Nurse Visit part 2: Graft versus Host Disease (GvHD)

Graft versus Host Disease in a condition that can occur after an allogeneic transplant in which "the donated bone marrow view the recipient's body as foreign, and the donated marrow attack the body." (Cleveland Clinic Foundation, 2014).

It can be either Acute (aGvHD) or Chronic (cGvHD). Todd could get one, both, or experience neither. 

Since Todd is receiving his bone marrow donation from his brother, who is considered to be a "perfect" 8 of 8 point match donor, the risks of developing GvHD are somewhat lower. His young age also helps decrease this risk. 

If  acute GVHD occurs, it will usually show up when his brother's cells have "grafted" into Todd's body (within weeks).  Chronic GvHD can develop anytime, even years after the transplant. 

Acute GvHD usually develops in the skin, liver, eyes, or gastrointestinal tract.
Symptoms include:

Skin: rash or reddened skin

Liver: abnormal blood tests (liver) and/or yellow discoloration of the skin/eyes

Gastrointestinal: nausea, vomiting, diarrhea, or abdominal cramping. 

Eyes: increased dryness/irritation. 

Chronic GvHD can manifest itself in these same areas, but in additional places too including the mouth, lungs, neuromuscular system, and/or genitourinary tract (bladder/sexual organs).
Symptoms for these areas include: 

Mouth: dry mouth, white patches inside the mouth, pain or sensitivity to spicy foods. 

Lungs: Shortness of breath, changes in chest X-rays. 

Gastrointestinal: difficulty or pain in swallowing. 

Neuromuscular: fatigue, muscle weakness, or pain. 

Genitourinary: urinary frequency, burning or bleeding with urination, or penile dysfunction. 

Many of his medications can cause similar side effects making diagnosis difficult. Detailed tests and consultations with specialists will help distinguish the difference. Checking current results with baseline test results taken prior to the transplant can be helpful.

While GvHD can be deadly in some rare cases, most cases can be counter-acted with medications, though some can cause long-term side effects. Since Todd's brother is a perfect donor match, we are praying that the chances for developing GvHD are slim.

On the flip-side, GvHD does have some good benefits.  A slight case can be positive.  "The same immune response responsible for attacking your normal cells is also monitoring and destroying any surviving cancer cells."  (Cleveland Clinic Foundation, 2014). This is called the Graft versus Tumor Effect. In other words, Todd will have his brother's bone marrow in place of his own: normal, healthy bone marrow.  If any of Todd's original unhealthy bone marrow is still left, then Todd's new immune system from his brother will attack these old dysplastic or cancer cells.  Also, patients who develop GvHD have been shown to have lower disease relapse rates. 

So how can he avoid GvHD?  Using a perfect or best match donor's cells and giving him preventive immunosuppressant medicines after transplant.  Constant monitoring of symptoms is also imperative to diagnosing and controlling GvHD symptoms. 

A major time of developing or confronting GvHD is when the doctors take Todd off his immunosuppresant medications.  Some patients have to continue these medications for longer than the initial treatment time, sometimes for months, years, or indefinitely. 

I have done the best to describe GvHD as simple as possible.  I have used the information handout (Revised 2/27/2014) provided to us by The Cleveland Clinic Foundation in our transplant information binder.  Please follow this link to find this information online: http://my.clevelandclinic.org/services/Bone_Marrow_Transplantation/hic_Graft_vs_Host_Disease_An_Overview_in_Bone_Marrow_Transplant.aspx

Cancer Etiquette: How to talk to people with Cancer.

I just read an insightful article written by Rosanne Kalick, titled, "Cancer Etiquette: A Survivor's Perspective on Effective Communication" which was in the Caregiver's Guide for Bone Marrow/Stem Cell Transplant produced by the National Bone Marrow Transplant Link (2007). This article is a just a taste of her book, similarly titled, Cancer Etiquette: What to Say, What to Do When Someone you Know or Love Has Cancer.  (Available at Amazon: http://www.amazon.com/Cancer-Etiquette-What-When-Someone/dp/0874604508/ref=sr_1_1?s=books&ie=UTF8&qid=1409238495&sr=1-1&keywords=cancer+etiquette). 

