Wednesday 7 November 2012

Will the Allogeneic Stem Cell Transplant cure me?

Those of you that read my previous post will know that I recently went for my initial visit to the hospital in Leeds, i.e. the hospital where I will potentially have an Allogeneic (from a donor) Stem Cell Transplant in the near future.  The purpose of the initial visit is really just an information gathering exercise for both parties, as it pretty much just involves a discussion between the doctor and yourself about a few things relevant to the treatment (there was yet more blood tests too):

  1. The first topic was that of my medical history, which was mostly about anything other than cancer, as details about my Hodgkin's Lymphoma treatment had already been provided by the hospital where that took place; However, any potentially relevant health issues within my family was also discussed, and it was there that any history of cancer was of more interest.

    Note: Hodgkin's Lymphoma is not hereditary, so I assume the interest in the history of cancer within the family is more about what types of cancer I may have a higher risk of developing in the future; Ironically, one of the potential side effects of cancer treatment is cancer.

  2. The second topic involved the doctor clarifying/explaining how an Allogeneic (from a donor) Stem Cell Transplant works, and how that differs from the Autologous (from yourself) Stem Cell Transplant that I had undergone previously.  In a nutshell, they work as follows:

    • Autologous Stem Cell Transplant

      It is essentially a three step process: the first involves harvesting some of the stem cells from the patient, the second involves giving the patient a high dose of chemotherapy, and the third involves returning the previously harvested stem cells back to the patient.

      The treatment in this type of stem cell transplant is actually just the high dose of chemotherapy, i.e. the stem cells are only harvested and later returned because the high dose of chemotherapy pretty much wipes-out the patient's stem cells, and without them their body is unable to replenish the components that make-up their blood.  In other words, it is the harvesting and returning of the stem cells that enables such a high dose of chemotherapy to be given, in the hope that it alone will wipe-out any traces of the cancer.

    • Allogeneic Stem Cell Transplant

      It is similar to the Autologous Stem Cell Transplant, in terms of being a three step process, but: the stem cells are harvested from a donor that is suitably matched to the patient, i.e. not from the patient themself; the dose of chemotherapy may be of a reduced intensity; radiotherapy to the full body, which is often referred to as total body irradiation, may also be used (in varying doses); and finally immunosuppressive therapy is used (also in varying doses) to prevent both the patient's and donor's immune systems from launching undesirable attacks at different stages of the stem cell transplant.

      Note: Reduced intensity chemotherapy and a single session of total body irradiation is on the cards for myself, as just like with the vast majority (if not all) Hodgkin's Lymphoma patients undergoing this type of stem cell transplant I have been heavily pre-treated, and consequently a less aggressive approach is favoured as it avoids giving my body yet another severe beating - one from which it is potentially no longer able to recover, as the various treatments to date, despite being unsuccessful, still tend to take their toll.

      The treatment in this type of stem cell transplant actually comes from the stem cells of the donor, as it is those stem cells that result in the patient inheriting a new immune system, i.e. one that can hopefully wipe-out any traces of the cancer.  In other words, the chemotherapy, potentially radiotherapy, and immunosuppressive therapy may in part result in the wiping-out of some of the cancer, as a kind of side effect (and in doing so help with controlling the disease), but their main purpose is to allow the donor's stem cells to eventually replace those of the patient, and consequently for the patient to inherit a new immune system, which in turn can set about wiping-out any traces of the cancer.

    A key difference between the two types of stem cell transplants is that with the autologous variety the only concern post-transplant is whether the disease will relapse, but with the allogeneic variety, in addition to the potential for relapsing, there is also the possibility of developing a condition that is known as Graft Versus Host Disease (GVHD).

