Day 2: Testing for Trial Drug AG221 in NY

We slept until about 9:00 am on Tuesday, March 24, 2015. We took our showers and strategized about where to eat at a good sit-down breakfast, but, before we could  decide, Todd noticed that Dr. Stein's office had called and left a voice message for him to call them. He was told that he blood results showed his hemoglobin was low  (7.0) and that he needed a transfusion. They wanted us to come in earlier than noon so they could work it into the schedule.

We grabbed some quick breakfast (muffin, coffee, juice, and yogurt) from the  cafe in our hotel lobby and headed to the hospital around 10:30 am. First up, we had to go to get the type and screen to order blood for the transfusion.  Then, we headed over to Dr. Stein's office, where we met with the doctor to sign the consent forms.  Once signed, we were able to ask additional questions.  I had just a few after yesterday's visit.  I asked for his opinion on the use of chelation therapy to reduce iron in Todd's blood.  He said, that he thought it interesting that local oncologists typically recommend it, but that he nor other oncologists/hematologists at larger cancer facilities do not.  He said that the research shows that the use of chelation therapy has NOT been attributed to living longer, but has side effects, and for this reason, he doesn't recommend it.

I also asked about adding his Pentamidine treatments back in.  Todd was getting this medication to help prevent a pneumonia caused by Pneumocystis jiroveci (carinii), but since we haven't been back to Cleveland, he didn't receive it this month.  We had met with the pharmacist yesterday, before seeing Dr. Stein, to discuss all the medications and chemotherapy Todd has been on.  It is important to document because using chemo or certain medications before the study or during the study, can disqualify him from the study.  There was some question as to whether he could continue this medication or if he needed to switch to a similar drug in pill form.  So, Dr. Stein clarified that he can have Pentamidine if it is inhaled only, which is what he has been doing.  He recommended we have it set up to be done by Todd's local oncologist.  I noticed though that they had it set up there at Sloan Kettering for next week just in case.

After finishing with Dr. Stein, we were reunited with his research assistant, who asked Todd some questions about his current symptoms, to use as a baseline for comparison after treatment of the drug begins.  Then, another assistant, took us under her wing and let us know she would be there to guide us through the day's schedule.  First up, was the echo cardiogram and EKG.  Next, we tried to fit in the blood transfusion, but he had to go get the bone marrow biopsy next.  It was probably after 4:00 p.m. before he could settle in for the transfusion.  I ran down and got us some "lunch" at the cafeteria.  Their procedures for transfusions are a bit different from anywhere we had been.  They wouldn't run the transfusion IV at full pump speed (240) after the initial 15 minutes.  The nurse said that since Todd was a new patient, they were being cautious and might have been able to run it at 200 if he had been there before, but that they never go over that.  So, running the blood at a speed of 175, it took about an hour longer than normal, or 2  1/2 hours for one unit.  At first, they were only going to give him one unit.  Apparently, that is the new standard unless the patient is lower than 7, but we argued that in all the times he had transfusions, he had never received just one unit.  So, the nurse called Dr. Stein and he approved the second unit.  He was concerned about Todd's oxygen levels in his blood, since he would be flying the next morning. 

Todd didn't finish getting both units of blood until 9:00 p.m.  Once again, we got take out and ate it in our room.  It was another long day, but Todd was feeling better.  We went straight to bed, because we had to be at our shuttle stop at 7:00 a.m. the next morning.  Everything went according to the schedule the Corporate Angel Network set up for us.  We arrived at Teterboro airport and flew out around 8:45 a.m. and landed in Columbus, Ohio around 10:15 a.m. We had to drive back towards home to go to two appointments, one at noon and the other at 3:00 p.m., so Todd could get his IV antibiotic treatment at the Cancer Center. 

We wanted to thank everyone who helped us with the trip: The Corporate Angel Network and their generous participating companies and Beau Townsend Ford, (especially Jamie, Chris, and Kevin) who paid for our hotel stay both nights and helped with medical bills that were not covered until we reached our deductible. 

What to expect next:
We are expecting to hear from Dr. Stein's office by this Friday, March 27, or Monday, March 30, 2015 to hear if Todd was approved.  His test results have to be examined and his case brought before the drug company's board and the Sloan-Kettering's board.  Once we get the call, we will return to New York next week, either Monday, March 30, or Thursday, April 2.  We will need some time to arrange flights, rides, and hotels.  We will need to return to Memorial Sloan once a week for the first month and then only twice per month or every 15 days after that.  We hope that the Cleveland Clinic will be an approved study location by then, so we can transfer his case study there, which would just require two trips up to Cleveland. 

