Bilirubin numbers too high; No AG221 right now

Todd didn't get to go to his routine trial drug appointment last Wednesday, February 10, 2016. He was up the night before with abdominal pain. He thought it was indigestion or something he ate. It finally passed after several hours but we didn't get much sleep. 

On Friday, he asked if his eyes and skin looked more yellow or jaundiced than normal and I said yes!  I had been asking him to contact his doctor at Cleveland Clinic to check in and get his biopsy results. He decided not to take his trial drug AG221 that day, because we know that it elevates his bilirubin at least 2-3x higher than normal, even though this increase is within the acceptable limits of the drug trial protocol which allows his bilirubin levels to go up to a maximum of 5x the normal level. 

Normal bilirubin about 1.5

Maximum bilirubin allowed on the trial 7.5. But even then they don't like it that high, because it can cause liver injury. 

Todds level on the drug usually stays around 2.5-3.5. 

I decided that it we should call the doctor. Not only I had noticed that he looked more yellow, but had asked him if his urine looked like it was darker than normal. Almost brownish red. He said he didn't think so, but after putting the stomach ache, dark urine, and greater yellowing/jaundice, I thought we wedded to ask. 

I called his doctor, but she was out of town at an ASH conference, but his nurse said she would run it by his trial nurse Sam and the doctor taking over for his doctor. Sam called me back quickly, and it was decided that they need some blood work. She worked with the doctor and faxed in orders to our local lab and have it processed STAT. 

Within 3 hours he had the blood work drawn, the results back, and we got a call back from Sam. All of our concerns were justified. His Total Bilirubin was 7.7 and his direct bilirubin was 4.4. His Alk phos was off the chart at 400!  (Normal  45-115).

So, Todd was told to go off his trial drug immediately. They scheduled an appointment for him at Cleveland Clinic on Tuesday where they will do some extensive blood work and see the doctor. 

Sam also looked up Todd's last bone marrow biopsy results, which sowed another 1% increase in blast cells, bringing them up to 4%. I still don't think this alarming, but I don't like that in the last 4-5 months his blasts have gone up slightly each time. 

 

Please pray that they will find out why his bilirubin went up so much and can recommend appropriate action. I think it is just the accumulation of the trial drug over time causing the escalation. Especially since he already suffered some liver injury when he was in the hospital last October where he suffered similar elevated numbers due to the addition of numerous medications to get his fever down and treat the pneumonia. The highest his bilirubin was then was 8.7 which was crazy high. Even then though his alk phos numbers were about 219. 

I'll post an update of what we learn after Tuesday's appointment. Thanks for your love, prayers, and support. 

January 2016 Begins Month 11 of Trial Drug AG221

It is hard to believe that as of this Wednesday, Todd will begin his 11th month on trial drug AG221. I was reading a news update on the drug (link here:  http://www.nasdaq.com/press-release/agios-announces-data-from-ongoing-phase-12-trial-of-ag221-showing-durable-responses-in-patients-20151206-00039 ).  It looks like they are continuing with additional trials this year for MDS patients in addition to AML patients.  It looks like Todd is not the only one seeing some improvement. When you read the article Todd is one of the MDS patients having a response to the drug. 

As we read the article, we were able to reflect on where he was a year ago! He was so weak and transfusion dependent. I was frustrated with the current rounds of chemotherapy (Vidaza). It is amazing that we know so much more about AG221 now than we did last year!  

I'm so grateful to Dr Etyan Stein for his work on getting this trial information in the news and Agios for putting his presentation online where I was able to watch it and encourage Todd to go on it and fly to New York to see Dr. Stein at Sloan-Memorial Hospital in New York City. 

Todd's last appointment in December went well. His blood counts and his MDS are holding steady. For those of you who are interested in CBC counts for comparison: White: 4.02; Hemoglobin: 10.9; ANCS: 3.42; and Platelets: 51,000.  His Bilirubin remains higher than normal, but still within the study limits. We did get his last bone marrow biopsy results back and they showed a 1% increase, resulting in a 3% total blast count. We aren't upset about this because this is essentially not enough of an increase to make a difference. They always have to allow for a small percentage of error or for slight variations as counts and bone marrow samples differ. The good news was that his cytogenetic report from that biopsy did not show any additional chromosomal abnormalities. 

