Appointment Set & Gene Mutation Confirmed

It's been so long since I've blogged, that I forget where I left off!  Last week was so busy!  On Wednesday, March  11, 2015, I was called in to substitute teach.  When I got home, Todd told me that he had talked to the bone marrow transplant doctor in Cleveland and that they had the rest of his bone marrow biopsy results back.  The result we needed the most was the confirmation that he still had the IDH2 gene mutation, that qualified him for the AG-221 drug study.  Unfortunately, they told him that there was not enough DNA from the biopsy to complete the test!  We waited two and a half weeks to hear this!  His cytogenetics did come back showing just the one same 5q chromosomal deletion as his first biopsy post-transplant.  This was good news, but the doctor still did not think that the medication Revlimid used to treat patients with this single 5q deletion would work, because he had multiple complex deletions prior to transplant.  The problem with attempting to treat Todd's cancer with this drug right now is that it ONLY treats this one deletion.  While it could wipe this one out with constantly taking the medication, it won't prevent the other deletions/chromosomal abnormalities from coming back at any time.  This would be a waste of valuable time and somewhat counter-productive.

His BMT doctor thought it would be a good idea to see if his oncologist at Cleveland, who originally ran the DNA testing that discovered the IDH2 gene mutation, might still have a sample left of his marrow.  So, she recommended calling him to see what he suggested.  This doctor was Todd's main oncologist/hematologist prior to transplant.  We got to talk to him shortly afterwards.  He gave us recommendations of other doctors in the field that he trusted because of their experience.  One was at Northwestern in Chicago where they are conducting the trial study; another was at MD Anderson in Houston, Texas, also doing the study; and a third was a former fellow and student who now works at Memorial Sloan Kettering.  He knew of Dr. Stein and informed us that he and any other doctors assigned as the primary investigators of the study were being paid by the drug company Agios who is conducting the studies.  (This is called full disclosure).  We knew this, but in my search without a recommendation in Nashville, I called Dr. Stein's office anyway, because at least he was familiar with the drug and its results.  He told us that Dr. Stein was young and that we may want to consider a doctor who has been in the field longer, but that we should go wherever we could get in first!  Just because we sent records did not obligate to keep an appointment.  He also confirmed that it would likely be at least a month or two before the drug study would be at the Cleveland Clinic. 

When we asked about the Todd's former bone marrow samples, he said he had them in a freezer, but that whoever does the study would probably want a recent result.  He recommended our local oncologist collect a sample of peripheral blood cells to send to special lab in California to get the DNA IDH2 gene mutation results from that.  They took this sample last Thursday and I called to follow-up that they sent it to the right lab.  (Ugh...)

So, we started looking up names and phone numbers of places and doctors to call.  First, we had to confirm with the insurance company that these doctors and hospitals were in-network.  We have learned that routine blood work and other tests will not be paid for by the drug company during the study, so it is important to make sure you have coverage for the incidentals.  All three recommended doctors were in-network. 

Next, I called the doctor at Northwestern in Chicago since it was closest.  Unfortunately, the doctor would not be able to see us until April 1, 2015, which I thought was too far out.  Then, we called MD Anderson, but before we could schedule anything, they had to get our insurance information and process a request for coverage.  Since then, we have been playing phone tag, with no appointment scheduled yet. I tried to call them again today, but they refused to talk to me, stating that they had to talk to Todd first to get permission to talk to me.  We went round and round for ten minutes; I tried to hand the phone to Todd during his blood transfusion, but we can't get a signal in his ATA room and of course, the call was lost. (I had been standing in the hallway).  MD Anderson might be the #1 ranked cancer hospital or whatever, but I'm not impressed with their scheduling and staff!  Who would even want to go there after all that? 

While all of these calls were going on, Dr. Stein's office called and asked for a special request that Todd's pathology slides be sent to him by an express delivery service.  I told her we didn't get the results back from the biopsy confirming the DNA, but she assured us that Dr. Stein could always perform a bone marrow biopsy at the appointment.  So, I called both the local oncologist's office and Todd's BMT doctor in Cleveland to get the necessary records sent to MD Anderson and the slides to Dr. Stein. 

The next day, I called the Corporate Angel Network about arranging a flight to New York for the appointment on Monday, March 23, 2015 at Memorial Sloan Kettering with Dr. Stein.  They were able to take down all of our information and get Todd registered for a flight.  They told us that they could NOT guarantee us a flight for that day, so that we would need to have a "back-up plan."  She asked us what our back-up plan was, and I said driving I guess!  We told her we could return the same day, but she said most flights leave in the mornings, so that means we will have to get a hotel room for the night.  Since then, we talked to our pastor when he came to the house to visit, and he advised us NOT to drive into New York City.   That it was extremely difficult and parking too cost prohibitive.  Unfortunately, buying two last-minute plane tickets will also be cost prohibitive. 