Locally, he will finish out the last few days of his IV antibiotic treatments and then he is scheduled to see the local oncologist on Monday, March 30, if we are not going to New York.  They will also run a CBC to see how his counts are and order any transfusions if necessary.

Other news:
It was interesting that I was exploring reasons for Todd developing his MDS a few blogs ago, when the MDS Foundation posted a talk regarding this exact subject: http://www.onclive.com/onclive-tv/Dr-Komrokji-on-MDS-Risk-Factors-and-Preventative-Measures  While it is hard to hear everything the doctor is saying, because of his accent, the basics of his talk is written out.  So far, it would appear that smoking cigarettes is one of the main causes of new cases of MDS, because of the benzene contained in them.  (Todd has never smoked though).  If you are a smoker, can I beg you to find a way to stop?  I have watched three grandparents die from smoking related diseases and cancer. There is so much proven research out there that shows that smoking causes multiple types of of cancer. 

They also know that prior chemotherapies can also lead to MDS (like Robin Roberts from Good Morning America who had breast cancer first, and developed MDS from chemotherapy treatment). 

I have finished my semester classes, which will give me more time to work, care for Todd, and get our house ready to sell.  While I dread the idea of selling our house, knowing how traumatic and challenging it is going to be, we just can't afford to stay here.  If anyone is willing to help us do some house repairs or box-up things to move, sell, or donate, please let me know via email, Facebook message, or phone call.  We will also be looking for a 3-bedroom place in Beavercreek, OH to rent, if anyone knows of a suitable place. 

In addition, I have stopped looking for a full-time job right now, but I will be substitute teaching until the end of May.  I may look for something else part-time after school lets out.  It is really hard to plan anything as we seem to be living day by day or week by week.  But, both of the older girls are looking for summer jobs, if anyone can offer them something.

Thanks to everyone who has helped us with meals, rides for the girls, and I even received a gift card for a message, which I had asked for!  We appreciate your love and support. 

Appointment at Memorial Sloan Kettering

There is so much to say I don't know where to start and what to include in this post. 

First, I need to give a shout-out to The Corporate Angel Network. I can't say enough good things about our experience so far. I spent time on the phone last week coordinating the appointment, securing a hotel, and waiting to hear about flights. 

We got the call Thursday that they got us a flight into Terboro Airport, NJ leaving out of Columbus, OH. They arranged for a car to pick us up at the airport and drive us to our hotel into New York City. We had to pay for the trip/car but it was so nice to let an experienced driver navigate the narrow lanes, traffic jams, constant honking, and aggressive drivers. 

On Friday,March 20, 2015 we got a call that the Angel network had secured us a flight back on Tuesday morning, March 24, and a free shuttle ride back to the airport. We would only have to pay a cab to get us to the shuttle location before 7 am. The flight would return back to Columbus so we would be able to drive ourselves to the airport and leave our car. 

Meanwhile, in Dayton they wanted to  give him IV antibiotics for seven days so they had to schedule around our trip 

We arrived an hour early to the independent Flight company an hour early. It was so nice not to have to go through security, put our liquids in small bottles, and be exposed to all the people at a public airport. The pilots were so nice and made us feel welcome. The  company members, whose flight we were on with, were so gracious and hospitable to us. The flight from Columbus only took 1 hour!  We landed and our car arrived shortly and took us to our hotel, The Bently, in the upper east side of Manhattan, which is only four short blocks from the hospital. We didn't have time to go to get food at a restaurant, so we grabbed a bite at the hospital's cafeteria. The appointment was at 2:00 pm. 

The space inside the hospital was very tight, which makes sense for a prime real estate area in New York. The staff were all extremely friendly and accommodating. I also liked their policy of asking everyone to wear masks, including family members in the Cancer office waiting rooms. They also provide rubber gloves for patients who don't want to touch anything. 

We didn't have to wait long to see Dr. Stein. He wasn't anything like I thought he would be. He was short, friendly, personable, honest, and straight-forward. He asked Todd to recount his medical history from the time of diagnosis in October 2011 to present. Then he gave us the opportunity to ask questions, which I had a list of!  

I started with asking him about his opinion to do a second transplant or not. He said it doesn't matter whether to do the second transplant now or in the future. He felt that Todd would still have the same results. He asked us if we were aware of second transplant outcomes. I said yes, they weren't good. He said that's right. According to the published reports, second transplants have a success rate of 5% to 10% and he felt those numbers were generous. 

