[Mark]

Re: When do you do SCT?

by Mark on Sat May 26, 2012 3:25 pm

NancyStLou,

I hope all is well with you. I was also diagnosed with Myeloma in my 40's. It sounds like you and I have the exact opposite presentations of Myeloma. Mine came on suddenly and it was aggressive. I did an Allo as soon as I got in my first CR. I am a little over a year out from my Allo and I am very glad I did it. I got a Molecular Response and my QOL is outstanding. I have no therapy related side effects at the moment.

Just a couple of things to remember when considering an Allo. With an Auto it does not appear that it matters if it is done early in disease course or if it is done at relapse - the Overall Survival of patients is similar with either strategy. An Auto transplant is a high dose of drugs, nothing more. An Allo is a real transplant that is a more complex procedure. A study at 2011 ASH clearly showed how much better an Allo can work when done as part of planned, upfront therapy.
https://ash.confex.com/ash/2011/webprogram/Paper37067.html

A negative risk factor for Allo transplant is relapse off of prior Auto(s).
"In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16–6.74; P = .02), relapse (HR, 4.14; 95% CI, 2.04–8.38; P < .001), event-free survival (HR, 3.11; 95% CI, 1.77–5.46; P < .001), and overall survival (HR, 2.69; 95% CI, 1.35–5.35; P = .005)."
http://www.bbmt.org/article/S1083-8791(04)00272-1/fulltext

"In multivariable analysis of patients receiving only non-myeloablative transplants, decreased overall survival and PFS were associated with relapse after a prior autograft and a β2 microglobulin >4.0. Transplant mortality was reduced and only influenced by a prior tandem autograft."
http://www.ncbi.nlm.nih.gov/pubmed/22327126

If an Allo transplant is something you would consider in the future, that may influence if you do an Auto early. I am a big believer in doing a doing a partially T Cell depleted Allo for long term quality of life considerations. This is a study on various blood cancer patients with respect to partially T Cell depleted Allos. HRQL is health related quality of life
.
“Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms.”
“These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL.”
http://www.ncbi.nlm.nih.gov/pubmed/20302959

This is a study done on mismatched donor transplants using ATG for T Cell depletion. I used ATG in my Allo.

“In vivo T-cell depletion with r-ATG abrogates severe acute and chronic GVHD, and allows use of mismatched unrelated donors for allo-SCT in adult pts with otherwise incurable hematologic malignancies. Long-term survivors are generally free of severe chronic GVHD, with good quality of life. There does not appear to be an increased incidence of disease relapse, and non-relapse mortality is low. This approach is safe, effective, and considerably expands the donor pool for adult pts who require allo-SCT.”
https://ash.confex.com/ash/2011/webprogram/Paper38494.html

The Allo may not be necessary with your presentation of Myeloma. It is a very big decision to make and shouldbe done in conjuction with a Myeloma specialist.. Good luck and I hope some of these links were helpful.

Mark

[Mark]

Re: When do you do SCT?

by Mark on Sat May 26, 2012 3:59 pm

SuzieQ,

Studies have shown a female donor to a male recipient has the lowest chance for relapse in Myeloma and other blood cancers.
"The reduced REL contributed to this improvement in F M indicting a gender-specific graft vs myeloma effect. Therefore, a female donor is as good as a male one for male patients, while for female patients gender disparity is a negative factor for outcome."
http://www.nature.com/bmt/journal/v35/n6/full/1704861a.html

'Male recipients of female hematopoietic cell grafts (F->M HCT), when compared with other donor/recipient gender combinations, face an increased risk for both acute and chronic graft-versus-host disease (GVHD), but also have a significantly decreased risk of posttransplant relapse. F->M HCT is characterized at the cellular level by female donor T cell responses against male-specific minor histocompatibility (H-Y) antigens, which can contribute to both GVHD and graft-versus-leukemia (GVL) activity."
https://ash.confex.com/ash/2011/webprogram/Paper44126.html