There was so much great information in the article (link attached).  I learned some things that I will take to Cleveland with me and try to apply when I talk to Todd or ask him questions.  For example, instead of asking how he is, ask, "How are you today?"  (p. 16).  Another admonition: "don't tell the patient how great he looks" but instead say "You are looking stronger today."  She gives advice about statements that dismiss concerns, like "you're not going to die" and identifies sensitive topics to avoid discussing like: hair loss, personal issues (sexual side effects), and/or your own strong religious views unless these were topics you were able to discuss openly before the cancer diagnosis. (p.16-17).

The best advice she says she can give: "When in doubt about what to say, don't say it." The most important words to say instead are: "I love you."  (p.17).

In offering help, Kalick says to be specific about what help you can offer.  Instead of saying things like, "Let me know if I can help" or "If you need me, I'm here" say (for example), "I'm available on Monday evenings to run errands" or "Can I bring a meal on Friday?" (p. 17).

Kalick gives some advice about visiting I found useful. She says that your presence, touch, or hug is often more important that words or there may be times when "silence may be best the connector." (p. 17).

She wraps up the article by giving suggestions or guidelines for gifts.  Transplant patients are much different from other patients in regards to what they can eat, touch, or have in their room.  Magazine subscriptions, CDs or books that are "short and light," emails, video messages, photos, or jokes are good suggestions. (p.18). I have also read that soft blankets or hats/beanies are nice for any cancer patient.  She says to "plan for the long haul" and "work in community" when giving support to a family dealing with cancer. 

I have a general mailing address for Todd, but we won't know his room number until he is admitted.  I will post this information all at once when I get it on September 7, 2014 if anyone wishes to send a note of encouragement.  In the meantime, I am putting together a photo album to take with us.  If you would like to send me a funny or cheerful photo via email or snail mail, I would love to include it.

I wish I had read this article sooner.  It has helped me to re-evaluate my words and my actions when addressing cancer patients.  Hope you find a moment to read it!

Please follow this link to read the short three-page article: http://www.nbmtlink.org/resources_support/cg/cg_dontknow.htm 

A temperature leads to a visit to the Emergency Room

In Todd's fourth round of Vidaza, on day 2, August 12, 2014, he began to get chills and then spiked a fever of 101.5. Anytime a chemotherapy patient gets a fever over 100.4, you are advised to contact your physician because it can be a sign of infection. 

Todd had been having headaches with this round of Vidaza and was taking Tylenol about every 4-6 hours for relief.  He had been feeling flushed and hot mixed with chills.  He covered up with a blanket and then got ready for bed, taking another dose of Tylenol for the headache.  He still felt hot about midnight, when Abby was on her way to bed.  She went hug him and immediately felt heat from his body.  I grabbed the thermometer, and we took it several times to verify it before calling his local oncologist.  The doctor advised him to go to the emergency room to have it checked out. 

Todd was very reluctant to go, he was tired, and by this time the Tylenol was working to reduce his fever.  However, we were concerned that there still could be an infection and feared the Tylenol could have been masking the fever longer than just that evening.  The only thing that convinced him to go was that they could take blood work to verify an infection and that we didn't want to jeopardize the transplant process with an infection that could get out of hand if not treated. 

So, my daughter and I packed him up and took him to the emergency room at our local hospital.  They took blood cultures looking for infections, a chest x-ray, and a urinalysis.  Everything came back showing NO Infection, but his white blood counts were very low: 1%.

He was released after 4:30 a.m.  The flushing, headaches, and itching symptoms as a result of the Vidaza continued through his fifth day of treatment.  No 6th or 7th days of treatment was given in his fourth round due to the insurance cancellation. (See post).

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.

Treatment halted due to Insurance Cancellation!

Todd went in for his day 6 of Vidaza out-patient chemo today, August 18, 2014 but didn't get past the check-in counter. He has to present his insurance card everyday before treatment. Today he presented his card, but was told his insurance was inactive.  He called Anthem Blue Cross and Blue Shield while the receptionist was checking and they said his policy had been CANCELED, unknown to us, as of July 31, 2014!

