Rest In Peace, Tayah Fairbrother

Tayah Fairbrother was part of our neuroblastoma family.  We did not know her very well, although we have seen her many times at the clinic.  By all counts, Tayah was an amazing child. In a short period of time, as can be the case in our NB circle, we’ve got to know Mark and Candice Fairbrother.   Mark and Candice are amazing parents.  They are the type of parents, we all wished we had when we were growing up.

Tayah and Mark

Tayah chose her parents well in choosing Mark and Candice. The degree to which Mark and Candice went to help Tayah was astounding.  The level to which Mark and Candice went to advocate for Tayah was awe inspiring.  We really wanted for Tayah to pull through.  What I am sure is that the amount of suffering that Tayah may had to experience was minimized by Mark and Candice’s advocacy.

It’s heart breaking to see another child taken by the disease.  And our hearts are breaking for Mark and Candice.  Rest in Peace Tayah.  May your parents find peace in knowing that they did everything in their power to help you through this world.

St Jude Summary

St. Judes is a world class research Hospital.  Dr. Tal Schechter-FinkelStein, our BMT doctor in Toronto went out of her way to get Maya down to St. Judes.  And gosh, she really went out of her way!  We’ve just returned from our initial consultation.  We’ve had a battery of tests and had the opportunity to meet with everyone who will be involved in our care.  Three of the doctors we’ve met are Dr. Brandon Triplett (Chief Investigator), Dr. Momcarz (fellow) and Dr. Pai (Radonc).

Dr Triplett

There are three main factors that have overall outcome; Disease Burden, GVHD and Relapse.

Disease Burden:

Smaller the burden going into BMT, better the outcome.  It’s simple as that.  Matter of fact, some patients are in complete remission and they still undergo the therapy.

GVHD

Graft Vs Host Disease is a man made disease and come about as a result of the allogenic Translplant.  Namely, putting in the donor’s blood into a patient causes the recipients body to violently object to the process.  The donor’s blood and the recipients blood go to war with each other.  If an acute GVHD develops, it is fatal.  Until a few years ago, GVHD took up approx. 1/2 of the “Non Relapse Mortality”.  The other common complications are due to infections.

GVHD is all about naive NK-Cells and the fine balance thereof.   To a large extent,  we need the selective NK-Cell functions.

  • donor NK-cells should not attach the recipients tissues.  (GVHD)
  • donor NK-cells should attack recipients blood products.  (GVTE, Graft Vs. Tumor Effect)  This is the part that you do want.  We want the donor T-cells to destroy the recipients blood component including the cancerous cells.

Relapse

With blood cancer, relapse is a big deal.  You need to get rid of all the cancerous cells.  Simply relying on the chemo does not work well.  Hence, autologous transplant is not an ideal therapy.  You really need the graft vs. tumor effect.  The donor blood cells, once grafted, will seek out and destroy the cancerous cells in Maya’s body.

And this is where the balancing act comes in.

  • NK Cells cause GVHD.  But, it’s the naive NK cells that are the culprit.  Naive NK cells are those cells that have not been activated.  That is, “called” to battle.
  • So, NK cells are severly reduced from the transplant.  Approximately 1/1000 th will make it to the host.
  • In order to reduce GVHD, Total Limph Node irradiation (TLI) is performed as well.  We don’t want the “nuclear bomb” to go off inside maya.  Even with such reduction, GVHD can still occur.  However, GVHD at St. Judes is in the 5% range, as opposed to 20 – 65% reported prior to these two adjustments.
  • Since you reduce the NK population as well as have a limited number of T and B cells, you are open to infections.  You are likely to get viral, bacterial and fungal infections.    And until the stem cells graft, which typically takes 10 – 20 days or so, you are severely immune compromised.
  • The “study” part of the treatment is that within these parameters, the doctors will add NK cells at some point to see if that has any positive affect.

Yes, the therapy is tough.  And yes, there is mortality associated with the therapy.   The big concern with Maya is that she’s been heavily treated.  So, in this sense, it’s not certain how Maya will respond to the therapy.  That’s part of the reason why St. Judes takes Maya’s overall condition under consideration.  Dr. Triplett has turned down patients, because he did not feel that the therapy may benefit the patient.  In other words, as difficult as it may be, he has turned down patients because he felt that the patient was strong enough to survive the therapy.  Thanksfully, Maya is not in that category.