Early in December, I did have a candid conversation with his Bone Marrow Transplant Doctor about the new research about the TP53 genetic mutation.  This mutation is acquired and is usually what causes the cancer or disease.  There has been some studies trying to determine whether patients with this TP53 mutation, don't respond well to transplants or are more resistant to therapy.  She discussed how the TET2 mutation also is being studied in relation to patients who end up with a "poor prognosis" or at higher risk.  I had learned about the TP53 mutation after reading a friend's blog about her son with Leukemia, who had relapsed after a bone marrow transplant, who is now relying on an alternative trial treatment that using T-cells.  (Craun, November 2015). And, when reading the last issue of the MDS newsletter, there was an article about TP53 and its connection to a patient's prognosis who has this mutation. (MDS News, Fall 2015). I asked Todd's doctor if Todd had this mutation, and she knew the answer immediately: Yes, he did.  If this research proves true, it would answer the nagging question of why Todd's bone marrow transplant failed.  It would also be helpful in the decision to have a second transplant someday; if the evidence shows this mutation inhibits a successful transplant, we would likely eliminate that option in the future.

I'm so thankful that he has not suffered any of the severe adverse events or reactions to the drug. Even though he has suffered terrible nausea and high liver function counts, it has been tolerable. 

I'm a bit disappointed that he has to have another bone marrow biopsy AGAIN this visit. The other tests are less invasive and they don't bother him as much. Hopefully, after he has been on the trial drug for 12 months, they will lessen the frequency of biopsies, although I have no assurance of this.  We were assured though that at after 12 months, his trial study appointments at the Cleveland Clinic would change in frequency from every two weeks to only once a month!  This will be great!

We said goodbye to Ashley, his primary trial nurse, who is leaving the program to take a nursing job back on the Leukemia floor.  We will miss her, as she was there for us from the beginning and whenever we needed answers.  We are confident that we will be in good hands with her replacement, Sam, who has been on the trial study team from the beginning too. 

So, Todd will have a full run of tests this Wednesday, as he plugs along on AG221.  We are curious to see how our new insurance, through the Affordable Care Act, works for us this year. The main focus now is to get him through Winter without getting sick.  We haven't done much socially, and fear vacation travel at this point, but it would be nice to get away for a little bit over spring break. 

 A few concerns and prayer requests:

First, like I stated in the last post in December, we received paperwork from the Social Security Disability Board asking for detailed information in their review of his continued approval for benefits, which is beyond comprehension to me!  I filled out about 10 pages of appointments, treatments, hospitalizations, transfusions, medications, etc. only to receive a second request form (8 pages) last week asking us to describe his daily functions in detail!  I can't imagine how anyone could look at these papers and not determine his continued need.  His health is so precarious, dependent on stable blood counts and staying completely healthy.  We learned how quickly he health could change in October 2015 when he was hospitalized for a cold and pneumonia for 13 days!  As this is our only source of income right now, we are desperate that it continues.  I don't understand how he was a productive citizen and paid the maximum into the system for years, and then we he needs it, they have to challenge it! 

Second, speaking of income, I still haven't found a full time job.  I graduated with my MLIS in December 2015, only to be let down by what little value these credentials are in obtaining a position.  I apply weekly for jobs, and try to do something productive everyday in the job search.  I have several applications pending at UD right now, but everything else I have applied for has not produced any offers.  I am also actively seeking volunteer experience and trying to schedule to attend several professional organizational meetings, but these have also been in limbo.  If you know of anyone who is hiring, even outside the field, please let me know!  I have applied for positions outside of field, and one of those applications is still pending.  It is not always what you know but rather who you know that helps land that job!

We took the house off the market for the holidays, as we needed a break from showing it and our listing had been on the market too long for serious offers.  We will likely put it back on the market in early March. 

We appreciate all those who have sent Christmas cards, money, and gift cards, especially Beau Townsend Ford's Employee Christmas Club Fund and that of our friends and neighbors. 

Right now, we are just trying to appreciate Todd's stability and giving God the praise for the blessings we have daily! 