The Corporate Angel Network is supposed to notify us 24-48 hours ahead of time if they were able to secure a flight for us.  I need to start working on a "back-up plan." I can call the other flying services for cancer patients and/or our pastor said he knew someone who was a pilot who may be available.  Today, our local oncologist told us that some airlines are willing to sell discounted airfares to cancer patients for appointments with some kind of doctor's note.  We could try this or just cough up the money (what's a little more debt?).  If none of that works, we hope to have a second appointment secured somewhere else.  (Looks like it won't be MD Anderson).  I'm thinking about calling back to Northwestern in Chicago and seeing someone else or just taking the April 1 appointment if it is still available.  At this point, I am going to do whatever it takes to get him in somewhere else!  And if we aren't happy with the opinion of the doctor we see next, then we will keep going until we are.

Todd's counts were not good last Thursday, March 12, but he didn't need any transfusions that day because his hemoglobin was at 8.1.  We would normally feel happy about this news, but not that day.  Todd had already felt run down and not getting a transfusion then meant having no energy until they could get blood work again on Monday, March 16.  His platelets were good, but his ANCs and white counts were "non-existent."  The nurse had me a bit scared and went to talk to the doctor about having his Hickman catheter removed (because they can be a magnet for infections), but we did not agree with this.  His Hickman looked good and he wasn't having any problems with it.  It makes transfusions and blood work so much easier on him that having to poke his arm which takes weeks to heal.  They did caution us though to take his temperature often throughout the day.  They told us that the guidelines for fevers had changed from calling with a temperature of 101.4 or higher to 99.5 or higher!  This also seemed overkill, because he had been running a low grade fever off and on.  We understand the risk of infection, but felt that running him to the hospital for a low grade fever only exposed him to more infections there than at home.  So, throughout the weekend, we took his temperature about three times per day.  If his fever went above 99.5 we waited 30 minutes and took it again.  If it went up or stayed up then we agreed we would call, but we didn't have to.  His fever did get up to 100 but only when he had been sleeping in the warm bed.  Once he got up, it went back down to under 99 degrees. 

We were due to see the doctor and have his blood work done this morning, Monday, March 16, 2015.  His hemoglobin was at 7.3 which was low enough to warrant a transfusion (<8.0).  His platelets jumped up to 70,000! But, his whites were still barely on the radar at .2. 

Here we sit, once again in the Advanced Treatment Area (ATA) of Miami Valley Hospital getting his two units of blood.   I pray it will energize him for several days.

For some reason, he is still scheduled to return to the Cleveland Clinic for treatment and to see his bone marrow transplant doctor this Friday, March 20, 2015.  I guess it is part of his monthly post-transplant check-up, but I hardly see the point, except that it will give us the opportunity to talk to his BMT doctor face-to-face and to get his breathing treatment of Pentamidine (anti-fungal) to prevent any lung infections or pneumonia.

Post script. The blood work taken last Thirsday confirmed that Todd has The IDH2 Gene mutation.  So we are good for the study!  Now we need to pray for the airfare or positive response from Corporate Angel Network 

The year ends with Transfusions.

We had to get up at 5:00 this morning to be at the Cleveland Clinic by 9:15 am. As we got closer to Cleveland we see what looks like mountains in the distance. Of course there are no mountains...it's a huge cloud bank covering Cleveland. How typical!

We arrive and they quickly get to the blood work, including a new chimerism study and type and screen anticipating the need for transfusions. Todd was feeling pretty fatigued the past few days and we knew his hemoglobin was down last Friday. The results came in that he needed platelets. His was 9 and the threshold is 10. He also needed two units of blood since his hemoglobin was at 7.6. and the threshold is between 8 and 8.5. His white counts were up to almost normal at 3.47 or 3,470 which is likely the result of the Vidaza chemotherapy giving him a bounce. 

Todd teased that he knows how a vampire feels when he hasn't had any blood!

Our social worker stopped by to give Todd the standard 100 day post-transplant survey. She has been such a great help!  

Todd's regular BMT doctor was back from vacation and we had a good long visit. She took him off all of his maintenance medications except for one, his Acyclovir. This made Todd happy!   After discussing today's counts she talked a little bit more about where Todd is and a likely game plan for the next few steps. 

