This past Wednesday evening was somewhat troubled night for me.   Maya’s platelet clocked in at 7 last week and it’s been a week since Maya had a platelet transfusion.  I was worried because Maya had caught a cold and was sneezing a lot.  Sometimes she would sneeze holding her breath.  I was picturing internal hemorrhaging due to the excessive pressure build up.   Of course, we all hold our breath when sneeze sometimes.  And the pressure will pop little blood vessels as a result.  But platelets will patch up the damage incurred.  In our case, well ?  It’s an issue, isn’t it? I wasn’t sure if such a trivial matter could turn more serious.

On Thursday when we went to the Haemotology clinic, I was very studious of the checkup process.  In addition, I also asked a bunch of questions to our wonderful Nurse Practitioner, Mary (NP).  In terms of the check up, we were doing most of what Mary was doing:

• Check for bruising.  (No platelets, no clotting, bruises)
• Check for Petechia, which are little red spots on the patient’s body.  These are little ruptured blood vessels. Maya tends to get them around her neck and around her eyes, when platelets are low. She will also get cracked lips.  These little indicators tell us that platelets are getting low.
• Check lymph nodes.  Just watching out for infections.
• Check her abdomin for any tenderness.  Also, for infections.
• Check for edema.  Just push on her fingertips or toes to see if there is excessive fluid in her system.
• Of course, we have to watch her vitals (Heart rate, temperature and blood pressure)

If there are anything serious going on, generally speaking, Maya will not be feeling well and we need to get her to the emergency or get her in to the clinic. With the minor questions out of the way, I had an opportunity to consult with Dr. Cada about our decision.  The consultation went very well, I thought.  Briefly stated, we want to start on Vidaza now and at some point, head into BMT.  In terms of therapy, Bone Marrow Transplant is the only viable option.  The timing on BMT depends on a few factors:

• What’s the status of Maya’s neuroblastoma?  The state of her NB will also impact the conditioning regiment used in BMT.  If NB is active again, the conditioning regiment will need to work on both NB as well as MDS/AML.  We are scheduled for a MIBG scan next week.
• What’s the status of Maya’s MDS/AML?
• Is Vidaza efficacious or not?
• How’s Maya’s health?

At the high level, it seems relatively simple.  Once you step into the trenches, it’s a bit more tricky.  For example, how do  you know if Vidaza is working?  You can’t rely on the peripheral blood results.  That means one must get access to the bone marrow and that is not so easy to access.  If there is a remarkable decrease in the blast count in the marrow, awesome.  If consistent count?  Ummm ?  If it increased ?  Well, I guess much would depend on by how much.  If little, then, we would need to look for a trend line. If significant, then we’re looking at BMT in a hurry.

So, in the consultation, the decision was this.  Let’s start on Vidaza.  We will to a Bone Marrow Aspiration subsequent to the first round.  We’ll see if there is improvement.  If so, continue on.  If not, then we’ll need to reassess.  Subsequent BMA could be considered a month or two later.

What I like about this approach is that the decisions are made based on the “as needed” basis.  Maya is special, and she marches to her own genetic drum, so to speak.  So, what little info we have on pediatric MDS/AML is taken with the caveat, which is Maya’s physiology.

In the mean time, we will get the cytogenetic results back, as well as the MIBC scan results.  These results will add to our subsequent decision making.

For a little while, we can take a breath and adjust to this new world.  In the past, I have lamented over the fact that Maya is different.  I did not worry about the statistical median, but rather the outliers.  This has always been Maya.  And now, we have to believe that Maya is also an outlier to survive the storm that’s brewing.  It will come.  Soon, we’ll have to nail things down again.  Bar up the doors and nail down the windows.  And if you don’t look too closely, you can only see puffy little clouds on a sunday afternoon.

[KHK]  Vancouver photos

Maya and I’ve decided to come back to Vancouver.  Since we got back last week, I felt somewhat cheated for not taking advantage of the two weeks that was left in August.  We spent a week just catching up being at home.  It was lovely!   But rather than staying home for the second week, over the past weekend, I’ve decided to come back out to Vancouver.  We have a week left!  And since I did not want to idly spend the time at home, on a whim, I decided to bring Maya back out to Vancouver.  My sister Susan lives here and when we were here just under two weeks ago, Maya had a great time hanging out with my sister Susans’ two little dogs, Dagee and Chokomon which respectively means pig and tiny in Korean.

