as I am going to get. I am back to normal sleeping, eating, working, and exercising. (I still sneak a nap when I can get it.) I even went two months without seeing any doctor, at all, for anything! I have had some mild GVHD problems (skin) which were managed by increased immunosuppressants and topical creams. As warned by the SCT center, I have to be careful about the sun and pre-cancerous skin lesions (A dermatologist is part of my local care team.) I am still on a low dose of immunosuppressants and associated prophylactic drugs (anti-viral, anti-bacterial, anti-fungal). If I am still negative for CLL in six months I will probably be taken off the immunosuppressants all together.
If I had to pick out important turning points in my story, the first would be, after failing to respond to the initial round of FCR-chemo, deciding to go to a SCT center and see a doctor familiar with ALL of the issues described in this article and CLL-Richter’s Transformation. The second would be having a sibling who was a perfect match (OK, I owe her big time, right?.) The third would be my relatively high chemosensitivity (after only two courses of FCR) and being able to significantly debulk the disease prior to the transplant. The fourth was being able to have the transplant as an outpatient. (I sure didn’t feel well for the first two months and I spent most of the days at the hospital anyway, but knowing every night my wife would take me back to our apartment was a BIG psychological boost. I felt like I still had some control of my life, albeit I wasn’t exactly out dancing at night.) Fifth, I educated myself on immunobiology, CLL and SCT’s to the point where I could have intelligible discussions with all of my doctors on almost any subject. And, finally, choosing a local oncologist who is extremely competent and was willing to do anything to get me the care I needed when it was clear the “usual treatment” (FCR) wasn’t going to work.
Sorry for the long post! As in anyone’s story, I left a lot out, some of it will only apply to a handful of people, but I hope it might be useful for some.
tworrall:
Autologous stem cell traansplant is no more than glorified high impact chemotherapy +/- radiation, followed by infusion of the patient’s own stem cells harvested earlier. Severl issues with this approach for patients who have relapsed shortly after completion of FCR. First, unless stem cells have been collected much earlier (soon after diagnosis and initiation of therapy), stem cell harvesting is very difficult in relapsed patients. Second, patients who have relapsed soon after FCR do not respond well to additional chemotherapy, including auto SCT preconditioning. The remissions are miserably shallow and short.
And no, I doubt any expert would tell you to expect to roll the disease back to early stage W&W with the same choices as before. FCR relapse burns a lot of bridges.
Spike:
Thanks for responding to my request and telling your story. All too often SCT is painted in the darkest colors. One expert actually said those who are alive after SCT often wish they were not. That is very negative and out of touch with the much improved protocols (especially the non-myeloablative preconditioning). As you pointed out, SCT decisions are not easy and must be taken seriously with informed discussion between patient, family and the transplant team. But as in your case, it is possible to return to normal life, more or less. Sans transplant and after a Richter’s transformation I doubt you would have been able to post the comment above.
When you are at the end of the usual therapeutic options, deciding to have a transplant may be easy, but it is way less likely to be of much help.
Electing to have a mini transplants earlier is always a difficult decision. You move your risk of mortality (20% or more if you have any other risks factors) and morbidity (100% but not always severe or ling lasting) upfront for about a 50/50 chance at a cure. You trade a nearly 100% chance of living out the next few years for a 20% of dying soon and only 1/2 a chance for a cure. But that’s way better than no chance.
The deeper the remission before transplant, the lower the risk of relapse. If remissions come easy, hold off. If your first was short lived, or difficult to achieve, your second may be your best chance, and you might not want to wait too long to get your ducks in a row, especially if you are one of the increasing numbers of young CLLers.
You trade a safe present for a chance at a long future. For me the choice was easy. My blog, especially the very early postings goes into more detail -bkoffman.blogspot.com
I’m 35 years old and was diagnosed with CLL/SLL (doctors use the terms interchangeably) aged 30. I had chlorambucil (no real remission – just a temporary regression of the disease) and then FCM on the UK CLL01 trial, which produced what my consultant termed an ‘almost complete response’. I have been in remission for almost 2 years now, during which time my wife and I took time out from work and travelled the world for 6 months. Serious diseases do change one’s perspective!
I now have some small granular nodes reappearing in my neck, so I am beginning to think that I am on my way out of remission. I have an older sister (39) who is a 10-point match for me and willing to donate (I am very lucky in that respect). SCT seems to be in my future, but so are kids… My wife and I are expecting twins in December. It was a tough decision to try for kids, but we decided to go for it after much deliberation. That was not easy either, as FCR had rendered me almost fee of CLL, but completely free of sperm! We had stored some pre-chemo and were able to get IUI and got lucky first time.
Of course, all of this does not make the decision of if/when to go for and SCT any easier.