Traumatically, Todd heard the worst news when he called his employer to find out his employer had allowed his insurance to be cancelled. Todd had been paying his insurance premiums out of his private short-term disability income since he left work to be placed on disability. We thought everything was fine and had just praised his employer for such great insurance coverage to our friends and Todd's co-worker during a lunch date. Apparently, after twelve weeks of not actively working, he needed to be placed on COBRA insurance.  We later learned that there had been a meeting between the insurance company and Todd's boss where this change was discussed, but NO ONE NOTIFIED US! I believe the law or rule states that we are supposed to receive a 2 week notice to sign-up for COBRA so we can pay the insurance premiums at the COBRA rate.  The local insurance agent told us that Todd's employer handles this human resource responsibility, but for some unknown reason they didn't do it.  We received no notice, no phone call, no letter, nothing!  No one can tell us why were weren't notified in advance so that we could make the payments and fill out the paperwork to continue our coverage seamlessly. 

Todd called his employer and tried to get this straightened out.  We were distraught.  How could they do something like this to an employee of over 20 years?  How could they do it knowing Todd is facing a major life and death medical procedure in less than three weeks that is likely to cost hundreds of thousands of dollars?  Our family is already under tremendous stress, without learning we lost our health insurance at the most crucial time in our life! 

Not only did Todd NOT receive his last two days of Vidaza treatment, but our oldest daughter had two doctors appointments scheduled these same days before she left for college on Wednesday, August 20.  Todd's brother was scheduled to go up to Cleveland to have all of his pre-transplant donor health tests done on Thursday, August 21, this same week.  Our daughter couldn't get any of her prescriptions before she left (and still hasn't got them) for college.  Nothing could be approved.

We had to scramble on Monday to write a letter, fill out a new application for COBRA insurance and mail checks for July and September insurance premiums to Colorado by priority mail so we could get it re-instated.  They wouldn't reinstate it until they received the checks!  I have to thank the insurance agent for working so hard to get us reinstated as quickly as possible. She really cared and tried hard to fix the situation.  On Wednesday, while driving to move-in our daughter into our dorm, the agent emailed us a new Anthem application that had to be completed and re-sent the same day, so they could temporarily approve Todd's brother's appointment at The Cleveland Clinic for Thursday.  So, half way through my daughter's move-in, we  had to stop, go to the University library where we could open my email,  download and print the application, fill it out, and then find someone to help us scan the signed application and email it back to the agent so she could forward it to Anthem.  This was extremely stressful. 

We got the temporary approval to get Todd's brother's appointments handled by the time they got to Cleveland on Thursday afternoon.  We are still having to deal with re-submitting any claims that were originally turned down between August 1 and August 18.  At least they are able to back-date the policy to cover us beginning August 1. 

All I could think about all week, was that we would have to reschedule the transplant.  Not only because of the lack of coverage, but because all the pre-transplant appointments wouldn't be done in time or within the allotted time leading up to the transplant.  The transplant is a process that takes multiple steps and perfect timing to achieve.  It is like a domino trick:  all the dominoes have to be lined up just right for everything to fall correctly.  For example, Todd has two more appointments before his admission date on September 7, 2014 to prepare for the transplant.  These appointments have to be done in a timely manner, just like all of the staging tests had to be done within a 30 day window of the transplant. 

This is obviously something that no one at his place of employment understood or cared about.  His boss called to try to apologize or offer money saying someone dropped the ball. While I tried to respond graciously, I wondered if he understood the emotional pain this caused.   Could anything he had to say relieve the tremendous amount of stress, anger, and anxiety that this "lapse" created for us?   A postponed transplant date would have so many adverse consequences: Todd would have to repeat all his testing, maybe get another round of out-patient chemo, his brother would have to postpone testing, and more importantly loss of time with our kids.  We knew it was already going to be a stretch to get home to be with our family before Christmas after the transplant (100 days), but when I thought we would have to postpone the transplant date, which would mean no Christmas as home, I was ready to cry.

I'm very thankful that we could get the insurance reinstated within the 30-day grace period, but I can't help wonder what would have happened if we didn't find out until after that time. It will take another week and some more phone calls, but hopefully we can get all the claims processed. I pray that we can get past our anger and give it over to God. I pray we can overcome evil with good.

“Vengeance is mine, I will repay, says the Lord.” ²⁰ To the contrary, “if your enemy is hungry, feed him; if he is thirsty, give him something to drink; for by so doing you will heap burning coals on his head.” ²¹ Do not be overcome by evil, but overcome evil with good.
-Romans 12:19-21

Pre-Transplant Staging Appointment: overview and nurse's visit Part 1

We drove up to Cleveland for two days of meetings and testing for Todd's staging pre-transplant.  The testing itself wasn't bad.  We breezed through most of  his appointments ahead of schedule.  While we don't have any of the official test results back yet, the heart tests looked good according to the technician.  He said there was a little leaking around one of the heart valves, but that most people have this issue.  The equipment used is just so sophisticated, that it sees every little detail these days.