Two weeks ago, we started our journey back to Grand Rapids, Michigan.  We left around noon on Monday Aug 13th and we arrived in GRR Wednesday night around 2 AM. So, a solid 3 days of hard drive got us back home. Because Dr. Gisselle Sholler (Maya’s U.S Oncologist,a real hero, IMHO) wanted to see Maya, we didn’t get to see a couple of places that I wanted to see with Maya; Vancouver and Yellow Stone. Well… Haida Gwaii and Alaska will have to wait.  But I am motivated to get there not too distant in the future.

The fact that Dr. Sholler called us back did not sit with me very well. In light of the fact that Maya’s platelets were misbehaving, the drive back to GRR was a somber one for me.  I had nothing to do but drive and brood for three days.  And these types of ill feelings are not something that one can share.

The synopsis of Maya’s hemotology is as follows:

• July 13:  Bone Marrow Biopsy and aspiration is clear. We noticed a slight decrease in platelets.
• July 18: Maya’s CBC shows 6% blast cells (Immature white blood cells) Not abnormal, but nevertheless, noted. Her platelets came in at 46.
• Aug 03: San Diego. Another CBC, Maya’s platelets came in at 26. Platelets were transfused.  Blast cells up to 12%
• Aug 10: San Francisco. Maya’s platelets came in at 55.  Still pretty good. Blast cells up to 20%
• Aug 16: Grand Rapids.  Maya’s platelets were down to 11. Blasts up to 25%.  Platelets transfused.
• Aug 20: Another bone marrow aspiration back at Sick Kids.

Blasts are immature white cells. It is not abnormal to see some blast cells in the blood under some circustances, such as fighting off an infection.  But, what we found out is that Maya has developed something called Myelodisplasia(MDS). It’s a precursor disease to Acute Myelo Leukemia(AML) and MDS will progress into AML with 100% certainty.  It seems that Maya (again, the special child) is in the 3% of children who ended up with secondary cancer due to the therapy she’s received.  It could be a variety of the chemo she’s received, such as doxyrubicine, cisplatine or etoposide. Indira believes that MDS is the result of the MIBG treatment that Maya received in St. Justines this past January.  Who’s to say?

Dr Baruchel from Sick Kids was kind enough to arrange the bone marrow aspiration as well as provide us with the initial consultation on what MDS means.  Suffice it to say that it was a sobering discussion not unlike the first news of neuroblastoma for us.  The main difference now I guess is that we understand what “challenging” and “difficult to treat” really means.

So what does it mean to have t-MDS or t-AML?

• It’s difficult to treat. It is believed that treating t-MDS has a bit better outcome than t-AML.
• t-MDS will progress to t-AML.
• The only known potential”cure” for t-MDS or t-AML is Bone Marrow Transplant.

We’ve been through a bone marrow transplant.  And we almost lost Maya to one of the complications called H-VOD (Hepatic Veno Occlusion Disease).  It is a brutal therapy.  Our biggest concern is whether or not Maya will be able to tolerate a second BMT.  Even if we ignore the long term damage that we are putting Maya through, the fact is, we don’t know if Maya will be able to handle the principal assault again. Children do die from complications from BMT.  But then, not to consider the therapy means Maya will not survive the t-AML at some point. It has not been an easy couple of weeks, as we’ve been learning about this new challenge.  Will we be burying Maya within the next year?  Damned if you do and damned if you don’t.  It’s hard not to personalize these stressful events.  What did we do that was so wrong…

And this unexpected turn of events came just when Indira and I thought that we were seeing the light…  Somehow, we thought that we could make it!  With DFMO, we actually convinced ourselves that Maya could be well.

So… now we’re in Vancouver. We’re going to Sunshine Coast for a couple of days.  I think we’ll be doing some crab fishing, some Kayaking.  Then, we’ll head over to Vancouver Island.  I believe we’ll be going deep sea fishing for Salmons and Halibuts.  Time to get in the side car for the ride… and there’s no dining cars on a motorbike!

