After an autologous stem cell transplant, what percentage of your immune function can you hope will be restored? Since the transplant basically wipes out your immune system, should you expect to have some level of immune impairment for life, or do some people recover with minimal impairment (at least until their myeloma relapses)?.
I've always had a great immune system, and I have this wishful thought that my good immune system will regrow since it's in my stem cells. (This is only my wishful thinking though).
And how long does it take for the immune system to 'grow back', assuming the transplant works as intended, and you get at least 'a few years' of no myeloma?
Thanks
RT
Forums
-
RadiantTiger - Name: Radiant Tiger
- Who do you know with myeloma?: Myself, my deceased uncle
- When were you/they diagnosed?: Feb 2015
- Age at diagnosis: 54
Re: Immune system recovery after transplant?
Hey Radiant Tiger,
So, there are a couple of scenarios to consider here.
One is the reconstitution of your immune system assuming that the myeloma is completely wiped out by the high-dose (HD) chemo (melphalan) and it is not reoccurring and/or interfering with your immune system post-auto-transplant.
And then you've got the other situation, where the HD chemo isn't successful, or is only partially successful, and the multiple myeloma is interfering with your immune system recovery post-auto-transplant.
I think your question is around the first scenario. Basically, there are many different components to one's immune system that are reconstituted and come back "online" over a period of time. Some parts of your immune apparatus come back online in weeks. Other parts of the immune system are restored over a period of months. With some other parts of your immune system, it could be well over a year or more before they are fully back up and operational again, provided there isn't any interference from the multiple myeloma. In any case, many of your earlier disease immunities are largely wiped out by the HD chemo / transplant process. This is why you have to get re-vaccinated after receiving a transplant.
So, I think the answer is that, if all goes well, you can expect your immune apparatus to be pretty close to normal after a year or two, provided the multiple myeloma hasn't come back. Having said that, some people take the transplant process in stride, are back in the saddle again in a matter of weeks (even though their immune systems aren't completely restored, they are healthy and do just fine without any special precautions) and do quite well for many years. Others don't fare quite as well and never fully recover from the transplant procedure and remain immunocompromised to some degree, sometimes finding themselves in a worse position than before they had the transplant. And others have transplants that pretty much fail right out of the starting gate and are back to square one shortly after the transplant. Such is the nature and risk of auto transplants and multiple myeloma treatments in general.
So, there are a couple of scenarios to consider here.
One is the reconstitution of your immune system assuming that the myeloma is completely wiped out by the high-dose (HD) chemo (melphalan) and it is not reoccurring and/or interfering with your immune system post-auto-transplant.
And then you've got the other situation, where the HD chemo isn't successful, or is only partially successful, and the multiple myeloma is interfering with your immune system recovery post-auto-transplant.
I think your question is around the first scenario. Basically, there are many different components to one's immune system that are reconstituted and come back "online" over a period of time. Some parts of your immune apparatus come back online in weeks. Other parts of the immune system are restored over a period of months. With some other parts of your immune system, it could be well over a year or more before they are fully back up and operational again, provided there isn't any interference from the multiple myeloma. In any case, many of your earlier disease immunities are largely wiped out by the HD chemo / transplant process. This is why you have to get re-vaccinated after receiving a transplant.
So, I think the answer is that, if all goes well, you can expect your immune apparatus to be pretty close to normal after a year or two, provided the multiple myeloma hasn't come back. Having said that, some people take the transplant process in stride, are back in the saddle again in a matter of weeks (even though their immune systems aren't completely restored, they are healthy and do just fine without any special precautions) and do quite well for many years. Others don't fare quite as well and never fully recover from the transplant procedure and remain immunocompromised to some degree, sometimes finding themselves in a worse position than before they had the transplant. And others have transplants that pretty much fail right out of the starting gate and are back to square one shortly after the transplant. Such is the nature and risk of auto transplants and multiple myeloma treatments in general.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Immune system recovery after transplant?
So, I think the answer is that if all goes well that you can expect your immune apparatus to be pretty close to normal after a year or two, provided the multiple myeloma hasn't come back.
Well that would make it worth the shot then.
Having said that, some people take the transplant process in stride, are back in the saddle again in a matter of weeks (even though their immune systems aren't completely restored, they are healthy and do just fine without any special precautions) and do quite well for many years. Others don't fare quite as well and never fully recover from the transplant procedure and remain immunocompromised to some degree, sometimes finding themselves in a worse position than before they had the transplant. And others have transplants that pretty much fail right out of the starting gate and are back to square one shortly after the transplant. Such is the nature and risk of auto transplants and multiple myeloma treatments in general.