    GVHD is when the donor's immune system (the 'graft') attacks the patient (the 'host'), hence instead of it just wiping-out any traces of the cancer it is also targeting healthy cells too.  This is because immune systems have an innate ability to recognise cells that shouldn't be there, e.g. cancerous cells, so that they can wipe them out, and that inherently means they also recognise what should be there, so that they can leave them alone; However, that innate ability is for the person born with that immune system, so by indirectly transplanting that immune system into someone else that innate ability can get it wrong (to varying degrees).  The reason this happens is that the donor's immune system is only ever a close match to that of the patient, i.e. it is not a perfect match as everyone (identical twins aside) is at least slightly different - Clearly, some difference is essential too, as the donor's immune system needs to be capable of curing the disease, i.e. wiping-out what the patient's immune system was unable to do itself.

    There are two types of GVHD: acute and chronic.  Typically, acute is observed within one hundred days of the transplant, and chronic at any time after that.  GVHD also varies in severity, and that severity can be either: mild, moderate or severe/life-threatening.  The skin seems to be the most susceptible to GVHD, as those that get either type of GVHD tend to encounter problems in that area (e.g. rashes, itching, dryness, tightness, and/or redness like severe sunburn with peeling or blistering), and whilst it tends to be localised to the hands and feet initially it can become widespread.  The other main areas that are susceptible are: the liver, resulting in the yellowing of the skin and eyes; and the gastrointestinal tract, e.g. stomach and intestines, resulting in cramps, nausea, and/or watery or bloody diarrhea.  Chronic GVHD can also result in eye, lung, and/or tendon problems too.  In short, it can be pretty unpleasant.

    Some GVHD can actually be beneficial though, as after an Allogeneic Stem Cell Transplant immunosuppressive therapy must be used to keep the donor's immune system from getting carried away, i.e. targeting healthy cells due to its innate ability to recognise such cells being a little off, but how much exactly is required involves a balancing act, as suppressing the immune system not surprisingly results in an increased risk of infection, hence GVHD can provide a useful indicator for determining how much is needed to achieve that balance.  In other words, by giving just enough immunosuppressive therapy to keep the GVHD under control the donor's immune system remains active enough to hopefully wipe-out any traces of the cancer, which is known as the Graft Versus Tumor (GVT) effect, whilst at the same time minimising the increased risk of infection.  Retrospective analysis of patients that undergo this treatment also shows that the probability of the cancer relapsing is decreased in patients that get GVHD.

  3. The third topic involved the doctor stating the probabilities of: the Allogeneic Stem Cell Transplant failing/succeeding, and developing the different types and severities of GVHD.

    The Allogeneic Stem Cell Transplant tends to: be successful, i.e. provide a new immune system and cure the disease, in about fifty to sixty percent of cases; be rejected or buckle under the pressure, i.e. fail to even provide a new immune system, in about ten percent of cases; and either fail to cure the disease or further down the line result in the disease relapsing, i.e. provide a new immune system but one that ultimately doesn't cure the disease, in the remaining cases.

    Note: For the patients where the disease is not cured or later relapses, they are then treated with: the antibody treatment that I'm currently on, i.e. Brentuximab Vedotin; and/or donor lymphocyte infusions (DLIs), which can be thought of as top-ups of the donor's immune system.  As it happens, should I have the Allogeneic Stem Cell Transplant, I will be the first patient that they have had that has been given Brentuximab Vedotin prior to the transplant.

    In terms of GVHD, approximately one-in-four develop the acute type of the disease, of which about ninety percent of those encounter symptoms that are at most either mild or moderate in severity, and between thirty and forty percent develop the chronic type of the disease.  Each patient may develop both types of GVHD, a single type of GVHD, or neither type of GVHD.

    To illustrate how performing the reduced intensity transplant that is on the cards for myself compares with that of a full intensity transplant, in terms of the probability of a patient like myself (albeit based on some predicting of future test results) still being alive in two years, the doctor entered the appropriate information into his computer, and it stated the reduced intensity transplant would result in just under a seventy percent survival rate, whereas the full intensity transplant would result in a significantly lower survival rate of only forty percent.