One thing that strikes me is that if I manage to make it through the SCT, I hear little about the details of living with the complications of it. I know that GVHD is common and have read that it can affect the mouth, GI tract and skin, but what exactly are the typical symptoms and what is the likelihood and severity of them?
Pehaps forum members with personal experience could comment?
I really like hearing from people like Spike who tell their personal stories. I personally would like to hear more about what Spike went through as this was a consiced story.
Chaya thanks for all the information. I am a better informed CLL patient because you tell it like it is.
Wish you the best on your trip.
Mocha said:
August 10th, 2009 at 9:45 am
“I really like hearing from people like Spike who tell their personal stories. I personally would like to hear more about what Spike went through as this was a consiced story.”
For those not familiar with the process I’ve blogged ours. It is covered here:
http://ackjackie.blogspot.com/
This is a response to Bill Spence’s concern about GVHD. You have to separate acute from chronic GVHD. (Acute GVHD occurs during the first 90 days after transplant.) It is true that GVHD can be severe and life threatening, however with good donor match GVHD is usually mild to moderate. Also keep in mind your transplant doctor will actually want you to have a “little” GVHD. (Survival rates are higher for patients who exhibit GVHD. It seems GVL & GVHD are linked.) The SCT centers are also getting MUCH better at heading off severe reactions of GVHD with various drug combinations (e.g. ATG prior to transplant, methotrexate after).
I only had a mild rash in the first 90 days (acute GVHD) after transplant. I talked to many of my fellow transplant patients and a lot of them had chronic GVHD, but usually only moderate skin and/or mouth symptoms. Some people had none whatsoever. I only knew three fellow patients who had moderate to severe acute GVHD where it attacked their intestines and/or esophogus. My transplant doctor had me on two different kinds of immunosuppressants, Cellcept and Prograf, which worked very well. (But your immune system is wide open to infection when you are immunosuppressed, so be aware and wise.) Also remember at most SCT centers you will either be inpatient or you will be scheduled into a transplant clinic almost every day for the first 30-60 days. You will see a transplant nurse EVERY day and he or she will look specifically for any symptoms of GVHD. Also, when I was discharged, my SCT center wrote a long, detailed letter to my local oncologist on what to look for, how to treat it, and to contact the SCT center if there were any problems.
I did develop chronic GVHD at about day 130. It was basically a rash and/or redness (sunburn) on the upper third of my body. The GVHD-affected skin was very tender. Having chronic GVHD was annoying, uncomfortable, and frustrating, but it didn’t stop me from doing things I was able to do. I used a steroid cream to help counteract the GVHD along with maintaining immunosuppressants. (If you develop mouth GVHD the doctors will give you a steroid mouthwash to use.) The worst symptoms of my GVHD only lasted 2 months, with another 8 months of milder symptoms. I am slowly tapering off immunosuppressants (I am off Prograf, only on a low dose of Cellcept at 20 months.) I have not had any GVHD symptoms for 6 months.
A SCT is an unknown. And it is a miracle. I am grateful every day for getting one, and getting it early. Each of our bodies is complex, complications will arise, but at no time since the transplant have I ever wished I had NOT had the SCT. A SCT doesn’t take away all of life’s problems, only one very big one.
Wow!
Great measurable criteria Chaya on when to make that tough choice and loved all the stories of life after SCT. Quality of life is so important and in my case with 2 year old twins, absolutely critical. Thanks Spike for all the life after SCT stories. Would love to hear more after SCT from others.
Thanks Chaya for your efforts. Looking forward to your usual informative updates.
Leo
Chaya,
Thank you so much for your informative srticle! Question…if one third of patients can potentially expect to be cured, why do some insurance companies consider SCT for CLL experimental? Is this a valid positon on their part?
Leslie
Leslie:
Insurance companies are in the business of making money. Stem cell transplants are very expensive, ranging anywhere from half a million dollars to several million dollars depending on the level of complexity of the particular case. You figure out why they would like to consider SCT an experimental procedure and therefore not covered by their policy, for as long as they can get away with it.
But it must also be stated that SCT protocols are changing rapidly as we come up the learning curve. While the general parameters are well established and no medical expert would call SCT to treat CLL “experimental” any more, it is still a work in progress. I do not think that gives insurance companies the right to refuse coverage and infact many of the major insurance companies do cover it. I know Aetna does, it was our policy holder and it covered my husband’s cord blood stem cell transplant.
Chaya,
Thanks for your response on insurance coverage of SCT. I checked with Blue Cross and Blue Shield of MA (our carrier) today (I had checked about 3 years ago) and they said that they do not cover SCT because it hasn’t been proven to be of greater benefit compared to standard treatment.
Chaya,
Thank you for another great article.
I am on Day 138 following a mini allo SCT. Everything I have read in your article has confirmed that it was absolutely right for me to decide to have the SCT.