I asked if Todd would be a good candidate then for the study and he said so far everything looked good. I also asked if there would be a better study out there besides this one, and he said no.  For Todd's MDS with the IDH2 gene mutation, this was the right one. 

We asked if we could start the study here and then transfer to another closer study location and he said yes. According to his sources, Cleveland might be up and running by mid-April at best. 

I asked if the drug was working for him, could he stay on it indefinitely and he said yes. They would continue to administer it to him throughout the additional phases of the study as long as there were no complications or adverse events (AE). Todd could continue transfusions and his current medications without any restrictions. 

When I asked about how often we would need to return for testing throughout the study, his answer surprised me; it was a bit more often than I had anticipated. The first month, we would be required to be present once a week. After that, every 15 days or twice per month. Testing on days 1 and 16 the first month would be the most intense with testing lasting 10 hours each day. He advised us to be prepared to stay an extra day afterwards to have some recovery time before flying home. 

When I asked the most important question: What could we expect from the drug that would help Todd and how soon he could start it, he began by saying that they are not sure how sustainable the response would  be. They hadn't got that far along yet in the studies.  So far, they have had patients still having positive results for as long as 14 months. He was clear to say that the drug should not be considered "curative."  He said the goals he would like to achieve in Todd's case would be to get his counts high enough to get him off of transfusions and to get his white count up past the point of being neutropenic. Blast counts at this point wasn't considered a major issue, since they were already low at 3%. The good news is that the drug can create healthy neutrophils from the blast cells, because it allows them to mature. 

He was very frank with us when I asked him what his opinion was regarding Todd's prognosis. Todd's BMT doctor just danced around the issue, and we wanted to know the truth. He regretted to tell us that relapsing within the 100 day period post-bone marrow transplant was detrimental and that Todd's only real hope for a curative treatment was the transplant. I cried and said why didn't the transplant work!  Everything was ideal going into it. I said I wish we hadn't done the transplant and it only seemed to make things worse. He assured us that we did the right thing in pursuing the transplant. There was no doubt in his mind that he would have recommended the transplant too, even if it was for a family member; he would have done the same thing.   It's so frustrating and hard not to ask WHY???

I asked him what was the difference  between staying on monthly rounds of Vidaza or doing the trial drug. He said that after looking at Todd's blood work, it didn't look like the Vidaza was really working. His platelets have come up but his other counts are still down. He also asked us if we know how sustainable Vidaza is, and we acknowledged that there would likely be a point where he would no longer respond to Vidaza. He agreed. In all fairness though, I had learned that it takes 4-6 cycles of Vidaza to reap the best benefits and Todd only had 3. 

With Todd's MDS, his blast counts have never been out of control or escalated to AML (>20%), but that's not what is affecting Todd's condition. Right now it's the low blood counts, especially his low white and neutrophil counts. This puts him at such a high risk of infection. As a matter of fact, he put it bluntly that for most patients in Todd's condition, infection is the most likely cause of death. The doctors are doing what they can to prevent this scenario by giving him antibiotics and antiviral medication. Monitoring his temperature is crucial. It is often the first sign of infection. If caught early, they can treat it more effectively. 

As to the costs, we are responsible for the preliminary screening, which our insurance should cover. Once he has been deemed eligible for the study, the drug company will pay for tests and treatments associated with the trial. In addition, they will help out with travel expenses up to a certain amount. 

So far there are at least 73 patients currently on the drug officially. It is a pill taken usually once or twice a day. We will be notified what amount and dosage Todd will take. When I asked about side effects he said that there have been some. Mainly an increase in bilirubin, but no major complaints of nausea or diarrhea. Among the AEs there have been some concerns with heart and lung problems. 

This is why they run all of the baseline tests: to establish how his organs are prior to the study and if there are any significant changes that could be caused from the drug. 

We asked how soon Todd could enroll and he said it takes about a week to sign, screen, and receive eligibility status. We asked if we could start by signing the consents that day, but he said no. Apparently, you can't see the doctor and sign the consents the same day. (Might look like Coercion). He asked if we could stay another day or two so we could get everything started while we were already here. We said we thought it could be arranged if they could do everything tomorrow. So his staff began to see if they could get all the necessary tests scheduled for the next day, while I called The Corporate Angel Network to switch our flight, and the hotel to see if we could stay another night. They got everything scheduled and so did we. I called my mom and asked if she minded to stay another day-it was fine. 