References:

Craun, Gina. November 24, 2015). Windshield Wipers. Cainan Craun. Caring Bridge. Blog.  Retrieved from: http://www.caringbridge.org/visit/cainancraun/journal/view/id/56549676a589b45a417219e8

Prognostic Impact of TP53 Mutations. MDS News, Fall 2015,Vol. 21, Issue 2. page 11.  Retrieved from: http://mds-foundation.org/wp-content/uploads/manual/2015fallnewsletter.pdf

End of another year: We are blessed!

Well, it's been a long time since I've posted, but I'm finished with graduate school finally! 

Todd is doing so well!  I had to fill out papers for his Social Security Disability Review and write down all the dates, places, tests, biopsies, ER visits, hospitalizations, etc.  It hit me anew: What a rough year this has been!  

While recalling these struggles, I couldn't help but cry, but I'm so thankful he is alive and having a good quality of life. Things looked so bleak January through April.  He had so many CBCs and transfusions during those months. He was so weak and tired. I was so tired. Our financial resources so thin. How did we get through it: Faith, Hope, and Love. 

I can't begin to thank so many of you for your prayers, help, donations, gift cards, food, gas cards, and those faithful friends  who called and visited us whenever possible, like Pastor Chuck Moore from Hillside Chapel. Such a faithful servant of Christ. And friends like Darsie, Dana, Pam, Vicki, Donna, Chris and Lynda, and my parents and family, who went beyond kind words and stepped in with their time and hard work.  Oh, and we have 3 amazing Kids who have been loving and supportive even though these hard times have shook up their world. Love you Abby, Lewis, and Ellie!

I noticed on my "Time Hop" app yesterday, that I was thanking whomever was sending us gas cards anonymously, and I'll be blessed, they still are sending them a year later!  We just received one this week!! How blessed are we! And how much love and faithfulness do these servants of Christ have?  

A friend sent me an IM today offering  me encouragement. She encouraged me not to loose my faith, that God has a plan. I have to admit I have had more doubts than ever before in my lifetime, but the faith and encouragement of others, that I know God has been able to use, had sustained me. 

We have seen so many ups and downs, shared in the struggles of our friends  in their own fight against cancer, even loosing our friend Rick to cancer on Todd's birthday on May 9, 2015. Knowing others have suffered relapses and set backs too, like Jim and Jeff. Sometimes you wonder if it is just a matter of time, but then we have times where we can rejoice with those friends like Ron and Nancy, who have had successful transplants and remain disease-free!  

I was fearful after Todd's hospitalization in  October with the cold and pneumonia, not to become to complacent in our fight. Yet, once more I feel optimistic that he has come this far and we will continue to fight and live our lives to the max. 

At this Christmas Season, I'm so happy to say we are blessed and continue to look forward to a healthy new year with our family. We are anxious to spend some special time together with our children and family. 

Merry Christmas and may God bless your new year! 

Fall 2015 MDS Newsletter

Just wanted to share with my fellow MDS patients and caregivers the link to the latest MDS Newsletter. 
http://mds-foundation.org/wp-content/uploads/manual/2015fallnewsletter.pdf
The American Society of Hematology (ASH) convention begins around December 5, 2015.  When they post some of the speeches and news, I'll follow-up with a report here.  I'm anxious to hear the results of the AG221 trial drug study update.

Thanks!

Post-Discharge Concerns with Liver Function

Todd was discharged from Cleveland Clinic on Monday, October 26,2015, after a full 12 days in the hospital.  It too was a long day.  They started with the doctors making their rounds.  His counts looked good, and he was not febrile, so they decided to start him on the new oral anti-fungal drug, Posaconazole that morning.  His total bilirubin looked a bit high, but under the 7.5 allowance per the trial study guidelines, so they also allowed him to take his chemo trial drug AG-221, along with the oral Cipro antibiotic to replace the IV medication Zosyn.

His blood counts were Whites: .95; Hemogloblin 10.8; Platelets 41,000; and ANCs .66
Liver counts: Total Bilirubin 5,8; Alkaline Phosphatase: 353; ALT: 129; and AST: 84; PT INR 1.1  These numbers weren't great, but tolerable at this point. The doctors were hoping that the Posaconazole would allow these numbers to go a bit lower, but by this day, there were trending up.