I hope Haida Gwai and Alaska will wait for Maya.

[Edit]  Some photos from the James Fund Neuroblastoma Family Retreat

It’s been an interesting week, this past one. Not one which I would like to repeat. In the past two 1/2 years, we’ve learned a lot about cancer.  After all, it has become the central theme in our lives.  It has also become part of many of your lives as you have followed us through our journey. Shall we say that we’ve become comfortable? Perhaps not comfortable, but used to it.

Having to deal with MDS has certainly mixed thing up.  Neuroblastoma seems so… yesterday.  We know nothing again.  And so, the researches have begun again. One major difference is neuroblastoma is a pediatric cancer. MDS/AML is (to be grossly general and possibly inaccurate) more of an adult disease. In other words, there is very little literature on pediatric secondary MDS/AML.  To put things in context, consider that:

• neuroblastoma hits 1 / 100 K kids.
• 2 to 3 % of children will develop secondary (therapy induced) cancer.
• So,  we’re talking about less than 2 or 3 children out of 10,000,000 kids develop MDS/t-AML.
• These are incredible odds, in line with winning a 6-49. I think the odds for 6-49 is 1 / 14 M.
• Yes, Maya is a very special child!

In this not so brave new world, blood is what’s on our mind. Specifically, we are focused in the white blood cells and platelets.  White blood cell and the immature white cells (blasts) are of concern to us.  It will increase and over crowd the bone marrow as MDS progresses into AML. The marrow becomes compromised as a consequence. Maya is not producing any platelets and hence CBC and platelet counts are what we now focus on.  Neuroblastoma has taken a back seat for now.

This past Thursday afternoon, after getting a CBC done at sick kids, Dr. Cada asked to speak to both of us immediately. We arranged a meeting expecting the worst.  And the news came to us as a big surprise.  Maya had approx. 40% blasts  in her blood.  By definition, 25% blast in her blood (AKA peripheral blood) is classified as AML or in our case t-AML.  The marrow failure team (sub-umbrella of Haemotology group) was quite concerned at this spike and classified Maya now, as having progressed to t-AML in a rather dramatic fashion. Typically, MDS does not progress so acutely.  The implication was that our plan of keeping Maya on Vidaza was now off the table and the only course left to us was a BMT… if BMT team thought that the second BMT might be beneficial for Maya.

Until Friday afternoon, an offer for a second BMT was not confirmed.  This news was a complete shock to us.  How can she look the part of a healthy child, yet be so, so sick? In order to confirm the progression, an emergency bone marrow aspiration was requisitioned for Friday morning. Maya underwent another BMA in a week.

Indira and I had a very disturbed evening Thursday night.  The only course of action left to us is a therapy that may kill Maya.  Indira and I decided that Maya, as per her wish should have an early birthday party.

Friday afternoon, it seemed that most of the Oncology/Haemotology team met and discussed how to proceed with Maya. As Maya was the first child for BMA, by the time that the team met, some of the BMA results were available for the team discussion.  Subsequently, we were given the summary of the team meating. Our meeting was represented with two marrow failure physicians, BMT physician (One of my fav… she’s just awesome) as well a couple of nurse practitioners and the social worker. So, here we were, surrounded by a small regiment of sick kids staff.  Being surrounded by so many clinicians is not something to look forward to.  We expected them to confirm the progression and the discussion to be about how to proceed with BMT.

But, this is not what happend! It turns out that on rare occasion, marrow will dump out a colonal mass of blasts into the peripheral blood. This result is of concern, but in Maya’s marrow, the blast count was found to be 17%.  In other words, we are not classified as a t-AML patient.  We are still MDS. The results were infinitely better than what we anticipated.