St. Judes also has a set of guidelines.  For example, if the rate of Acute GVHD is greater than 10 %, St. Judes will shutdown the study.  Also, if Non Relapse Mortality rate is greater than 15%, St Judes will also shut the study down.  In other words, St. Judes Guideline is that if they are losing roughly 1/4 of the subjects, the study will be shutdown.  The fact that the study is open and recruiting candidates, implies that the mortality rate is lower than 25%.  So far, in this particular study, they’ve done well.  There were 8 patients so far, and although not discussed in detail, it seemed that all of the patients have survived thus far.

Although this study is relatively new, the “back-bone” therapy has not changed in 10+ years. That is, the use of KIR mismatched, haplo transplant.  Each new study has been a progressive refinement of the initial idea.  So, while one can’t rely on the statistical measures here, the overall difference would not be significantly different.

Dr. Pai

Dr. Pai is a Radiation oncologist.  In this study, part of the protocol is a Total Lymphoid Irradiation (TLI).  It used to be that the protocol used to involve total body irradiation (TBI).  However, TBI did not increase the overall survival (OS).  Hence, TLI came about.  The objective of the TLI is not to kill the cancer cells, but rather, to immune suppress the patient further.  The suppression in turn will help with the grafting and subsequently with relapse. The overall numbers were impressive.

In terms of dealing with GVHD in the 50 – 65% range, now, Acute GVHD occurs in less than 5% of the patient. And overall side effect were all temporal and not burdensome, because the overall amount of radiation is significantly less.

With our consultations,  I felt much better about heading into this therapy.  Would I choose to walk through these gates, no.  Will it be fraught with difficulties and challenges, absolutely.  Is there a significant chance that Maya succumb to therapy?  Yes.   But… it really is the best option for us now.

  • Will Maya develop GVHD?  How will I deal with this potential outcome?
  • Will Maya graft? If so, how long?
  • How much discomfort will Maya have to endure?
  • How much additional damage will we done to Maya?
  • Will we all come home?

These are not easy questions to entertain.  But, it is with hope we proceed.

Often, I will take a giant step back, insofar as I am capable of it, and take a look at ourselves as well as those around us.  Yes the medical science is severly wanting.  We are lead down a path that is so difficult to walk.  Sadly, that will not change anytime soon.

What I do see is the “true color” of human nature. I see it from our neighbor who so kindly shovels our walkway or makes us dinner on the night that we returned from St. Judes.  I see it from the teachers at Maya’s school.  I see it from other (NB) parents, who always keeps an eye out for us.   I see it from our colleagues at work.

But mostly, I see it in my little daughter’s eyes.  She is the epitome of “Joi de vivre”.  She celebrates life each and every moment of her day.  Whether she lives another year, or another 80 years, I don’t think it matters as much as how she lives it.   Her joy comes from her inner self.  It really has so very little to do with us, the parents. If there is small credit that we might take as her parents, it is that we did not cover or smother her light.

Hey Jude, We Luv Ya!

It’s been a hard few days.  We were on the go non stop ever since we got here.   Coming to St Jude has been very fruitful. There is so much to write about.  Hopefully, I’ll catch the major theme here.   Like Helen Vos Centre in Grand Rapids, NIH in Washington, and here in Memphis, health care is world class.  It’s beyond outstanding really.  While I can’t be sure, I suspect that the ratio between “the machine”, and the patients is 4-5 : 1.  That is to say, there are 4 – 5 health care provider per patient.  Of course, I am not sure and it would not surprise me to find that the ratio is higher.  It’s jaw dropping.  And completely not sustainable.