Yep, no guarantees at all. So, is 18 months still the 'average time to relapse' after transplant? (I think I read that somewhere). That's not very long. Are there any particular indicators that would put your odds beyond 18 months, like having a 'CR' response to induction treatment, or some such thing?
Thanks Multibilly.
RT
-
RadiantTiger - Name: Radiant Tiger
- Who do you know with myeloma?: Myself, my deceased uncle
- When were you/they diagnosed?: Feb 2015
- Age at diagnosis: 54
Re: Immune system recovery after transplant?
RT,
I will leave it to others on the forum to speak to the topic of average time-to-relapse and factors that can impact time-to-relapse and overall survival.
Regarding your induction response question as it relates to SCTs, there was some very surprising (at least to me) recent data that suggested that the depth of induction response didn't correlate with OS post-transplant:
"Additional Treatment To Deepen Response Prior To Transplantation May Not Improve Survival In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, March 23, 2015.
I will leave it to others on the forum to speak to the topic of average time-to-relapse and factors that can impact time-to-relapse and overall survival.
Regarding your induction response question as it relates to SCTs, there was some very surprising (at least to me) recent data that suggested that the depth of induction response didn't correlate with OS post-transplant:
"Additional Treatment To Deepen Response Prior To Transplantation May Not Improve Survival In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, March 23, 2015.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Immune system recovery after transplant?
I just want to add a modifier to what Multibilly posted about being revaccinated following a transplant. Not all of the cancer centers recommend revaccination. I asked my oncologist about it after my transplant. He, and his team, don't recommend it. They are of the belief that, since we receive our own stem cells in the transplant, our immunity is preserved.
I had asked him about it because I worked in a health care setting in direct patient care, and we were required to be immunized against certain diseases. I never had my titers done to see if I still had immunity to anything. But, except for the first year post transplant, I haven't been sick at any time.
If you are concerned, I would suggest that, after a year post transplant, you ask either your oncologist or your primary doctor to order titers for the things that we are normally vaccinated for. That way, you will have some guidance as to whether you want to go ahead and get revaccinated or not.
Nancy In Phila
I had asked him about it because I worked in a health care setting in direct patient care, and we were required to be immunized against certain diseases. I never had my titers done to see if I still had immunity to anything. But, except for the first year post transplant, I haven't been sick at any time.
If you are concerned, I would suggest that, after a year post transplant, you ask either your oncologist or your primary doctor to order titers for the things that we are normally vaccinated for. That way, you will have some guidance as to whether you want to go ahead and get revaccinated or not.
Nancy In Phila
-
NStewart - Name: Nancy Stewart
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 3/08
- Age at diagnosis: 60
Re: Immune system recovery after transplant?
All myeloma patients have a dysfunctional immune system at diagnosis. A patient would not have myeloma if they had a healthy functioning immune system.
Myeloma patients start with a dysfunctional immune system and it gets furthered impaired due to the therapies used.
Outside of allo transplant, a small group of patients that do autos appear to have immune systems that reconstitute and help keep the myeloma in check long term. These patients were treated before maintenance therapy was common.
Myeloma-related innate immunodeficiency involves various arms of the immune system and includes B cell dysfunction (manifested as hypogammaglobulinemia), numerical and functional abnormalities of dendritic cells [3] and T cells (inversion of CD4:CD8 ratio [4], abnormal Th1/Th2 CD4+ratio [5], and severe disruption of global T cell diversity [39]), and dysfunction of natural killer cells [40]."
Source: M Nucci and E Anaissie, "Infections in Patients with Multiple Myeloma in the Era of High-Dose Therapy and Novel Agents," Clinical Infectious Diseases, 2009 (link to full text of article)
Myeloma patients start with a dysfunctional immune system and it gets furthered impaired due to the therapies used.
Moreover, the prolonged survival resulting from novel therapies has transformed myeloma into a chronic condition [49], with multiple relapses and salvage therapies, all of which result in cumulative immunosuppression and higher risk for infection. Indeed, levels of CD4+T cells, particularly naive and activated subsets, decrease significantly with increasing cycles of chemotherapy, a decrease strongly associated with opportunistic infections [50]."