Both Indira and I had dipped into our respective hell for 24 hours. We haven’t been so shaken up since the early days of neuroblastom therapy. While we appreciate the immediate response from Sick Kids, and it is really the right thing to do, believing that we were now dealing with t-AML was one of the most stressful period we’ve had in a long while.  As we were all gathered in one room, we took the opportunity to ask questions and have a frank discussion.  Here is the summary:

• 40% blast in Maya was very worrisome.   The only way to confirm is through a bone marrow aspiration.
• BMA blast count was found to be at 17%.  Therefore, we are still MDS.
• BMT team is willing to consider a second transplant.  The conditioning regiment (high dose chemo agent) is still to be decided.  Busulfan and Melphalan is still on the table as an option, with use of defribotide in the prophylactic role.
• No matching donor was found.  Therefore, the only option is to either use Maya’s own stem cells:
  • We can use the peripheral stems cells which we’ve collected from the first BMT.  We still have a lot left from the first transplant.
  • We can also use the cord blood stem cells which we’ve banked when Maya was born. Use of cord blood stem cell is thought to be the best option at this point.
  • We can use Indira’s blood in a haplo transplant.  We then would need to deal with the possibility of “Host Vs. Graft” disease. Mother’s blood does better in a child.    Not a big surprise, since Indira carried her in her body?
  • The main concern with using Maya’s stem cell is whether there is a predisposition for Maya to relapse.  In other words, is Maya genetically predisposed to leukemic diseases and this is why Maya developed AML?  If this is the case, using her own blood (autologous stem cell rescue)  would not be advisable.  If Maya is predisposed, haplo transplant from Indira would be the next best option.  While we are testing for leukemic predisposition, the results won’t be available for another couple of weeks.  Had Maya progressed to AML, autologous BMT would not be advisable as the possibility of relapse would be significantly higher.
  • Bone Marrow Failure team at Sick Kids like to proceed with BMT rather than wait.  And should we give our concent, BMT is ready to proceed.

Dr. Tal, BMT physician was kind enough to talk to her colleagues about Maya last week at the COG conference. So, we do have collective knowledge of the bone marrow oncologists across the world.  So, this additional information will be helpful to us. However, I requested a bit more time so that I can follow up on AML research.  Land mines are everywhere.  Our response to the doctors were as follows:

• Frankly speaking, there’s very little exposure at sick kids on t-AML.  For that matter, there hasn’t been enough cases of pediatric t-AML around the world to build a significant knowledge base.
• If there are centres that have dealt with more cases of t-AML, we would like to talk to them and possibly have sick kids refer Maya to this centre. The gravity of our circumstances warrents physicians with theoretical understanding versus “medical art”
• One centre that may stand out is Saint Judes in San Diego. They seem to have more clinical trials in leukemic diseases.  It is also one of the centres where our BMT doctor will talk to this coming week.
• We will convene next thursday to discuss treatment options.

Our thought presently is this:

• BMT is the only curative therapy.  It is also very high risk.  There is 45% and 40% change of complete cure using autologous and allogenic stem cell rescue is used, respectively.  If there is a relapse?  Third BMT?  I don’t believe Sick Kids would agree to it.  I don’t think we would either.
• Vidaza can keep MDS in check for some period of time.  However, one does not typically see any response from the use of Vidaza until 6 – 12 rounds, which translates into 6 – 12 month cycle.  So, we would not really know if Vidaza is working for a while.
• Use Vidaza:
  • does not work.  Full stop.  Goto BMT.
  • MDS is stable. stay on Vidaza until we start to see progression.  Goto BMT.
• BMT
  • It works.  Maya is cured of t-AML. Proceed with DFMO, if this treatment option is still available to us.
  • It does not work…

What we’re looking at is the optimal time frame when we should apply the treatments. Here’s an example.  Suppose Vidaza keeps MDS in check for 12 months for Maya. Going into BMT now rather than use Vidaza would mean that we’d be taking 55% chance of shortening Maya’s life to a couple of months.  Complication may kill her within 2 – 4 weeks of starting BMT. It’s too significant a risk to take.

We will need to look at the details still.  After all, the devil is in the molecular level details. We will have another follow up meeting next Thursday to discuss a plan of action.

With the scare of our lives behind us, we decided to go to James Fund Neuroblastoma Family retreat.  Taylor came with us, this time around and we all had a great time.   Being with the families who deal (past and present) with this aweful disease is … cathartic in nature.  They, we, all understand the tribulations we all face in multiple dimensions.

This weekend, we had a lot to be thankful for.  Thankful to Syd and Diane (James Fund), the volunteers, the families, the camp but most of all, we are grateful to have the kids really enjoy themselves.  Picutures will be posted soon.