Once we’ve arrived, our itenerary has been filled to the brim.  Let me see… Here’s today’s itenerary:

  • 7:00 – 8:30  Echo / EKG
  • 8:30 – 9:00 Child life services (Education)
  • 9:00 – 9:30 Surgery Pre-op
  • 9:30 – 11:30 Bone Marrow aspiration and  Biopsy
  • 11:30 – 12:30 ICU recovery
  • 1:00 – 2:30 PM  Radiation Oncology Consult.
  • 2:30 – 3:30 PM Eye clinic initial consult
  • 3:30 – 4:30 PM.  Preliminary discussion of the Bone marrow Aspiration

I think one of the surprising thing was that the schedule for the most part, flexible.  Bone Marrow Transplant Coordinator moved the schedule around.  “We’ll drop this appointment for next week, and we can move that appointment up…”  This kind of rejigging was a daily occurence.  It was done in a matter of fact manner.  WHAT?????  You mean, if we miss this appointment, it’s not a big deal?  “Oh no… we’re here for you!”  is what we’ve heard with  a southern  draw.

With the most important consults over with, we’ve made a decision not to start right away.  Right away meant that next week would be additional scans and preparation, starting the therapy on Dec 23rd.  We wanted the Christmas and Maya’s birthday at home.   Right after Maya’s birthday, we would be travelling back to Memphis for 3 – 4 months.   Now the implications:

  • Maya is undergoing a battery of tests to assess if she can handle the therapy.  So far, so good.
  • I am still the primary donor.  So far, so good.
  • Dr Triplett, the principle investigator, thinks that the particular type of MDS that Maya has is unfavorable.  We’ve been told this before at sick kids.   But the context made the gravity of the situation very real. We know that Maya’s disease moved very quickly when we were first diagnosed.  Roughly within 2 months, Maya’s MDS went from no blasts to > 25% blasts.  It moved very very quickly. Luckily, Vidaza did wonders for us.   So, it’s not unreasonable to think that once the disease starts to progress, it can become very serious within two months.
  • If the disease begins to progress in full force, we could be in deep trouble within two months. The difference is, we would not have a drug to fall back to.
  • Now, if we come back to St Judes in Jan 5th ish, we still have two weeks of preparatory work.  That puts us at 5+ weeks before we can start the bone marrow transplant.

Presently, we have a very small disease foot print.  However, if the disease has started to progress, in 5 weeks, there may be significant amount of disease such that the transplant may not work.  But, Maya is looking so forward to Christmas and her Birthday.  How do we tell her that we won’t be home for Christmas and her Birthday?  And under this scenario, if things don’t work out, how will Indira and I feel about not giving Maya her last Christmas?

Yup… It’s a double edged sword and a rock and a harder place!  We are coming home.  We’re scared.  We can only cross our fingers and hope.  We need to dodge this one last bullet.  If Maya relapses, then that will be that. Both Indira and I are spent.  We have been scanning and testing and consulting under extreme duress.  Maintaining the fascade of civility under our current predicament is a participation in the theatre of the absurd. Our bodies ache from all the adrenalin rushing about in our bodies.

But here we are…  We are coming home.  We will celebrate life as we have never before. Then, we will return to face the piper.

Thank You, Thank You Very Much…

I’ve been here well enough before.  It’s 2:30AM and sleep can wait a few more minutes.  Bjork and I are on a rampage.   Well, I am fighting off the morning.  Bjork, she’s just watching “the human behavior”.  In a handful of hours, Indira, Maya and I will be on our way to Memphis.   In the past few days, I’ve been searching through the cyberspace, trying to understand what we are heading into.  Podcasts, journals and Khan Academy and even Wikipedia.   It’s easier to learn now than ever.   I like immunology.  It’s not too different in someways, from Computer Science.  For example, “garbage collection” and immune response are similar.  Gene is to Class as Protein is to Objects.  Or cytokines are like messaging in Comp-Sci.   Ok… Whatever.

There are a slew of emotions that we’ve been dealing with. Certainly, fear and sadness are the dominant emotions.    Also, the greatest disconnect is the gravity of the situation we find ourselves in and how Maya comes across.  Maya is great.  Never have you seen a happier and well adjusted (or shall I say misadjusted?) 8 year old.  Yes, Maya will be 8 years old soon.   She is eating well, there is so little sign of any illness when you look at her.  And she loves to go to school and play etc.  She also loves to read!  She’ll devour 20 – 30 age appropriate books when we are in clinic.  She is a perfect little girl.