Before we left the hospital they needed to do a finger stick to collect a little blood to check his counts. Then he had to have a chest X-ray to look at his Hickman catheter. This protocol has to be done since Todd's Hickman was not put-in by Memorial Sloan Kettering. They have to ensure that it was done right and looked good before they are allowed to draw blood from it. 

It was rush hour when we left. We walked back to the hotel and Todd put on his PJs and took a nap. I eventually joined him. We napped until about 9:00 pm. We were too tired to go out so we ordered a true New York style Margherita pizza and had it delivered to our room. It was delicious. We watched a bit of TV and I flushed his lines and worked on the blog. We were looking forward to sleeping in, getting a hot shower, and getting a good breakfast since we didn't need to be at the hospital until 12:00 noon. 

In closing, We were sad to hear that our hopes for a curative second transplant were confirmed: not to pursue it because the rate of success would be very low. We were encouraged that we could start the process of getting enrolled so soon. Although the drug is not considered curative, we have hope that Todd will see an improvement in his counts and hopefully have more energy, and a better quality of life. There is still so much they don't know about the sustainability of the drug, or how long it will work, but we feel this is the best option for now. There is always hope that it will work for a long time, or long enough until another cure or newer treatment becomes available. 

I keep telling myself that miracles happen everyday!  It could happen for Todd. Thanks for your continued prayer and support. God is still in control of the big picture. 

Week in Review: Struggling to stay well

It's been a long week for Todd and I. We started off on Monday, March 16, 2015 with blood work and visit with the local oncologist. Todd's hemoglobin was below 8 so they arranged for him to get his transfusion at the advanced treatment area at Miami Valley hospital at 12:45 pm. Our nurse was great and she did her best to get us out by 6:30-7:00 pm.

The doctor asked about checking Todd's iron levels, because iron can build up in the organs after numerous blood transfusions causing damage. He normally treats iron build-up with oral chelation therapy. I told him what his BMT doctor told us: no they don't check iron levels nor treat high levels with chelation therapy because it was "controversial" in its effectiveness. The local oncologist was surprised to hear this. I explained that I think they thought it was mostly a secondary issue that was small in comparison to transplant problems. I did come across a great a talk given by Dr Azra Raza. DR Raza, Video 2. This video is the most comphrensive, but the other 3 are very short and also informative. I'm convinced enough to ask more about it and request his iron levels be checked.

The next morning, Tuesday,Todd didn't look or feel as good as he normally does after a transfusion. He had no pink color and no energy. I called off work the day before not knowing how he would be feeling. He got up and took a shower. I was in the kitchen with our eldest daughter home for spring break when I heard something fall. I yelled out if he was ok and when I didn't hear anything, I went running into the bathroom and found him laying on a towel outside the shower. I asked if he had fallen, but he said no, that he caught himself when he got light headed and tried to lay down on the floor before he did fall. I covered him up and started to dry him off with the towel and helped him into a chair. We got him dry and dressed and back into bed. It was so scary. He got up later and finished shaving but by that evening he still didn't feel well. 

I called the Dayton Cancer Center who had clinic after-care hours around 6:00 pm. They suggested we run him in to see the doctor on call. He wasn't running a fever at the time, but his blood pressure was 114/60. We went in and saw one of his oncologist's associates. They checked his blood counts and found the counts were about the same as Monday. So, he didn't need a transfusion but the doctor could tell he looked pale. He asked how Todd got MDS; he said he was technically too young to have it! That he must have been exposed to something. He asked if he played a lot of golf, because some golfers exposed to chemicals on the green could be affected. He said no. He worked long hours for most of his career and didn't have time for much golf. He asked if he had ever smoked, because they know for sure that Benzene exposure found in cigarettes and exposure to cigarette smoke or gas products can bring on MDS and AML. Todd never smoked and didn't think he was exposed to cigarette smoke overly.  This question is a rabbit hole that Todd finds irritating now. He doesn't know what would have caused the MDS, just like the doctors.  I had known benzene exposure was an environmental cause, but we never could find any relation. He finds this question annoying now.  Someone, somewhere has to be exploring the correlations and causes. Sounds like a good research study: to enroll people with MDS and AML, especially those with the IDH1 and IDH2 mutations, in a study where environmental exposures could be polled. Benzene can be measured in the blood stream but must be done shortly after exposure. Some kind of correlation may be established. Todd worked in the automobile industry along with two other patients we met while at Cleveland Clinic; one was a mechanic and the other was a general manager of a dealership. We were wondering if there was any correlation there, but one was a smoker, so it is hard to say.  Just thoughts...

They ended up giving him IV fluids the next morning, Wednesday, and sent him home. 