As I mentioned in my above post, use of ATG or some other form of T Cell depletion usually lower the risk of GVHD. GVHD is Graft vs Host Disease. It is when the Donor immune system recognizes the Host's tissue as foreign and attack them. That is the big risk of Allo transplant but it is also what can make them a cure. As you know, all Myeloma therapies cause side effects. Mild GVHD is the only one that can give long term disease freedom. I mention 2 studies above showing good long term QOL for patients that do Allo transplants. I do not think patients doing never ending cycles of Revlimid, Carfilzomib, Velcade, DEX, etc would likely have better health related quality of life than population norms.

You could also ask the Doctors if they like a strategy similar to this one. This use a high level of T Cell depletion and follows up with infusions of Donor Cells to provide the immunotherapy. I think this is a superior concept to Tandem Auto-Allo. This study was done on relapsed patients but could be done on a patient in first remission. Note only 1 out of 13 patients has a problem with GVHD. I will also put up a link to a youtube video of a younger patient that was involved in this study.
https://ash.confex.com/ash/2011/webprogram/Paper42075.html
http://www.youtube.com/watch?v=J2p2V8aIew8&list=UUlsUDXe46rpC-piBoYTxM2A&index=2&feature=plcp

Mark

[zephyrus]

Re: When do you do SCT?

by zephyrus on Sun May 27, 2012 7:15 pm

Kevin J wrote:
> I recognize you were asking for those who had a SCT. However, I've taken
> the other approach for now. I've been on induction treatment with CRD
> since Mar 2011, and will continue thru Jan 2013. I had stem cells
> collected in Aug 2011 so I have them in case I have a SCT later. I'm
> currently in complete response and plan to wait until I relapse before
> considering a SCT. If I can get several years in before that happens, I'd
> much rather wait. Something to consider and discuss with your doctor,
> particularly since some people have good responses with RVD.

Does "complete response" mean no lambda or kappa light chains detected in blood or urine?

[SuzieQ]

Re: When do you do SCT?

by SuzieQ on Tue May 29, 2012 6:37 pm

Mark wrote:
> SuzieQ,
>
> Studies have shown a female donor to a male recipient has the lowest chance for
> relapse in Myeloma and other blood cancers.
>
> As I mentioned in my above post, use of ATG or some other form of T Cell depletion
> usually lower the risk of GVHD. GVHD is Graft vs Host Disease. It is when the
> Donor immune system recognizes the Host's tissue as foreign and attack them. That is
> the big risk of Allo transplant but it is also what can make them a cure. As you
> know, all Myeloma therapies cause side effects. Mild GVHD is the only one that can
> give long term disease freedom. I mention 2 studies above showing good long term QOL
> for patients that do Allo transplants. I do not think patients doing never ending
> cycles of Revlimid, carfilzomib, Velcade, DEX, etc would likely have better health
> related quality of life than population norms.
>
> You could also ask the Doctors if they like a strategy similar to this one. This use
> a high level of T Cell depletion and follows up with infusions of Donor Cells to
> provide the immunotherapy. I think this is a superior concept to Tandem Auto-Allo.
> This study was done on relapsed patients but could be done on a patient in first
> remission. Note only 1 out of 13 patients has a problem with GVHD. I will also put
> up a link to a youtube video of a younger patient that was involved in this study.
> https://ash.confex.com/ash/2011/webprogram/Paper42075.html
>
> http://www.youtube.com/watch?v=J2p2V8aIew8&list=UUlsUDXe46rpC-piBoYTxM2A&index=2&feature=plcp
>
> Mark

THANKS, Mark. I will look at your links. I need to learn more. I'll post again with other questions.