You pull out her medical records, it’s a completely different story.  Stage 4 neuroblastoma, unfavorable histology, NMYC non-amplified (Thank god for that!).  Therapy induced MDS. Unfavorable also with (1,7) and (11,17) translocations.  Again, clinicians talk about “challenges” and “difficult” to treat.  Even though Maya looks so well, we are heading down an uncertain path; one full of pitfalls and traps.  Again, we do this blindfolded.

Here is an example of how we ended up in Memphis.  About 15 months ago, we found out that Maya developed MDS.  At that point, The Army of Sick Kids came together to discuss the next steps for Maya.  Attendees included, Oncologist, Haematologists, Bone Marrow Transplant Doctor, Social Worker, Nurse Practitioners,etc.  St Judes came up in the discussion, but there were no spots available in the study.  Hence, a decision to try Vidaza came about.  At that point, the thought was that Vidaza may stop the progression for some period of time, but the disease will inevitably come back.  We likely did not have 9 – 12 months before the disease took over.      The only curative therapy available is a Bone Marrow Transplant.  May be, as relapse rate is still unacceptably high.    Of course, BMT almost killed Maya.

So then, the name of this game last year was maximizing our time with Maya with good quality of life.  That meant keeping Maya on Vidaza as long as possible and only going for BMT when it is absolutely necessary.  Why?

  • BMT is a brutal therapy.  Patients die from the therapy either through complications such as infection, or through relapse.  Imagine a canker sore and how much it hurts.  Typically, these canker sores are about the size of a grain of rice.  Now imagine having a canker sore all through your mouth, throat, and through out the entire GI track.  This is but one side effect of the therapy.
  • We’ve had almost four years of therapy.  We have been poisoning Maya under a controlled setting.  Maya’s body has been weakening for four years.  Maya’s body may not be able to handle the rigors of the therapy.
  • Relapse rate is still very high.  In one paper I read, relapse rate is over 50%
  • By putting Maya through the therapy, we may in fact could shorten her life.  Our BMT Doctor did not feel confident that Maya will be able to handle another BMT.

So, delay BMT as long as you can and enter that door when we all but run out of options.  OK, it’s not a bad plan.  It’s not that easy.    What is the state of Maya’s blood disease?  We don’t know.  We never know… and that’s part of the problem.

  • Technically, we’ve relapsed.  We could not find any evidence of the disease for a (short) while but now, we see it.   We’ve found 2 / 70 bone marrow cells that have the genetic mutation.
  • So…how aggressive is it?  Don’t know.  In other words, how much time do we have before we need to be in BMT?
  • Could it just be there before and we didn’t see it?  Or is this a relapse?  Don’t know.
  • Could we be chronic?  Some people go years on end without any progression.
  • How fast would it start to impact Maya’s blood system?  Don’t know.
  • Should we be going for transplant now?  Haematologists would like us to.  Patients who have only a residual amount of disease tend to fair better than those who have a lot of disease still.  But, they don’t talk about the fact that majority of the patients succumb to the disease through relapse.
  • Even if we make it through BMT, if we relapse, it will mean that Maya will die.  We will have run out of all the wild cards.

We know we need another BMT.  It’s a Russian Roulete.  Is this the bullet that will take us out?  Don’t know.  Will our decision be the right one?  Don’t know. And while we can say that we made the best decision with the limited available information, we’re talking about our child’s life here.   Too many don’t know’s.  And we don’t have any additional information to guide us.  We are running out of options.

Having said this, given this additional year, our BMT doctor found us a spot on the St. Judes clinical trial.  We also had to face challenge after challenge trying to become eligible.  Our BMT doctor went well, well, well beyond her duty to get us to St. Jude.  Given the desparate situation we found ourselves in, our BMT doctor pulled a whopper out of her hat!   She could have easily said, we did not qualify. And for her to have taken such a position would have been easily justifiable both technically as well as morally.   She could have said that she’ll treat Maya at Sick kids.  But she did not do that. She got us here to St. Judes.   You have no idea how thankful and indebted we are to Dr. Tali.  So thank you Dr Tali!    Gosh, is there somewhere I can nominate Dr. Tali for an award???

We will have many days of tests to run.  In the course of next few days, we will have a better idea on what is right for us.   For now… sleep… go away…  Tomorrow can wait just a few more minutes.