He was supposed to go to Cleveland Clinic for treatment and to see his BMT doctor on Friday, March 20, but after we got up at 5:00 am, he just didn't feel like it. I called and cancelled his appointments and we went into the Dayton Cancer Center instead   They ran a CBC and his hemoglobin was above the threshold so we went home. 

By Friday night, he still wasn't feeling well. So, I took his temperature and noticed it was previously 101.9. I was irate. I asked him when he had this fever and why he didn't tell me!  He laughed at me as I stuck the thermometer back into his mouth. We didn't have any Tylenol in the house, so he took an Excedrin Migraine tablet instead without telling me! He was still running a slight fever of 100.6. So I warned him how serious this was and he agreed. So I kept an eye on him and we agreed that since he had a sustained low grade fever for over 24 hours, that we would get up in the morning and go to the ER. 

When I called the doctor's office regarding his fever, they told us that they were open today for the Come Home Clinic and got us into them Cancer Center at 12:15 to run the blood cultures and urinalysis and see the doctor on call instead of having to go to the ER. We were relieved. After collecting the samples and cultures we saw a different oncologist in the practice. His fever was at normal then, but since his white counts were so low, they decided to put him on additional antibiotics: 7 days of IV antibiotics (Vancomycin), oral antibiotics and IV fluids. He slept most of the day Saturday and went back in on Sunday for the IVs. I wondered why they didn't put him on an anti-fungal instead, which is the standard drug additions from what I've read. http://www.uptodate.com/contents/treatment-of-neutropenic-fever-syndromes-in-adults-with-hematologic-malignancies-and-hematopoietic-stem-cell-transplant-recipients-high-risk-patients

Monday, we had the appointment schedule to see Dr Stein at Memorial Sloan Kettering, so he would have to resume The IV treatments after we return. 

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 

Pursuing a Second Opinion while tranfusions continue

This past week Todd had two appointments.  One with the local oncologist on Tuesday, March 3, and one solely for blood work on Friday, March 6, 2015. 

The oncologist appointment was uneventful.  We were happy that Todd's counts were high enough not to need any transfusions that day!  The oncologist just wanted us to update him on what the doctors at the Cleveland Clinic had suggested for Todd's next step in treatment.  He was unaware of the trial study drug AG-221, but after describing how it has worked so far, he was optimistic that this was a good choice. 

When Todd was getting his blood drawn by his regular nurse, she was anxious to hear the latest recommendations too.  We told her their decision, to pursue the trial drug study, and she began to tell us about a friend who too was proactive about researching her disease and possible treatments and had great success with a second opinion and treatment at Memorial Sloan Kettering Cancer Center in New York.  She also told us about a free flight program for cancer patients that took her friend to New York for treatment.  We brought this up to the oncologist and he told us that this was true.  The program uses corporate jets who are flying company executives to New York on business by offering cancer patients empty seats on their flight.  I went home and looked this up; actually there are several programs, but the one that his doctor and nurse were referring to is called Corporate Angel Network. 

I found this program along with the others on the Memorial Sloan Kettering Cancer Center's website under: Air Travel Assistance.  I have sent them an email and we are awaiting a response.

On Thursday, Todd had contacted his BMT doctor at the Cleveland Clinic to see if the other bone marrow results were in yet (including the much needed confirmation of the IDH2 gene mutation required for the study).  He received a message back saying that they had NOT come back yet and that the trail study in Nashville was not at Vanderbilt, but some research hospital there.  (I kinda guessed this when I was unable to find any information on Vanderbilt's website; and in Chicago, I could only find the study at Northwestern University).  So, this dashed my hopes of getting an expert second opinion at Vanderbilt. 