    Note: It is only in the more recent years, when the path of reduced intensity transplants for patients such as myself was found to be favourable, that the true curing potential of Allogeneric Stem Cell Transplants could start to be seen, as previously the full intensity transplants were proving too much for many patient's bodies to cope with, and consequently it was the treatment itself that was reducing the survival rates, rather than the disease not actually being curable.

    Finally, it was mentioned that in approximately one-in-five cases, the patient does not survive the Allogeneic Stem Cell Transplant, due to some kind of complication; Therefore, when compared to an Autologous Stem Cell Transplant, where about about one-in-twenty do not survive, it does still have a significantly higher rate of treatment related mortality.

  4. The fourth topic involved a discussion about what happens next, which ultimately boiled-down to what the doctor was hoping to refer to as the four Ds: disease, donor, fitness and desire.  Even the slowest amongst you will have noticed that one of those is lacking a 'D', so until someone can think of a 'D' for fitness, then it's actually three Ds and an F.  To date, the best alternative to 'fitness' I've thought of is 'condition', which at least actually has a 'D' in it!

    The number of Ds aside, the mnemonic is intended to help with remembering what is required for the Allogeneic Stem Cell Transplant to be a possibility: "Disease" represents the need for having the cancer under control; "Donor" highlights the requirement for having someone that can donate suitable stem cells; "Fitness" emphasises the patient must be well enough to cope with the treatment; and "Desire" illustrates even if all of the other criteria are to the doctor's satisfaction, the final decision about whether to proceed ultimately rests with the patient.

    Whether my cancer is under control is currently unknown, but the PET scan arranged for a couple of weeks from now should either show that I'm currently heading in the right direction, i.e. further antibody treatment is required, or that the antibody treatment has already failed or succeeded.  The doctor seemed to suspect that if I'm going to get my cancer under control, I will probably require six treatments, and at the point of the PET scan I will have only had four, hence the prediction is that the Allogeneic Stem Cell Transplant would be more likely to take place in January than December, particularly given that December is currently fully booked.

    An unrelated stem cell donor has been found on the register, in the form of man that is under thirty; Such a donor has an increased probability of achieving a positive outcome.  I assume that exactly how good of a match this donor is for myself is not fully understood yet, as whilst at the hospital in Leeds I had numerous blood samples taken, and I was given the impression that at least some of those were intended for performing detailed matching, hence at this stage it would seem that only the preliminary matching has been performed.  That reminds me, when the nurse went to get the empty blood sample tubes and came back with both hands full of them, I did wonder if the plan was to bleed me dry, but despite filling all of them (and half filling a faulty one) I still managed to walk to the car and drive home without fainting!

    In terms of fitness, other than being a bit more tired than normal, I feel fine.  However, there is more to it than that, as heart and lung function tests need to be performed.  I have had these done previously, but they were a few months ago now, hence they need repeating.  Also, my last lung function test showed that I was only operating at about sixty-five percent of what would typically be expected, which is definitely on the low side, and would mean that the two year survival rate that I mentioned for myself previously is somewhat optimistic, as in reality it would actually be about half that.  However, only a ten percent increase would bring the two year survival rate back to what was predicted, and it is perfectly possible that my lung function test will show such results this time, as when I had the previous one I was suffering from an infection that was amongst other things causing me to much more easily become out-of-breath.

    That just leaves the question of whether I actually think the Allogeneic Stem Cell Transplant is the best option for me, assuming of course that I meet all of the necessary criteria for having it in the first place.  As you can probably imagine, everything that I've described above certainly gives me plenty to think about, but at the end of the day this treatment is the only one that potentially offers a cure, i.e. the alternative is just palliative care, so whilst there is no guarantee that I will be cured by (or even survive) the treatment, and I could potentially end-up with side effects that affect my quality of life, palliative care still doesn't sound like much of an option.  Either way, the question could be academic, as I need to wait for the various test results first.

1 comment:

  1. Be Aggressive! Attack this disease and win!