"Compared with therapy with oral melphalan plus prednisone-based regimens, current therapies (autologous and allogeneic HCT and the novel agents thalidomide, lenalidomide, and bortezomib) have improved the outcomes of patients with myeloma [49]. These therapies impact the immune system differently [14], and their application has resulted in the emergence of infections not previously associated with myeloma, such as those caused by cytomegalovirus (CMV) [15], Aspergillus species [53], Fusarium species [54], herpes simplex virus (HSV), and varicella-zoster virus (VZV) [26], the prevalence of the latter 2 significantly increased following treatment with bortezomib [55] (Table 1) [13–15, 20–22, 26, 56–62]. Although the newer agents are relatively well tolerated, their use has resulted in additional complications that may predispose recipients to infection, such as deep venous thrombosis (thalidomide, lenalidomide) and peripheral neuropathies (thalidomide, lenalidomide, and bortezomib) [25]."
Outside of allo transplant, a small group of patients that do autos appear to have immune systems that reconstitute and help keep the myeloma in check long term. These patients were treated before maintenance therapy was common.
With the introduction of high dose therapy / autologous stem cell transplantation as well as novel agents (up-front), most patients with multiple myeloma (multiple myeloma) achieve a transient remission; however, the vast majority relapse within a median of 3 years from diagnosis.1 Thus, long-term follow-up studies in the setting of high dose therapy/ autologous stem cell transplantation show that only a small fraction of multiple myeloma patients (6-18%) remain relapse free for 10 years or more, and these patients are now considered as being operationally cured.2-4 Interestingly, this operational cure is not restricted to patients in complete response, since those who revert to having a monoclonal gammopathy of undetermined significance (MGUS)-like profile may also achieve long-term disease control (LTDC), despite persistence of a residual M-component.4 Recent clinical and molecular data suggest that some features may help to identify this group of LTDC-MM patients such as an evolving smoldering pattern, a gene expression profile signature of MGUS and the CD2 molecular subtype.5,6 Collectively, these findings suggest that in addition to antimyeloma therapy, other factors may play a critical role in disease control."
"Since patients who are relapse-free for ≥10 years are considered to be operationally cured,4 we further investigated the immune profile of this specific subgroup of LTDC-MM patients. Interestingly, these patients had significantly increased numbers of CD8+ and CD4+ T cells, naïve B cells and m-DC, not only compared to LTDC-MM patients with 5-10 years follow-up, but also compared to healthy adults. These findings suggest that the immune profile of LTDC-MM patients does not reflect a simple overall recovered immune status identical to that of healthy adults of similar age, but rather an unique “immune signature”.
In summary, our results indicate that LTDC-MM patients have a constellation of unique immune changes, consisting of increased numbers of effector cytotoxic CD8+ T-lymphocytes and NK cells, B cells, normal plasma cells and also DC, with simultaneous reduction in Treg cells potentially favoring both the action of cytotoxic cells, and the recovery of B-cell production and homing of normal plasma cells into the BM. Altogether, these unique features of patients with LTDC-MM suggest that the
patients have improved immune surveillance, which deserves further investigations to dissect the specific underlying molecular and functional mechanisms involved."
Source: RJ Pessoa de Magalhães et al, "Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry," Haematologica, Jan 2013 (link to full text of article)
Related Beacon news article: "Research Sheds Light On The Immune System Of Multiple Myeloma Patients With Long-Term Disease Control," The Myeloma Beacon, Aug 30, 2012.
-
Mark11
Re: Immune system recovery after transplant?
Mark 11, this paper which you so eloquently quote in parts only serves yet again to highlight the complexity of multiple myeloma and its heterogeneity in terms of response to treatments and the outcomes in terms of disease control and the factors at play in the immune system. Multiple myeloma is a disorder of the immune system at its root, That is what an immunology trained research onco-haematologist said to me.
The study looks at only 74 patients in one country. It would be helpful to have a more extensive study including results from other centres. The fact that treatment protocols can be so variable in different countries may make replication difficult. So this kind of study would benefit from an equivalent of a multi-centre international clinical trial to draw definitive conclusions.
Edna
The study looks at only 74 patients in one country. It would be helpful to have a more extensive study including results from other centres. The fact that treatment protocols can be so variable in different countries may make replication difficult. So this kind of study would benefit from an equivalent of a multi-centre international clinical trial to draw definitive conclusions.
Edna
Re: Immune system recovery after transplant?
Regarding Nancy's comment that concluded with:
Good point Nancy. Getting one's titers re-checked before just going out and getting revaccinated seems like a good way to first approach the problem and maybe everyone doesn't need to get revaccinated. I stand corrected.
If you are concerned, I would suggest that, after a year post transplant, you ask either your oncologist or your primary doctor to order titers for the things that we are normally vaccinated for. That way, you will have some guidance as to whether you want to go ahead and get revaccinated or not."
Good point Nancy. Getting one's titers re-checked before just going out and getting revaccinated seems like a good way to first approach the problem and maybe everyone doesn't need to get revaccinated. I stand corrected.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Immune system recovery after transplant?