It took forever to be discharged of course.  His nurse had to deaccess his port, and said she needed to use heparin, but I told her that his new Power Port, did not need heparin.  So, apparently, she had to take an extraordinary amount of time to look it up, because I had to go get her an hour later, and she said that I was right, his port didn't need flushed with heparin.

The other delay, was waiting for his perscriptions from the pharmacy.  The nurse had arranged for bedside delivery and someone did come by early in the afternoon telling us that the co-pay for the Posaconazole was going to be $70 and was that ok.  We said yes, we didn't have a choice.  She went off and didn't hear from anyone the rest of the day. After our nurse tried to call there, I decided I was going to pick them up myself so we could get out of there.  I went to the main pharmacy and they didn't have the prescription there, it was at the Crile Pharmacy across the skyway.  So, I had to walk over there.  Luckily, a very nice lady in transportation was there with the golf cart and she offered to drive me over (yes, it is a long walk).  When I got there, I realized that the prescription was only for 10 days, not 30 days!  So, $70 for only a 10 day supply.  The pharmacy had the scripts there and had no intention of getting them over to us, as far as I could tell.

When I got back, the nurse was ready to go over his discharge instructions and ordered a wheelchair to take him to the entrance for me to pick him up.  By this time it was about 4:30 p.m.  Needless to say, we hit Cleveland rush hour traffic and didn't make it home until about 8:30 p.m.

On Tuesday, October 27, Todd had a follow-up appointment with his local oncologist, at his request, so that we could "reconnect" even though all Todd really needed was blood work.  It was a waste of time, the local oncologist still can't remember the name of the trial drug Todd is on, and asked us why were we there!  Ugh...

Blood counts on Tuesday were mixed: Whites .7; Hemoglobin 11.3 (Never been this high since before transplant.  Lack of fluids can make his blood concentration higher though).  Platelets: 89,000.
We didn't get his CMP (Complete Metabolic panel) and had to request the results, but they said they wouldn't be able to get them and call us back until the following day, Wednesday.  Ugh...

We went home and took a long nap, as we both were wiped out and happy to be sleeping in our bed.

Wednesday and Thursday, October 28 and 29, 2015, Todd was tired.  I mean sleepy and not getting out of bed tired.  I didn't understand this.  His hemoglobin was so high!  Then why was he so tired?  I just chalked it up to fatigue.  I was dragging, and I'm not sick!

I didn't hear from the local oncologist's office with the liver results, so I had to call and ask for the results via a voicemail.  When I got home from doing my practicum at UD that afternoon, they had Still, something seemed "off."  I texted his trial nurse with the results later:
Direct bilirubin was 6.4; Alkaline Phosphatase: 448;  ALT 200; AST 107;  So, these numbers were still going in the wrong direction and she asked if he was having any abdominal pain.

Until Friday, he had taken his AG221 and his Posaconazole every day along with his other medications, after getting the advice from his BMT doctor on Thursday.  By Thursday night, he was having stomach pain about an hour after he ate.  He was up pacing the floors, feeling like he did that night in the hospital when he was throwing up.  His stomach finally settled down, but I was going to ask the doctors if they thought it might be a gall bladder attack.

Friday morning, we had to leave the house by 5:30 a.m. to get to his first appointment at the Cleveland Clinic by 9:00 a.m.  First up, was the infectious disease doctors.  After a thorough exam, they said they wanted to see his blood results for the day and then confer with his BMT doctor.  In the meantime, they set up an appointment for a follow-up CT scan on November 18, 2015 to see if the pneumonia was gone or not.  I asked about the stomach pain, and they said didn't think it was anything in his abdomen, especially not the gall bladder.

After that, we headed to treatment in the Taussig Cancer Center, were they drew his blood.  one of the lab's machine was  broken, so it took over 2 hours just to get the CBC results:
Whites were up a bit at .99; Hemoglobin had dropped to 9.5; and platelets had dropped to 50,000.  ANCs and liver results were still not back by 2:00 p.m. when we headed upstairs to see his BMT doctor.