[Kevin J]

Re: When do you do SCT?

by Kevin J on Tue May 29, 2012 10:54 pm

zephyrus,
Complete response (CR) is defined as:
1. No M-Proteins in blood serum or urine
2. No soft tissue plasmacytomas
3. Less than 5% plasma cells in bone marrow
I'm actually in stringent complete response (sCR) which also requires:
1. Normal Free Light Chain (FLC) ratio
2. No plasma cells in bone marrow
This is all part of the "International Uniform Response Criteria for Multiple Myeloma". If you do a search for it, you should get a link for it at the myeloma.org site.

[suzierose]

Re: When do you do SCT?

by suzierose on Wed May 30, 2012 11:16 am

Hi Mark!

I was curious as to whether the T-cell depleted Allo also requires HDT prior to the transplant?

I understand biologically why depleting the T-cells significantly diminishes GVHD..is there data that shows what the mortality rate is for T-cell depleted Allos vs non T cell depleted allos?

This concept does appear to be superior in terms of negative sequalae following an allo, I am wondering though what does it mean long-term in terms of the patients immune system? I suspect they go on to adopt the Tcells from the donor far more easily?

Which raises another question, since an allo means you are adopting the donor's immune system, do you still have to have all the immunizations repeated 1 year post Allo?

[Mark]

Re: When do you do SCT?

by Mark on Thu May 31, 2012 12:57 am

Suzierose,

I am actually getting all the vaccinations I had as a child in the next few months. I know that we acquire the allergies to drugs, etc. that our Donor had. My Donor had a different blood type than I had and I have changed over to her blood type. I would rather be safe than sorry with respect to the vaccinations - what is a few more pokes for me?

Generally speaking with Allo transplants as you lower either the conditioning or the immunotherapy the relapse rate rises. I have seen as low as 80 MEL with Fludarabine with partially T Cell depleted approaches. Typically studies that show ATG patients on par with non-ATG patients as far as not relapsing are studies where myeloablative conditioning is used. Here is a paper by Dr. Sergio Giralt arguing against ATG with reduced intensity conditioning.
http://bloodjournal.hematologylibrary.org/content/117/25/6744.full

If an Allo is done early the non relapse mortality is low IMO. From the study I mentioned above, the overall non relapse mortality is 18%, but,
"In a subgroup of patients with chemosensitivity and no relapse to prior high-dose chemotherapy who underwent transplantation with PBSCs (n = 46), the cumulative risk of nonrelapse mortality at 1 year was only 6% (95% CI, 1%–22%) for related (n = 34) and 8% (95% CI, 1%–54%) for unrelated (n = 12) donors.'

This is how ATG was used:
"All patients with an unrelated donor and 23 patients with a related donor received pretransplantation antithymocyte globulin (ATG; rabbit Fresenius, 30–60 mg/kg body weight, n = 56; rabbit SangStat, 6.0 mg/kg body weight, n = 1; and horse, 15 mg/kg body weight, n = 1)."

These are the Chronic GVHD results:
"It is interesting to note that the incidence of chronic GVHD was lower among patients who received transplants from unrelated as compared with related donors (29% versus 56%; P = .006); this was probably due to the incorporation of ATG in all unrelated transplants. Although ATG had no effect on acute GVHD, the incidence of chronic GVHD was significantly influenced by the use of ATG (23% versus 83%; P = .006). In a multivariate analysis, patient treated with ATG had a less than 2 times lower incidence of chronic GVHD compared with those who did not receive ATG (HR, 0.34; 95% confidence interval [CI], 0.16–0.71; P = .004).'
http://www.bbmt.org/article/S1083-8791(04)00272-1/fulltext

Also remember, the non relapse mortality of any Myeloma patient is not zero. It seems as if my new immune system is getting up to speed. I started feeling sick two Fridays ago at work, I was sick on Saturday, started feeling better on Sunday, and was back to work on Monday, just like a normal person. No lingering colds due to low nuetrophils from Revlimid, down immune system due to DEX, etc. The study I mentioned above said health related QOL is as good or better than the general population after 5 years. Their immune systems must be working just fine and certainly better than a patient on never ending cycles of Myeloma therapy.

Mark