Todd had to go back to the Dayton Cancer Center on Friday, to have his blood counts checked again.  It confirmed what we already knew, he needed a transfusion.  Wednesday and Thursday had become increasingly draining for Todd and by Thursday afternoon, Todd didn't get out of bed.  His red count was just below the threshold at 7.9 and his ANCs and white counts were almost non-existent.  His platelets were up though around 56,000.  By this time of the day, almost noon on a Friday, the cancer center was NOT able to get Todd into the Advanced Treatment Area for a transfusion at either hospital: Miami Valley or Miami Valley South.  The only way for him to get his transfusion that day was to be temporarily admitted and put into a regular hospital room on the oncology floor.  Todd resisted this idea, and tried to side-step it once we got to the hospital, but they only sent us to admission and registration anyway. We both knew it was going to be a long day, but I have come to accept this.  I purposely did not plan on accepting any sub jobs for the day, anticipating this. I tried to reassure him that he was just going to have to suck it up and wait.  What was the alternative?  He would have maybe been able to get a type and screen done that day, and come back the next morning, but that would still end up taking at least five hours or more.  Plus, he would have been in bed the rest of the day Friday feeling so weak and tired, with no relief.  At least he could make himself comfortable, order dinner from the hospital menu, and get his transfusion done so he could start feeling better the next day.  After his transfusion, he felt extremely hot to me, and he did have a low grade fever of 99.9, which I was concerned about.  But, the nurse reassured us that this sometimes happens during or after a transfusion, and that he was allowed to take two Tylenol when he got  home.  He was about to get angry with him about fussing about the fever, begging me to be quiet so he wouldn't end up staying in the hospital for two days!  Instead, the nurse released us and told me to monitor the fever.  Oh, the grief the caretaker has to endure just because you are trying to do your job!

While waiting around in the hospital room that day, I decided to call Dr. Eytan Stein at Memorial Sloan Kettering, even though I had been delaying the call until we had received the final results back from Cleveland.  They were able to start a file for Todd, I answered all their questions, they told us which medical records were needed to be faxed, and anxiously informed us that the doctor had appointments as early as next Monday morning.  I told them that we wouldn't be ready to come that soon, but that I would get to work in requesting the necessary records from both sets of doctors here in Dayton and Cleveland. 

It ended up being a really long day (as always)!  We made it home about 9:30 p.m. and found my mom there playing Wii games with our youngest daughter. (Thanks mom for entertaining and feeding her!). 

We slept in late on Saturday morning and Todd felt well enough to have lunch with friends.  They could tell his energy level and spirits were much increased from the last time they had seen him.  I felt good that day too.  I felt optimistic that this study drug would be a good choice for Todd.  I pray it will be able to restore his blood counts enough to function without the need for transfusions, risk of infections, and eliminate his fatigue. 

But, for the meantime, he has been taking naps every day, which helps get him through the day.  I wish he had a better appetite, but I really can't complain.  I keep asking if I can get a current picture for the blog, but he usually responds like, not while I'm laying down! (Vanity still there! ha!).  

I was blessed to be able to work two days last week and I also received two calls for other jobs.  When talking with our friends and family, most have assured me to continue to trust God's timing and not push things to the point of just making things more messy and stressful.  Accepting a job that is not right for our family right now could be detrimental.  I knew just talking to Dr. Stein's staff the other day, that no one knows Todd's medical history, his counts, numbers, conditions, tests, or the research in the field better than me right now.  I'm in the best position to take care of him and its really where I want to be: by his side.   

P.S.  Talked him into it! 

AG-221 Trial Study: The Recommended Treatment

First, allow me to apologize for the delay in getting this post written.  At first, we needed time to take everything in.  Second, I began to suffer a severe migraine and ear ache for several days now, and was out for the count.  I couldn't focus on a computer, phone, or any reading the first few days.  I broke down and went to the doctor and got a message on my head, neck, and shoulders.  I am being treated for possibly TMJ (from clenching my jaw in stress) and a possible sinus infection, although the doctor thinks that my symptoms are mainly the result of stress.  (You think!) 

We received a call from Todd's BMT doctor Wednesday evening about 5:30 pm, February 25, 2015.  She called our home phone, which is unusual, and I walked in while Todd was on the phone with her.  He put the call on speaker so I could hear. 

She told me that she had conferred with her colleagues, the other bone marrow transplant doctors, and they came to the consensus that they were NOT in favor of doing a second stem cell transplant at this time.  We were a little shocked, knowing this had been her intent since December, 2014, once Todd's relapse was discovered.  Even now, she did not necessarily "agree" with this choice, but felt she needed to defer to the majority who would rather Todd pursue the trial study for the drug AG-221, because they felt like that would provide the best outcome for Todd, considering the aggressiveness of his disease. 

I knew from my own research, that the success rate for second transplants was not good, but I never wanted to discourage Todd, and after talking to his doctor back in December, we both agreed to be positive and hope for the best; that Todd was NOT a statistic, and that his case has not been textbook MDS from the beginning.  However, this ugly fact had to be considered now when determining his treatment options.