First, he will have his next round of chemotherapy in Dayton starting January 12, 2015. She said she only wanted to do 5 days of the chemo Vidaza instead of the standard 7-day treatment regimen he had over the summer, because his bone marrow is still very sensitive to any changes and they are exposing both his diseased marrow and his brothers donated healthy marrow to the toxicity of the chemo. While they hope to kill off his original diseased marrow they don't want to damage or lose any of his new marrow. 

She would actually like to do at least two more rounds (Jan and Feb)of Vidaza chemotherapy to get Todd back into remission enough to proceed with a second stem cell transplant. But this will have to be evaluated week by week and month by month. Many of these decisions will have to be made based on how his chimerism stays. If his brother's donated marrow can hang in there, they can proceed with additional rounds; but, if there would be a drastic change where his original marrow would increase to the point of wiping out his new marrow, then they would likely have to stop the Vidaza and start some type of stronger chemotherapy, like what he had to wipe out the marrow before his transplant. 

Right now, his chimerism consists of: His own original marrow 60% and his brother's donated marrow at 40%.  There is still a hope that the Vidaza can target the diseased original marrow, causing it to decrease, and allowing Tom's donated marrow to flourish.   She said the likelihood of Todd developing any Graft versus Host Disease at this point is minimal and not likely.  So, he won't be able to utilize the Graft versus Leukemia Effect to wipe out his old marrow, which is what has made the first transplant unsuccessful.  

We talked about the possibility of using a different donor this time instead of his brother Tom again.  I asked if there was a possibility that their HLA Match was "too good," not allowing any Graft versus Host, but she said it is complicated to bring in another bone marrow from a third person when he already has two different marrows.  She explained that Todd's marrow is not only sensitive because of all the chemotherapy and the transplant but because they are co-existing. To add a third person's marrow may create a range of other issues including exposures the new donor would bring in.  So, that option is not ideal right now.  

She is still waiting to see what would work best when harvesting Tom's peripheral blood stem cells.  There are two main options.  The first would be to give him Neupogen injections prior to harvesting, which would produce a larger number of cells, but they would be newer, immature cells that may not be as effective depending on the situation.  Or, the second, to harvest the stem cells without Neupogen, because then they would be able to obtain more mature cells.  Either way, it looks like we are at the mercy of Todd's brother Tom to donate blood stem cells.  This is much less invasive than donating bone marrow.  He would only need to do a pre-blood screening prior to donating and it only takes several hours to sit and filter his blood for the cells.  

As to whether the second stem cell transplant can be done outpatient or inpatient is yet to be determined.  Too many factors to consider now.  This is another decision that needs to be made closer to the transplant.  

As for going back to the Cleveland Clinic for treatment appointments and transfusions, we no longer need to do that.  Todd is going to start going to his local oncologist here in Dayton to have blood work drawn every Monday.  If he needs transfusions, it will be arranged here in Dayton at Miami Valley Hospital again.  So, this is good news for us.  We will only need to go back every few weeks to have blood work drawn for special studies and to meet with his doctor.  

So, the next appointment in Cleveland, will be on Wednesday, January 21, 2015.  Hopefully, he will have his next appointment here at the local oncologist on Monday, January 5, 2015. (It's been hard to get things scheduled with the holidays and reduced staff).  Then he will start his out-patient chemo here the following week, Monday, January 12.

I feel pretty good about this game plan.  I did ask about any clinical trials that he would be ideal for, instead of doing the second stem cell transplant, just to make sure we were looking at every option.  She said she could look at that route, or the option that Todd could just stay on the Vidaza month-to-month until he stopped responding to it.  Then, they would have to try another medication, like Revlimid, which has showed some success with patients who have just a 5q chromosomal abnormality, but this wouldn't be guaranteed to work, since Revlimid works better on patients who have only had this deletion in the past and not the complex multiple deletions Todd has had in the past.  She said we would lean towards these options if Todd was older and in poorer overall health, but, since he is young and in good health right now, she feels the more aggressive treatment of the second stem cell transplant is a better course of treatment for him.  Todd does face the risk of getting a bad case of Graft versus Host Disease, which she said he doesn't want, so it will take some serious finessing to get the chemotherapy and immunosuppressant use, both prior and post-stem cell transplant as fine tuned for him as possible. 

In addition, she reassured us that she alone would  not be making all the treatment decisions, but that she would be relying on her colleagues in their weekly meetings to give her their perspective and experiences in planning a course of action.  It is nice to see that she doesn't have a "God complex" and that she is humble enough to listen to the opinions of her colleagues.  