When we got upstairs, his trial nurse was there and his BMT doctor announced that they wanted to him discontinue taking BOTH his AG-221 trial drug, and the POSACONAZOLE.  I was shocked!  The liver numbers must have been bad.  They finally had the results back:
Total bilirubin was 5.6, but the Alkaline Phosphatase was 558!  AST 441! and the ALT 573!

While I didn't realize at the time how bad these numbers were, I would later find out that they were off the chart and severely dangerous!  My first concern was fighting the pneumonia with NO anti-fungal drug.  I asked the doctor: can't the fungal infection get worse?  Her first response was that "they" or she still wasn't 100% convinced that it was a fungal pneumonia, but that she COULD be WRONG.  (Shocked again).  I brought up the most recent CT scans that showed nodules, which could be indicative of a fungal pneumonia, but again she said it isn't conclusive, but she could be wrong.  This raised a red flag to me.  So, what if it was fungal and they weren't going to treat it?  He would start showing symptoms again?  Yes, I could see this is what she meant; I had my answer.  If he started running a fever again, or having lung problems, then it could be proof that it was fungal.  Hadn't this already happened once while he was in the hospital?  They took him off the anti-fungals, and that night he spiked a fever. 

Then, we asked at what point could he start taking the AG221 again?  What was the criteria they were going to use?  They said at this point, his liver enzymes would all have to return to "baseline" numbers.  I asked what, 1.5?  And, the trial nurse, said no, the drug company wanted those numbers back to the levels they were before he started taking the drug!  (Another shock). Going through my mind? Without the trial drug, it would only be a matter of time before his blood counts would decline, making him neutropenic and possibly needing transfusions again!  After I brought this fear up to the doctor, she said she didn't think his numbers would decline that fast, but in my mind I remember that the first week he took the drug, it reversed his situation.  Would a reversal of not taking his trial drug, make them decrease in a week?

This was not the news we had anticipated at all!  It was determined that it would do no good to continue to check his counts via blood work in Dayton, since there really wouldn't be much they could do.  Obviously, if he becomes symptomatic, can't get out bed, weak, bleeding, or other signs of low blood counts, I could run him into the Cancer Center/Local oncologist's office for blood work.  I asked if the Cipro could cause any more elevation of his liver enzyme counts and the doctor said no.

Bottom line:  Liver enzymes too high; no trial drug and no anti-fungal medications.  Return for regular trial day, next Wednesday, November 4, 2015.  He was already scheduled to go in for that day, since it would be Cycle 8, day 1, his last 10-hour day of blood draws on the trial.  So, this protocol may not take place if it is determined when he gets his CBC pre-testing that his liver enzymes are still too high and he still won't be allowed to take the drug that day.  If the numbers have come back down to baseline numbers, then they will proceed with giving him his dose of AG-221 that day, and then commence the 10 hour day of testing.

We didn't get home until about 8:30 p.m.  It had been a 15 hour day of traveling and appointments.  I drove both ways, up and back, so Todd could rest.  Even though I was tired, something still seemed "off" to me about the appointments.  The trial nurse was extremely quiet, and Todd didn't like me bringing up the symptoms of being sleepy, tired, and having the bad stomach ache the night before, but I felt there had to be some reason for this.  So, I began searching for symptoms of elevated liver functions, and bam! There is was on several websites:

Symptoms of liver damage
Jaundice; severe fatigue; fever, abdominal pain; severe nausea and vomiting; bleeding that does not stop after a few minutes; and unusual swelling in feet or legs or weight gain of greater than 3 to 5 pounds in 1 week. This from http://cancer.unm.edu/cancer/cancer-info/cancer-treatment/side-effects-of-cancer-treatment/less-common-side-effects/organ-problems/liver-damage-hepatotoxicity/

From the National Library of Medicine: Severity Grading In Drug Induced Liver Injury (DILI):
Symptoms: fatigue, weakness, nausea, right upper quadrant pain, itching, skin rash, jaundice, anorexia, or weight loss.  (paragraph 9).