The doctors were not that impressed that his blast counts had been reduced from 7% at the time of relapse to his last biopsy which showed 3% blasts.  Because Todd relapsed within those critical 100 days post-transplant, and that after three rounds of Vidaza,  his disease was still present, they didn't think a second transplant would be successful.  This was devastating news all the same.  For the past three months, we had been pinning our hopes on this second transplant, and now they didn't think it had a good enough chance to work.  I asked why the change in that thinking.  She told us the success rates for second transplants with an aggressive disease was in the "teens."  I somewhat knew this, but had hoped Todd's case would be different.  He is younger and healthier than most of the patients who are in published studies; most are about 60 years old.  These odds are not very good, and they didn't want to set the transplant up for failure.  She said that with his chimerism at 75% of recipient cells (Todd's original bone marrow) and only 25% of his brother's bone marrow left, and with still have disease present (3% blast cells), they would have to do some type of intensive chemotherapy prior to the second transplant to suppress Todd's diseased bone marrow, for there to be any hope of success.  Then, he could get a bad case of Graft versus Host disease on top of the transplant not working, making his overall health condition even worse. 

She said that the only reason they do second transplants, even though the odds of success are so low, is that up until now it has been the only main option, apart from the Donor Lymphocyte Infusion (DLI), which Todd wouldn't be considered for, since his disease is still present (not an aggressive enough treatment).  But, now they have another option: The drug AG-221 in phase 1 trial studies.  The doctors at Cleveland collectively agreed that this drug would be Todd's best chance of controlling his disease.  It would NOT be the "curative" treatment, like the second stem cell transplant, but they have  had success with it controlling the disease and achieving "complete or partial responses."  This is the reason that his doctor was not in favor of the drug versus the transplant, because she said that knowing us so intimately, she wanted to go for the curative treatment. 

Todd asked her if she had been "overruled" by the other doctors in the department, and she said she didn't want to use that word, but that the other doctors were in a position to be much more objective than her.  They all felt it was a better option, to get the most bang for the buck, and help further research in the field, which made us feel like the other doctors just wanted to "guinea pig" Todd by enrolling him in the study.   This didn't sit well with us. The lack of confidence that she had in this decision troubled me.

She encouraged us to get a second opinion and that she would refer us to another physician at another research and BMT hospital.  In addition, they would still consider doing a second transplant at some point, if they could continue to "prove" that he can fight the disease, gaining more time between his last transplant and a future transplant: translation, that he can stay alive long enough and his condition improve enough to justify the second transplant.  Which, they feel is a good possibility if he could start taking the trail study drug: AG-221.  A good number of patients, most 60 years or older, who have not been candidates for a bone marrow transplant have sustained complete or partial responses to the drug since they have been on it.  More about this later.

As to pursuing the study, we would have to wait for the rest of the bone marrow results to come back, which includes cytogenics and the test confirming that Todd still has the gene mutation, IDH2 which is required to be enrolled in the drug study.  After suggesting this study to his doctor a while back, she investigated and found that Todd did have this gene mutation prior to transplant, when he was enrolled in a study with his oncologist at Cleveland Clinic after his diagnosis.  So, the study hospital  needs an official confirmation of this before Todd could be enrolled.  We all agreed that it would do us no good to pursue a second opinion or seek to enroll until we got these results back, which would take another week. 

We also needed to consider where he would enroll in the trial.  The Cleveland Clinic has applied to participate in the study, but it has not yet been approved.  Of course, there a multi-step process that the hospital must go through to obtain this approval.  She said it could take a month, or even longer to get this approval.  In light of this, she suggested that Todd could do another round of Vidaza, to keep his blast counts down, and then revisit the status afterwards.  The only problem with this, they still may not have the approval by then, which would put us in the same situation we are in now.  The closest hospitals that are enrolling patients are in Chicago and Nashville (Vanderbilt), both about six hours away.  We would not be required to stay during the entire trial, but we would have to return for tests at designated points in the study. 

Cleveland would obviously be closer at 3-4 hours away, but I hate to think about delaying treatment for another month or more with Todd's low counts, low energy levels, susceptibility to infections, and requiring blood transfusions every week. 

Concluding the conversation, this was the plan:
1.  Wait until next week, when all the test results were in, including the genetic test confirming the IDH2 gene mutation.  Without this confirmation, Todd would not be eligible for the study at all.  Then would have to go for the second transplant.
2.  If the results show he still has the IDH2 mutation, we will be seeking a second opinion at Vanderbilt Hospital in Nashville.  The BMT doctor will refer us to a doctor there.  We decided if we were going to get a second opinion, that we might as well have it done at a place where they are currently conducting the trial drug study, so that we could get feedback about how well it has been working.  If I had the money to fly often, I would rather go to Memorial Sloan Kettering in New York where the lead doctor and investigator, Dr. Eytan Stein is at.  He has been working with the drug the most.