I still might look at other options or see what clinical trials are available on my own.  However, I can't help get past the stigma in my own mind that clinical trials are for lost causes.  

Looking back, I wish we had made the decision to have the transplant prior to him developing the complex chromosomal abnormalities.  This was a hard decision to make then without having the hindsight we have now.  His blast counts were staying under 10%, no where near the Acute Myeloid Leukemia level (20%) and he went from two years of having no abnormal cytogenetics to having multiple complex chromosomal abnormalities 3 months later.  I think the "wait-and-see approach" was alright for awhile, but once his numbers starting climbing, we shouldn't have risked the chance of him developing chromosomal abnormalities.  It was this development that convinced me to push him for the transplant, knowing that it can alter a patient's prognosis.  I personally believe that these abnormalities are complicating treatment now and have contributed to the unsuccessful bone marrow transplant.  But, this is just my "hunch" and I don't have empirical, definite evidence to prove that.

Looking back, however, while it might help or influence someone else's future treatment decision (that is the only reason I include my opinion here), doesn't help us at all.  We must look forward, remain positive, and trust God with the future.  I'm learning from the book that I am reading, that the only thing that separates a Christian from a non-Christian in situations like this, is in how we respond.  Christians have no extra protection from cancer from non-Christians.  If it is God's will to allow cancer, then he must have a purpose in the process and/or outcome.  Maintaining our joy and trust in his divine purpose through this crisis can bring us comfort and provide hope to others. 

In closing, I read something recently that said when a loved one has cancer and is going through treatment, it is important to view your current state of uncertainty as the new normal.  This is going to be my outlook in the new year. God Bless!

Day +87: Chemo scheduled in Dayton

We learned today that Todd will be able to do his outpatient chemotherapy with the local oncologist in Dayton starting Monday, December 15, 2014 for five days. This is great news. The only downside is that if his blood counts are low, he will have to go to a local hospital for transfusions. But, this is still better than spending the whole week in Cleveland. 

At today's treatment, Todd ended up needing a blood transfusion as his hemoglobin had dropped to 8.1. He has been very tired, so I hope this will help with his energy level. 

The other counts were down also. Whites were at 1.28 or 1,280. Low white counts can make him more Susceptible to infections. His platelets were high enough not need a transfusion, but they too continue to drop: 22,000. 

We are so grateful that we can be home next week. Driving up and back to Cleveland two times per week is getting tiresome. We have to get up at 5:00 am to get to his appointment on time. But still, this is better than staying in Cleveland all week. 

We have thought about what went wrong with the transplant: Why it didn't wor.k. Todd thinks they didn't give him enough chemotherapy to wipe out his bone marrow, but I think the problem lies in the use and application of the immunosuppressants. They chose to suppress his brother's donor marrow so he wouldn't get a bad case of Graft versus Host Disease, but I wonder why they didn't suppress Todd's bone marrow and let his donor marrow grow and engraft unsuppressed. I guess this was the professional decision of the doctor who is the specialist in this area. 

Whatever contributed to the failure of the transplant (we may never know), our eldest daughter in her wisdom told us: Don't regret the decision to do the transplant. It was the only curative treatment and we had to try it. The odds were in our favor. I have taken comfort in this truth. We can't change the past or second guess the decision to transplant. We can only move forward taking life day by day and make the best decisions based on where we are that day. 

Thanks for your support and prayers. We still believe God can perform a miracle in Todd. 

Day +66: New Bone Marrow Not Engrafting; risk of Transplant failure

Todd's treatment appointment today, Friday, November 21, 2014 started out a bit disappointing. His blood counts have not been going up like they should. As a matter of fact, they have dropped. His whites went down to 3,080; his hemoglobin to 10.6, and platelets down to 37,000 (a few weeks ago they were up to 58,000).

Then the doctor called us about 5:00 p.m., while we were driving home from Cleveland with the results of Todd's latest chimerism numbers from the blood tests they drew on Monday.  More bad news. Instead of his original bone marrow going down to the 0-5% they need to be, they went up!  To refresh every one's memory: The day he left the hospital (October 8) his original bone marrow was at 49% and his newly donated bone marrow was at 51%. The next set of results at Day+49: Todd's original marrow had dropped to 28% and his new marrow increased to 72%.  These results were slow, but good. At least they were headed in the right direction. This week's results:  Todd's original marrow went up to 50% and his new marrow decreased to 50%.  This is not what the doctor had expected.  This is a serious indicator that his newly donated bone marrow is not engrafting. Instead, his original marrow is growing back and taking over.  This may lead to a bone marrow transplant failure.  In this words of his doctor, this is not a rare occurrence, but it is not the common result, which should be full engraftment (New marrow at 95-100%). 