They did take 19 vials of blood to run all the necessary blood tests, which seemed like a lot, but the phlebotomist's assured us that it is only equal to about a cup of blood.
Test results back on the lungs, bone marrow biopsy, and extensive blood work will be back in about a week.

I can't speak for Todd, whether he would agree, but I think the meetings with the bone marrow transplant nurse, social worker, and the insurance specialist was more overwhelming than the physical tests.

First, we met with the bone marrow transplant nurse.  We went over many of the items included in the 3-ring binder of information they mailed us months earlier.  As she walked us through the bone marrow transplant time frame and process, we began to realize what a difficult road lies ahead of us.  The most daunting information was learning about the toxicity and application of the chemotherapy medications and other drugs and their side affects.  He will be taking two intensive chemotherapy drugs to kill off his own bone marrow.  The first one will be Busulfan which will be given for give days, four (4x) a day, with each treatment lasting 2  hours.  The main side effects will be decreased blood counts, nausea, Mucositis, and Esophagitis, hair loss, discoloration of the skin and nails, possible seizures, and scarring of the lung tissue.  To combat the threat of seizures, they will give him an anti-seizure medication called Dilantin once a day while he is receiving the Busulfan.  We quickly caught on too that about every medication he will receive can cause diarrhea and/or upset stomach, so I won't repeat that side affect from here on out: it is a given!

Why all of those pre-transplant tests?  Not only were they taken to make sure Todd had no major health problems, but also to give his doctors a "baseline" to use for comparison in the future to detect damage to the lungs, liver, etc.  Since Busulfan can rarely cause the scarring of the lung tissue or Pulmonary Fibrosis, they will repeat a pulmonary function test one month after he is discharged from the hospital to monitor any damage or problems.

Mucositis and Esophagitis is when the lining of the mouth, gums, and the esophagus become inflamed and sore during treatment.  As a result, he might develop mouth sores, dry  mouth, sticky saliva, difficulty chewing or swallowing, or a burning sensation in his mouth or throat.  (Center for Consumer Health Information, 2013).

After the five days of Busulfan, Todd will receive two days of Cyclophoshamide also know as Cytoxan.  It too will be given through his cental venous catheter once a day for four hours.  Some "pre-medications" will be administered to help decrease the side effects.  The same type of side-effects will be possible with this drug too: decreased blood counts, Mucositi, Eophagitis, hair loss, discoloration of skin and nails plus additional side effects like: nausea, vomiting, loss of appetite, burning and/or painful urination, changes in tastes, dizziness, jaw pain, nasal stuffiness, and blood in the urine (hemorrhagic cytitis) and possible heart damage (cardiotoxicity).  (Center for Consumer Health Information, 2013).  To combat the possibility of blood in the urine, he will be given a medicine called Mesna/Menex intravenously along with additional IV fluids.  To prevent the cardiotoxicity from developing, he will have an EKG to monitor his heart before each dose of Cytoxan.

On day -1, the day before Transplant, he will receive no chemotherapy, but instead will be given a day for his body to recover somewhat.  The transplant will occur, likely in the  morning, on September 16, 2014.

If all of this isn't even to overload your mind, the nurse then went on to discuss all the other kinds of drugs he will be given to aid in the grafting of the new bone marrow, to fight viruses, bacterias and diseases, and to counter-act the chemotherapy side effects.

The next class of drugs are the immunosuppression drugs such as Tacrolimus, Mycophenolate Mofetil, and Cyclosporine.  With such an new and immature immune system, Todd will be susceptible to contracting infections, viruses, bacterial infections, and the most common disease after transplant: Graft versus Host Disease (GvHD).

Todd and I agreed to participate in a random clinical trial to determine whether he will receive the typical standard treatment of Methotrexate, a chemo drug used to prevent GvHD and Tacrolimus or a variation treatment that contains mini-doses of Methotrexate, along with Tacrolimus, and Mycophenoate. (I won't go into all the side-effects from these drugs now, or you too will feel the same scary feeling of overload that we did.) The trial is only used or continued if Todd is NOT showing symptoms of GvHD.  If he shows any symptoms at all, they terminate the study and continue with the standard treatment or whatever medication regime is dictated.  As a late note here: we just found out that Todd will be in Group B which will receive the mini-doses of the Methotrexate. We are happy to try this. Less toxicity exposure would be good!

