MORE TRANSFUSIONS MAY BE NEEDED AS COUNTS REMAIN LOW

My last post left off with Todd going into the local oncologist/lab to get his routine labs done for his trial drug AG221 Day 15, Cycle 17 on July 27, 2016. We were anxious to see if the transfusion he received the following Thursday had helped to boost his blood counts.

Unfortunately, they did not. The results showed his Hemoglobin at 8.3, whites 

at 1.4, ANCs at 1.1, and platelets at 46,000.  This means he is once again close to needing another transfusion (hemoglobin < 8.0). This is also the lowest his immune system (reflected by the white and ANC counts) has been since he was in the hospital last October 2015. What does all of this mean for everyday living?  Taking extra precautions with activities like shaving with a razor (low platelets), living with severe fatigue, watching for a fever, and being cautious with what he eats (washing fruits and vegetables well, avoiding raw or under-cooked fish or meats, etc).  But worst of all, being severely anemic means  transfusions. The transfusions themselves aren't necessarily bad for him, even though they can result in a build up of iron, but they are inconvenient and often a multi-day process. First, getting labs to see if he needs a transfusion, then getting typed and screened, then setting up the transfusion at the hospital, and then the almost day-long process of getting the 2 units of blood. The depressing cycle  of fatigue and knowing your counts are dropping and hoping the transfusion will provide the much needed energy can be draining. 

I talked to Todd's bone marrow transplant Doctor this morning to get an idea of the game plan and where we go from here. She informed me that they ran a complete viral panel with his blood work and everything came back negative. If he had something bacterial he would have a fever. And the last bone marrow biopsy showed no increase in blast cells. 

This was her opinion:  Schedule appointment with Pulmonary Specialist to look at lungs, since he is still struggling with the cough. Next, deal with the anemia with transfusions until we know what's going on. I agreed with her that it may take some time to see if his complications and anemia is the result of "the disease evolving." While the AG221 is helping to keep blast counts low, it may not be keeping the disease from causing the anemia and low blood counts. My daughter Abby had brought up a good suggestion, which I put to her: "Would it help/be an option to increase the dose of his AG221?"  It was something she hadn't considered, but said it could be an option, but, if he is already suffering from the side effects of nausea, diarrhea, and high liver enzymes, that increasing the dose would likely make all of these side effects worse.  Not to mention, she would have to approach the drug company and ask it was even an option.

She had just received his cyto-genetics report back from the most recent bone marrow biopsy, and while there was no real major changes or new chromosomal abnormalities, she had noticed an increase in the number of 5q abnormalities, which could be a reason for the lower counts.  She said that about 15/20 chromosomes observed had 5q deletions. She said she may consider the idea of switching Todd's medication from AG221 to a medication used to treat MDS patients with the 5q deletion called Revlimid.  Since the transplant failure, we knew he had this option in our back pocket if we needed it.  It might be time to pull it out and use it.  Unfortunately, it is very unlikely that he could continue on the AG221 and just in the Revlimid, because it would be against the conditions of the trial study.  But, if Todd would become transfusion dependent, and the AG221 was deemed no  longer effective, then this is another good option for him.  We all have been so bullish on AG221 because it has worked so well for him, so we aren't going to let it go until we know for sure that it is not helping him.  I've even considered calling Dr. Eytan Stein at Memorial Sloan-Kettering in New York again if we can't get some answers, to see what he thinks.  Whatever it takes; that is what we will do!

I'm trying to make him rest and take it easy.  It has been so blistering hot in Dayton the past week, that being outside is more  difficult for him. I'm  getting good with the Zero-Turn Lawnmower!  We are planning on taking it easy this weekend, plus, Hannah Lewis is getting wisdom teeth taken out on Saturday!  So, I'll be nurse Kimberley to the invalids this weekend! (just joking). 

Todd will go get his blood counts checked at the beginning of next week, if he thinks he needs a transfusion.  I have to say I was impressed with his nurses at Soin Medical Center.  They sent him a personally signed card wishing him to get better!

The next trial appointment at the Cleveland Clinic will be August 10, 2016.  They have a full day of tests already scheduled.  Maybe we will find out something more by then.  We wanted to try to take a family vacation before the kids go back to college and school, but its not looking good since we just don't know how he is going to feel and if will continue to need transfusions.

Thanks for your support.

MORE INFORMATION:
About revlimid: https://www.drugs.com/revlimid.html

Day +97: Cleveland Clinic Appointment Results December 22, 2014

Todd's treatment appointment started with the routine vitals and blood work.  His counts were down a bit more today, but this was expected after the week of chemotherapy.  His whites were at 1.54 (1,540); Hemoglobin 9.4; and Platelets down to 20,000.  These counts were strong enough to alleviate the need for any transfusions.