My story is that I am a 55 year old male diagnosed in September 2007. I had bad markers with CD38 at 98% and also 11q. I started 6 rounds of FCR in August 2008. It was only as I went through FCR that I began to decide to go for SCT straight after first remission. Some of my reasons were: I was young (ish), I was in good health, I had bad markers, the cumulative effect of FCR got to me, and I had a good sibling match. But probably the deciding factors for me was that I was a) 11q and b) I am a person who likes to be in control (or so my wife keeps telling me) and I could not let this invader control my life, I had to go out and actively fight it.
Did I find it difficult? Yes absolutely. I spent nearly 7 weeks in hospital and another 3 living close by before I could move back home. I could not eat any solid food from about Day -2 to about Day 24. But put in the exact same situation I would have no hesitation is doing it again.
However, I have had no GVHD. Not one rash or mouth sore of any kind. In addition I have been completely infection free. On Day 88 I got the results of the chimerism test which showed my sisters stem cells had 99% engrafted. On Day 103 I was taken off anti rejection drugs completely. As yet I have not the complete all clear as I am waiting on the results of a recent chimerism test. However my CT scan was normal (having originally had very bulky nodes). My only complaint is that I suffer intermittently from bad fatigue which seems to come out of nowhere and lasts for few hours or days. But then other times I feel absolutely fine.
Chaya, perhaps you could comment on the remark earlier by Spike that GVL and GVHD are linked and a “little” GVHD is good.
I also have failed to find the Khouri article. I will send you a private email as you suggested to Barry.
Thanks again for all you do for CLL’ers all over the world.
Clum
Clum:
Part three of this series will be all about GVHD. I think it will answer your question about why a little GVHD is good.
Chaya,
Your selfless devotion and your profound insights have no peer in this realm of CLL, we thank you, thank you and thank you again!
What is a mystery to me is all of the above patients do not mention the effects of your article GVHD: Graft Verses Host Disease ; “Let them eat yogurt.” Perhaps the article has not been read by some, so I enclose here a testimonial of my experience in this regard:
After Treatment of Chemo
If you are like me after your treatment with chemo your stomach and Gastro Intestinal Tract (GI) is uncomfortable to say the least.
A major effect of complications after chemo is the inflamed tissue due to the fact that the mucus membrane lining is sloughed off the GI, as the doctors put it. The mucus membrane protects us from foreign bacteria and virus, once sloughed off there is no protection and inflammation immediately is the result leaving this tissue susceptible to invasion of bacteria and viruses.
Your oncologist will prescribe antibiotics and anti viral drugs as a prophylactic to guard against foreign bugs. If you take these drugs there will be side effects which in part will be the difficulty of becoming resistant to these drugs thus making it necessary to take stronger antibiotics and anti viral meds when actually needed.
There is a study “GVHD” on CLLtopics.org which shows that the mucus can be reestablished very quickly using a human friendly bacteria known as Lactobacillus Ramosus GG (LBR).
Recently I have had another series of chemo with the resulting mucus sloughing problem, I did not use the prescribed prophylactic drugs but used the LBR. Within 10 hours of taking the LBR cultivated into a yogurt my GI settled down and within 24 hours my normal regularity returned. It has been one week now and all discomfort has vanished.
You cannot take the antibiotics and LBR together as the antibiotic will cancel the effect of the LBR.
If you are interested in using LBR you will need a large dosage of the product in its capsule form. You may wish to cultivate the LBR by making it into a tasty yogurt. If you wish to do this it will be less costly then taking large amounts of the commercially prepared LBR and in my case I feel yogurt is more effective.
You may purchase a yogurt maker and use the instructions provided with the maker, your “Starter” will be the LBR one capsule per 8 oz. container, cut open the capsule and mix it into the warm milk. I use organic reduced fat Horizon brand milk (no hormones, antibiotics) along with one heaping teaspoon of Meyenberrg brand powdered goat milk per 8 oz cup which gives a creamy and tasty effect. Do not add any sugars, fruits etc.
I take one eight oz of this yogurt twice a day. You may use this prepared yogurt as a starter for the next batch for about five times or more.
The source for the LBR is, get this, Wal Mart! It is sold under the name Culturelle Probiotic
company telephone # 1-800-722-3476 if you cannot find it there.
As a side bar I have never had any nausea associated with chemotherapy, nor diarrhea or any of the other side effects other then low blood counts, fatigue and hair loss. Therefore I cannot attest to the efficacy of LBR in relieving nausea but I would like to know if any of you who have had nausea and diarrhea after chemo and who are taking the LBR find that these side effects of chemo have ceased or at least been effected in positive way after using LBR.
Be well,
Roger Worldie
email: designfab@earthlink.net
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