Vaccines are recommended for patients who have had autologous or allogeneic stem cell transplants (see, for example, this CDC statement on the subject). I did receive many vaccines, including DPT, iv, measles, mumps, rubella, hepatitis B, influenza, HibB, meningococcal, pnueumococcal. I still take a 'flu' shot every year too.
In order to get revaccinated, I needed to be referred to the public health clinic from the bone marrow transplant unit. I was healthy enough at the time to be recommended to get vaccines.
Whether or not I am fully protected now against those diseases is sort of a moot point, since I haven't had titres done. However, I haven't contracted any serious illnesses since my transplant 5 years ago, and there are diseases circulating, such as measles, that one would want to be protected against.
Hope that helps. It's not a scientific response as to how well one's immune system recovers, but those are guidelines to follow.
In order to get revaccinated, I needed to be referred to the public health clinic from the bone marrow transplant unit. I was healthy enough at the time to be recommended to get vaccines.
Whether or not I am fully protected now against those diseases is sort of a moot point, since I haven't had titres done. However, I haven't contracted any serious illnesses since my transplant 5 years ago, and there are diseases circulating, such as measles, that one would want to be protected against.
Hope that helps. It's not a scientific response as to how well one's immune system recovers, but those are guidelines to follow.
-
Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Immune system recovery after transplant?
Hi Mark,
Don't you think it's an oversimplification to state that:
I mean, it's a truism that a myeloma patient's immune system is dysfunctional, because plasma cells are part of the immune system. So having malignant plasma cells by definition means that your immune system is dysfunctional.
If that's all your saying, then, sure, I'll agree with that.
But I think you're saying something different, which is that, if myeloma patients had a normal, healthy immune system other than their malignant plasma cells, then they would be able to fend off and suppress the myeloma cells, and thus not get myeloma.
And I'm not sure that's really true.
You and others here can correct me if I'm wrong about this. But I think the model most myeloma researchers carry around in their heads about how myeloma develops is that mutations occur "somewhere" (exactly where is a subject of debate) that yield plasma cells that can resist even a healthy immune system's attempts to suppress the expansion of the malignant plasma cell clone.
Or, as the authors of one research paper put it, "myeloma arises as a consequence of the deranged biological behavior of a plasma cell that has undergone a complex development process." (EM Boyle et al, "Understanding The Multiple Biological Aspects Leading To Myeloma," Haematologica, April, 2014 [link to full text of article])
Mutated plasma cells are probably developing in all people, healthy and otherwise, but certain ones are sufficiently crafty that they can overwhelm even healthy immune systems.
If a healthy immune system is all that one needs to overcome myeloma, then why is it that even allo transplant patients who achieve 100 percent chimerism – meaning they now have the immune system of their donor (who doesn't have myeloma) – often relapse?
Don't you think it's an oversimplification to state that:
All myeloma patients have a dysfunctional immune system at diagnosis. A patient would not have myeloma if they had a healthy functioning immune system."
I mean, it's a truism that a myeloma patient's immune system is dysfunctional, because plasma cells are part of the immune system. So having malignant plasma cells by definition means that your immune system is dysfunctional.
If that's all your saying, then, sure, I'll agree with that.
But I think you're saying something different, which is that, if myeloma patients had a normal, healthy immune system other than their malignant plasma cells, then they would be able to fend off and suppress the myeloma cells, and thus not get myeloma.
And I'm not sure that's really true.
You and others here can correct me if I'm wrong about this. But I think the model most myeloma researchers carry around in their heads about how myeloma develops is that mutations occur "somewhere" (exactly where is a subject of debate) that yield plasma cells that can resist even a healthy immune system's attempts to suppress the expansion of the malignant plasma cell clone.
Or, as the authors of one research paper put it, "myeloma arises as a consequence of the deranged biological behavior of a plasma cell that has undergone a complex development process." (EM Boyle et al, "Understanding The Multiple Biological Aspects Leading To Myeloma," Haematologica, April, 2014 [link to full text of article])
Mutated plasma cells are probably developing in all people, healthy and otherwise, but certain ones are sufficiently crafty that they can overwhelm even healthy immune systems.
If a healthy immune system is all that one needs to overcome myeloma, then why is it that even allo transplant patients who achieve 100 percent chimerism – meaning they now have the immune system of their donor (who doesn't have myeloma) – often relapse?
Last edited by Cheryl G on Tue Apr 14, 2015 6:55 pm, edited 1 time in total.
22 posts
• Page 1 of 3 • 1, 2, 3
Return to Treatments & Side Effects