So, what does this mean?  That's what we are unsure of.  Unless they can get his original bone marrow to go back down and his newly donated marrow from his brother to engraft, Todd will likely relapse and have to have further treatment. 

While this development can be fatal if it happens earlier after transplant, this isn't the case at this point.  In that situation the body thinks the new marrow is a foreign invader and tries to kill it not knowing that the chemotherapy would have likely wiped-out all the original marrow, leaving the patient with no marrow and therefore no way to make blood cells.

What's likely happening now in Todd's case is that for some reason Todd's body may have developed some kind of anti-bodies or resistance against the new marrow and is attacking it and taking over (or many other possible reasons that are too technical to understand and explain here).   At least Todd's original marrow is producing some blood cells and the new marrow is producing the other half the blood cells.  The whole purpose of the intensive chemotherapy was to kill Todd's marrow which is not healthy, cancerous, and can't produce enough mature healthy cells.  The purpose of the transplant was to replace the bone marrow that would produce new healthy blood cells with normal blood counts.  If this doesn't occur it is considered a Bone Marrow Transplant failure and can result in a relapse of his disease: MDS.

There are several things that can be done for Todd, but at this juncture, the doctor is opting for the simplest solution: to ween him off  the rest of his immunosuppressant medication (Tacrolimus).  Last week his doctor changed his medication from 4 capsules per day to 3, because his numbers had dipped some.  Tonight, she told him to cut it down from 3 capsules per day to just 2 per day.  She will likely drop them down again next week when we go back.  She said there is still hope that this will allow Todd's body to develop some Graft versus Host Disease to suppress the existing original bone marrow and allow the new to engraft. (See posts on Graft versus Cancer/Leukemia Effect).  So far, Todd has been doing great, maybe too great.  He has had little side effects, little to no symptoms of Graft versus Host Disease, no rashes, no digestion issues, no severe eye dryness, no infections, etc.  He needs some for the Graft versus Cancer Leukemia Effect to work.

This is where God comes in and how you can help!  We desperately need your prayers, that this simple reduction in medication will be the answer to this problem.  This is a critical time.  This needs to work in the next few weeks or it may be back to the drawing board for other, more difficult solutions. 

To gauge how the re-development of the former marrow is effecting his counts, his doctor has also suggested moving up the post-transplant bone marrow biopsy from the +100 check-up point to about Day +80.  She wants to see if the re-growth of his original bone marrow has developed any cancerous blast cells.

To think about the possibility of further re-treatments after everything he has been through is just too much for us to wrap our heads around.  The possibilities could include: another transplant of his brother's stem cells with another new 100 day period of watching and treatments; a new round of different chemotherapy and another transplant from his brother's cells; or another round of chemo and/or transplant with an unrelated donor's cells with the same 100 day follow-up.  I'm trying not to worry about these possibilities and neither is his doctor. 

While it has only been +66  days since the initial transplant, we were in Cleveland for 8 days before that.  Todd spent 31 days in the hospital, endured intense chemotherapy, isolation, nausea, diarrhea, fatigue, lack of appetite, and lack of friends of family.  I have spent around 68 days living in an hotel room/suite, driving to the hospital for 12-14 hour visits or some days overnight visits, away from our home, our three daughters, friends, family, and yes my dog!  Our children have had to be away from their parents and worry about their dad, my poor mother had to be away from her home and my dad while trying to fill my shoes all that time (a job well done, but not for the faint of heart).  Todd and I have had no ability to work or earn an income but instead have had multiple households and expenses to pay for. The thought of doing this again would be too difficult to put into words here.

I guess we will learn more on Monday when we go back to see the doctor.  They will draw blood for another chimerism study in addition to checking his regular CBC counts.  We are blessed that the dropping counts have not yet resulted in the need for any transfusions. 

In the meantime, will you pray?  This journey has been full of ups and downs and twists and turns.  I feel like God is asking us to let go of everything else and trust him completely.  I have been applying for jobs, with no response. The one job interview I had scheduled (for seasonal work) was canceled tonight because they had just finished filling all their openings.   I want to cry out to God: "Why we can't we catch a break!  Why are you allowing things to go wrong? Why are we suffering such financial losses and the loss of things that make us feel secure?"  I want to tell God that "No, I really can't handle anything else!"  But, I know he is trying to teach us through these trials to solely rely on him.

Next week is Thanksgiving.  I want to give Thanks for the lives of those I love and the good health that he has blessed us with.  I understand that every good gift surely does come from above.  Thank you Lord.