Looking at these symptoms, it was clear, that Todd had many of them!  Why didn't any of the doctors he saw tell us this! NO ONE said, yes, these are symptoms of liver damage!  I have a feeling, no one wanted to tell us!  It is hard to believe they didn't know, but I guess, I could be wrong.

The more I read, the angrier and more worried I became.  It was looking like these liver enzyme numbers were indicators of some level of liver damage.

While the first chart on Severity Grading Chart is mainly for AIDS patients, the second half of the document and chart is for cancer patients on chemo drugs.  

I was also researching his liver metabolism gene mutation. Apparently, this has not helped with his liver coping with the medications. 

I'm just glad that they were mindful to watch out for high liver counts and now my apprehension of Todd going off the trial drug has dissipated. I know that keeping his liver from severe or permanent damage is more important right now. 

Day 12 Hospitalized: Feeling Better; Ready to come home

Day 12 Hospitalized: Cleveland Clinic, October 25, 2015

Today was the first day they were able to start the Posaconazole by tablet: 3 tablets.  They also took away the IV Antibiotic Zosyn after his morning dose and will begin the tablet antibiotic Cipro this evening.  They will continue to prescribe this antibiotic after he is released.

Surprisingly, his hemoglobin has been in the tens the last two days; they haven't been this high since pre-transplant I believe.  When I mentioned it to his trial nurse and she said that it is likely that he is a bit dehydrated, his blood no longer full of IV fluids.

About  5:00 p.m., I noticed his cheeks were starting to look red, like a fever was coming on.  So, I went to get his nurse and he wasn't febrile (having or showing the symptoms of a fever), but close at 99.5.  It hadn't got any higher by bedtime, so I think he will be alright.  He ate a bit better today, but of course, with the new antibiotics, he has developed some diarrhea with it.
CBC:  Whites: .69; Hemoglobin: 10.4; Platelets 46,000; ANCs .47
Liver Function:5.8 Total Bilirubin; Alkaline Phosphastase 353; ALT: 129; and AST 84

These numbers seem to be going up, but were in the allowable range for him to take his trial drug. They will want to see these tomorrow and hope that they don't go up. 

Day 11 Hospitalized: Stomach upset keeps Todd up

Day 11 Hospitalization: October 24, 2015
CBC: Whites: .57 Hemoglobin: 10.1 ; Platelets: 56,000 ; ANCs: .31
Liver Function: Total Bilirubin:3.8, Alkaline Phosphatase:322 AST:69 ALT: 85


Todd was feeling good.  Last night we stayed up late watching TV and eating/snacking.  We napped a lot through the day to catch up on much needed sleep.  Unfortunately, about 3:30 a.m. Todd woke up with a terrible stomach ache, and we were paging the nurse for something to settle it.  By 4:30 a.m. he was throwing up.  Nothing seemed to help: they tried IV Ativan, since it works like Phenegran.  He tried to take Oxycodone for the stomach pain, but that didn't help either.  The AG221 drug protocol prohibits antacids like tums, Malox, etc.  He felt bad until he was finally able to sleep by 8:00 a.m.  His trial nurse was on the floor and said he could have simethicone, for any gas in his stomach. 

The nurse practitioner, the infectious disease doctor, and Dr. Sekeres made their rounds later.  Based on the recommendation of the infectious disease doctor, they want to try a "better" type of anti-fungal drug that is stronger, but with less side effects, hopefully, called Posaconazole.  This can be taken by pill and would allow immediate release.  Dr. Sekeres would like him to be on it a day or two to see how it effects the bilirubin.  Unfortunately, they had already given him the Micafungin for the day and didn't want to double dose him.  So, tomorrow morning they will give him the Posaconazole and then check his numbers early Monday morning.  Either way, he should be able to go home (Please???); either with the home healthcare set up at home for the Micafungin or with a prescription of Posaconazole.

He ate very little and slept almost the entire day. I was restless and wishing I had someone to talk to something diverting (besides homework) to help pass the time.  The Cleveland Clinic, while like a bustling city during the week, is dead during the weekend with half of the limited restaurants here closed.  I ordered some hot Chinese take out that delivered to the hospital and watched the Ohio State Buckeyes whip up on Rutgers, until that wasn't even fun anymore!  I'm afraid that was the highlight of the day.