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Hi Shaz, yes I did have a 'mini' sct and yes I was treated with 400mg imatinib daily for 11  months post sct. This is to keep the residual disease left after the sct (owing to less chemo being used) under control until you can get a safe enough distance from the transplant to guard against serious GVHD. DLI (donor lymphocyte infusion) is used to clear the residual leukaemic cells and so this is the 'cure' part for most people.... although, on the study I was on, there were a few people who did not need DLI and were 'cured' with the transplant itself. I had to have 4 DLI's before the residual disease disappeared, this took over 18 months after I stopped taking the imatinib. I had the sct in 2003 but it was not until early 2006 that my pcr's were clear of bcr/abl.... they have been clear since then.

In fact it is 7 years now since my transplant on October 20th 2003. Another anniversary, another celebration of how fortunate I have been.

Best wishes,

Sandy

Hi Shaz

I am 3 years post stem cell transplant today!

I have been PCRU since the transplant and have not taken glivec post transplant. I was intolerant to both glivec and dasatanib which is why I had a transplant. I had the 'mini' transplant with reduced chemo and no radiation. Above a 'certain' age this is the preferred way. 

regards

Susan

Dear Alyson, good to hear you are doing well.

I was part of an ongoing study at Hammersmith (in partnership with Birmingham Queen Elizabeth) which is now at several other UK centres, that used TKI's after mini-allograft and before DLI.

The reason to use TKI's in this way is to control any residual stem cells and keep them at as low a level as possible for as long  as possible - at least 12 months- before DLI is used to wipe out the remaining disease.

The majority of patients who have a 'mini-allograft' are expected to have some of their own stem cells left after the conditioning treatment with chemotherapy. The level of residual disease cannot be quantified at this point as blood tests show all cells have dropped to zero and the 'old' cells appear to be gone- and if we are talking about all the mature cells then this is probably true- but in most cases there are probably one (or maybe more) of your 'old' stem cells left hiding somewhere in the marrow.

Maybe these are the 'quiescent' stem cells that are not in active mode, that we hear so much about about. There are a lot of research teams that are trying to identify the mechanism behind the 'quiescent' stem cell that ensures (its) survival in spite of chemotherapy/TKI etc. 

When the donor cells are finally transfused (in my case after 5 days of chemotherapy drugs, followed by 2 days 'rest') there is a short period (some weeks) before evidence that the donor stem cells have engrafted in the marrow and are starting to produce the blood cells that will form the new (donor derived) immune system.  

Graft versus Host Disease (GVHD) is as much a problem with mini allografting as it is with traditional transplants. The new blood cells which are produced, in the marrow, by the donor stem cells, need time to get used to you (the new host) and agree to recognise you as part of them- in other words, they are in charge and if they identify your other cells- skin/gut cells etc- as foreign to them then they will deal with them accordingly. This is why GVHD can be a serious problem and at acute or chronic grade 3 and 4 it is life-threatening.

However, the rationale behind the study I was part of, and still am, is this.

It is known that the longer the gap between donor stem cell engraftment and the infusions of donor mature lymphocytes (DLI) the less likely it is that these mature donor lymphocytes will see you as their enemy. My doctor explained that it is considered that a gap of 12 months (at least) is more or less a safe distance. You and your new immune cells will have got more used to each other and when the donor lymphocytes are infused (remember these are mature lymphocytes and were separated from the stem cells taken at donation) they are pretty strong medicine! This is classified as immunotherapy.

These donor cells will seek out and attack cells that they do not recognise - any original cells from your own immune system- and this is why, when the right level of infusion is reached,  all the residual disease will disappear and you are considered 'cured'. 

The level of donor lymphs given at each infusion is also crucial. I started off with a very low infusion of 2.5 million which my doctor told me would have little or no effect on the residual disease. However, he said that they had learned to proceed very cautiously and only increase the levels over several infusions. This meant that in my case 4 infusions were needed all together- each one with more cells than the last. The 4th one infused 50 million donor lymphocytes and 12 weeks later that proved to be the magic number for me. 

This is why it took so much patience (and nerve) because there is a 12 week gap between each DLI to see if it has worked. Some patients on the study responded to lower levels of DLI and only needed 2 or 3 infusions.

Another thing worth saying is that even though I had relapsed because of an imatinib resistant mutation (Y253H) I was still enroled on the study (there was little option as dasatinib was not available just at that time). My doctors at Hammersmith thought it worth trying in spite of resistance to imatinib... and they were proven right, and to their own surprise as well as mine, I regained sensitivity to imatinib after the SCT, and it kept bcr/abl at very low levels for the initial 11 months post transplant and even had a residual effect.... my pcr's did not start to rise significantly for a further 6 or so months after I stopped TKI treatment.

You should discuss the possibilities with your doctor... I understand that Hammersmith (and certainly Prof. Charles Craddock at Queen E Birmingham) wanted to start another study using mini-allograft + nilotinib + DLI.  However I am not sure of the details and I think there was talk of using the TKI part for an even longer period, just to make sure that GVHD would not be a negative factor in any patients case.

It might be good if you asked your doctor to talk with either Prof. Craddock or Dr. Marin (Hammersmith)- about the newer studies.....let me know if I can help further with contact details.

I hope this rather long winded explanation has helped answer your questions. 

Best wishes,

Sandy

That's brilliant Sandy - I am SO delighted for you!

Love beth