We ran into a friend and former transplant patient and her husband in the doctor's waiting area.  Today was her last appointment!  Her chimerism was struggling a bit, but her counts were much higher than Todd's.  Her bone marrow biopsy came back clean; no signs of disease!  This was such a praise!  I told her how hard to was to see other patients from the transplant floor reaching their 100 day mark and getting to end transplant follow-up treatments, when we are back to where Todd started before chemotherapy and the transplant.  She empathized and told me that although it may seem that the marker to ending treatment seems to keep getting pushed backed for us, we just need to concentrate on getting to the same end result: recovery and remission.  It might just take Todd longer to get there.  I found such wisdom in this!  We don't understand why God is taking Todd down a different path, but I'm sure he has a reason (His ways are higher than ours).

We saw a different doctor today, an associate of his regular BMT doctor, since she is on vacation.  Todd's nurse coordinator also joined us to give us the latest news from his doctor.  He examined Todd as usual looking for any sign of Graft versus Host Disease rash.  I asked if there is still a good chance that he can get GvHD and he said absolutely yes; with the mixed chimerism, there is still a chance.  This would be ideal!  If Todd's body could develop a bit of Graft versus Host Disease it would help attack and kill his diseased bone marrow and give his brother's donated marrow the upper hand.

They took him off his magnesium tablets, which is normal a few weeks after stopping the Tacrolimus.  The Tacrolimus causes low magnesium, therefore the added supplements.  So, without taking the Tacrolimus for several weeks, he shouldn't need it anymore.  He does still need to continue with the rest of his medication until further notice.

Todd's cytogenetic report was back from his bone marrow biopsy.  It did show one chromosomal abnormality: a deletion in chromosome 5 [46,xy,del(5)(q13)(17), xy(3)].  He had this same deletion, along with three others earlier in the year in April and May, but they had gone away with the four rounds of Vidaza before his bone marrow transplant.  So, this one deletion has come back.

I asked what the next step was going to be, and his nurse coordinator jumped in and said that his doctor would like to get a couple rounds of Vidaza in before doing the second stem cell transplant.  So, we know that he will start his next round January 12, 2015.  I'm not sure if there will be a third treatment in February or if they will go on to the stem cell transplant.  They will be looking for a decrease in his blast counts when they do a follow-up bone marrow biopsy.

I also asked if there was a mistake in his chemotherapy, the trial medications, or the immunosuppression regimen during and after the transplant that allowed him to relapse.  I explained that I had heard of other patients having their own marrow suppressed instead of the donor and that his doctor was going to do this for the next stem cell transplant, and he said that this was not standard protocol for an initial BMT. He reassured me that it is standard procedure to always suppress the donor marrow because without immunosuppression  there would most definitely be severe GvHD.  I also asked if having the chromosomal deletions prior to the transplant contributed to the relapse of his MDS, and he said there is no way to know the answer to that question.  He explained that Todd's current doctor is trying to learn the answers to this question with her clinical trial.  In his opinion, nothing done during the first transplant contributed to the relapse.

We don't need to go back to Cleveland for treatment on Friday, December 26, as long as we arrange to have his CBC blood work drawn here in Dayton, and follow-up with any needed transfusions at a local hospital.  Our next Clinic appointments will be for treatment and seeing his regular physician on Wednesday, December 31, 2014, where we will discuss his latest chimerism results, the plans for future treatment, and to schedule additional appointments. 

His 100th day is Christmas Day.  Although we won't be celebrating a cure or remission, we will be celebrating life! 

Bone Marrow Biopsy Results returned prior to transplant.

Todd's bone marrow transplant doctor sent him a message yesterday, August 22, with his cytogenic results from the bone marrow biopsy he had on August 7, 2014, as part of his staging leading up to the transplant. 

We were shocked to learn that with four rounds of Vidaza, all four of the chromosomal abnormalities/deletions he had been diagnosed with biopsy earlier this year, had been reversed, and that NO deletions were detected on this biopsy.  While we knew this was possible, we were surprised to learn he had responded so well to the chemo.  According to the transplant doctor, this is great news to receive prior to having the bone marrow transplant. 

Not only did the Vidaza help with the deletions, but his blast counts were still down to about 1%.  These results will give Todd ideal conditions going into the transplant.  We are thrilled, but couldn't help to question, "Why should we still do the transplant then?" 

So, I began trying to pull up research on the reversal of chromosomal abnormalities after receiving Azacytidine or Vidaza.  After reviewing some research, I learned that these results are short lived and are dependent upon repetitive use of the drug.  It seems like with those who did achieve some kind of remission, it was only for four to fifteen months before relapse.  Some also suffered from neutropenia, which is low blood counts that require treatment, and others had some long-term side effects from the toxicity of the drug. (Raj and Mufti, 2006: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936359/#!po=46.9780)    The actual dysplasia of the blood cells that is found with the initial MDS diagnosis are still present in all cases, meaning there is no change with cause of the disease. 

Once again, we feel reassured that Vidaza was a great short-term option for pre-loading before the transplant, but it is not a great long-term solution for Todd's case of MDS.  We still feel like the transplant with his perfect match donor is the best long-term solution for him at his age of 45 and with the progression of his MDS.