So, with all this thrown at us in a matter of minutes, we were overwhelmed, sad, and heart broken.

We kept discussing the conversation that evening, questioning their recommendation.  We refuse to allow Todd to be a guinea pig.  I got up the next morning and decided that WE were going to make the final decision about what treatment he would do.  If we wanted to go for the second transplant, we would tell them that was our choice, and if they refused to do it, then we would go somewhere else.  

Still feeling like I needed more information about this decision, I began a further investigation into the drug and the trial study.  I'm so glad I did. 

About the Drug
The drug AG-221, is a pill that is taken over the course of 28 days per cycle.  Tests to check progress would include bone marrow biopsies, blood work, liver tests, etc.  After talking to the doctor that night, I was under the impression that the drug would work similarly to Vidaza, in regards to still producing low blood counts, but after further research, I don't believe that this is the case. 

After going on various websites, I found where Dr. Stein had presented his findings at the most recent ASH convention in December, 2014 on the drug company's website (Agios).  When I heard him say that patients taking the drug were responding in as little as one cycle, and that their blood counts had come up while blast counts had been reduced, I jumped for joy.  He cites one case where a patient's blast counts had gone done from 44% to 12%; Hemoglobin increased from 10.9 to 11.2; Platelets increased from 29,000 to 106,000; and ANCs went from .1 to 1.3!  (Stein, 2014, slide 28).  He even goes on to explain that even partial responses had to have platelets over 100,000 for it to be considered a partial response. This is so much better than what Todd is living with now (Platelets running 10,000-25,000)!    Here is the link if you are interested in this brief presentation.  Start at slide 18 and end at slide 29.  It does take a Shockware plug-in I believe to watch, but it shouldn't be an issue for most.
http://edge.media-server.com/m/p/s4b9a35f/lan/en

Key information: 

• Patients even on the lowest doses have received some response. Many have had relapse of their disease after a bone marrow transplant. 
• This Phase of the trial is to help determine the amount of the drug patients can take with minimal toxicity and still receive a response.  So, Todd would receive increased doses over time to "help determine the MTD or maximum tolerated dose and/or the recommended Phase II dose."  (U.S. National Institutes of Health. Purpose. 2015)  Retrieved from: 
  https://www.clinicaltrials.gov/ct2/show/NCT01915498?term=AG221&rank=3
• We are guaranteed certain rights, like they have to tell us which amount he will be given, he can stop or quit the study at anytime, and if they prove that a certain amount is the most beneficial, they can stop the trial and give him the appropriate amount.  (Memorial Sloan Cancer Center, 2015)  Retrieved from: http://www.mskcc.org/print/cancer-care/clinical-trials/how-decide-whether-clinical-trial-right-you  They have yet to reach a maximum tolerated dose yet. 
• The drug company runs the study at the designated hospital, under the care of a primary investigator (doctor) and co-investigators (other doctors), which can be a bit scary, but on the positive side, all of the costs of the drug, tests, and hospital expenses are paid by the drug company.   
• The job of the drug is to block the enzyme that allows the cells to mutate.  Therefore, it allows a good number of the blood cells to mature to healthy functioning cells. Thus, higher blood counts and lower blast counts.  Here is another great article that features information from Dr Stein.  http://www.targetedonc.com/conference/ash-2014/ag-221-sparks-durable-remissions-in-idh2-mutated-aml/2

 Of course, with any study, there are bad results too.  There have been some that have died from disease progression, or other causes and some that have not had any response.  But, a majority have done well.  With every treatment comes risks, but also the hope of remission.

In conclusion:

At this point, the only other step to the above discussed treatment plan, would be another addition:

3.  If the second opinion is the same, to pursue the trial drug study, then I think we will likely enroll soon thereafter at Vanderbilt, instead of waiting for the Cleveland Clinic to get approved.

Of course, all this is subject to change, in light of further information.

Thanks for your patience in waiting for me to get this posted and for the length of the post.  I will give another update when we have further information.  In the meantime, I expect that Todd will need another transfusion before Wednesday of this week.

We covet your prayers and support,
Kimberley

Other information about AG-221:
On YouTube:
https://www.youtube.com/watch?v=Pnkr2gZfr64

http://ashclinicalnews.org/trial-roundup-december-2014/

http://www.agios.com/pipeline-idh.php

http://investor.agios.com/phoenix.zhtml?c=251862&p=irol-newsArticle&ID=1916041&highlight=