Besides immunosuppressants, he will receive steroids with them to help prevent and/or treat GvHD and a host of others complications listed here:
Anti-viral drugs: Acyclovir, Valganciclovir (Valcyte), Ganciclovir (Cytovene)  Anti-viral drugs are given to keep him from subcoming to viruses, especially cytomegalovirus (CMV)
Anti-biotics: Amoxicillin and Ciprofloxacin
Anti-fungals like Fluconazole (Diflucan), Itraconazole (Sporanox) Posaconazole (Noxafil), andVoriconazole (Vfend).  Has to abstain from raking leaves, mowing grass, beer, woodworking, etc.  Anything that would expose him to spores for some time after the transplant.  
Immune Globulins (IVIG): under a variety of brand names, to help fight infections
(Again, too many drugs to discuss all the side effects).

While most of these drugs will be given intravenously while he is hospitalized, some are in pill form, and most will be prescribed in pill form after his initial discharge from the hospital.  Basically, we were told to go buy the largest pill container we can find! I have a medication chart that I can make copies of to help me keep track of the times he takes them all.

In addition to keeping up with his medications, I also have a chart to use to help me when I need to take his blood pressure and temperature multiple times per day once he is released.  Anytime he develops a fever of 101.4 or greater, I have to run to him to the Cleveland Clinic Emergency room since this is usually indicates the beginning of an infection.  

The nurse reviewed all the ways GvHD can manifest itself after transplant but I will save that for the next blog.  To be continued to Part 2. 

Transplant Date Scheduled

Before Todd's third round of chemotherapy we drove up to The Cleveland Clinic on July 9, 2014 to meet with his transplant doctor to discuss setting up the transplant. While the Vidaza had some positive results in lowering Todd's blast counts, we realized that this was no long term fix. We understand that some MDS patients receive monthly rounds of Vidaza for 12+ months or more, but many or most of these patients do not have a bone marrow donor match or their health is not stable enough to undergo a transplant.  We have accepted that this is not an acceptable treatment regimen for Todd.


Now that we are resigned to have the transplant, all the scheduling is set.  Staging, or the pre-screening testing that Todd needs to undergo with be done this Thursday and Friday, August 7 & 8, 2014.  During this visit, Todd will undergo a chest x-ray, lab work, bone marrow biopsy, an echocardiogram, an electrocardiogram, and a pulmonary function test.  In addition to testing we will meet with a transplant nurse, social worker, and an insurance specialist.  It is during this time that we can make housing arrangements for our extended stay once Todd is released from the hospital.  To get on the waiting list at The Hope Lodge, a nearby house for cancer patients, his social worker has to make the call. 

During this short overnight visit, we will be staying at a hotel about 20 minutes away from the hospital that gives bone marrow patients special lower rates (because The Cleveland Clinic helps to subsidize the rates) to gauge whether I will spend the nights there while he is hospitalized or not.  If I'm not comfortable being away from him, even for short periods, I may just stay in his room those 4-6 weeks.

 Todd's brother, his perfect match bone marrow donor, has also scheduled his Donor health screening for one afternoon at the Cleveland Clinic.  Todd's dental cleaning and assessment with our local dentist is also set.

I have included a scan of his calendar explaining how the days will be counted in terms of the transplant schedule.  On the day he is admitted, September 8, 2014, a count down begins (Day -9) until the date of the actual transplant, where he will have his brother's donor bone marrow injected, which will be considered Day 0 on September 16, 2014.  Those eight days: days -9 through -2 will be when he receives the intensive chemotherapy drugs that will kill all of his own bone marrow.  Day -1 will be a day of rest before the infusion on Day 0.  The transplant itself will only take about 20 minutes!  His brother will be there that morning to have his bone marrow harvested and then it will be brought up right away for infusion through his Hickman chest catheter.  This will likely occur in the late morning, since the donor is a family member (this makes the process happen faster than a non-related donor).  The days after the transplant will be counted in positive numbers: day +1, +2, etc.

Besides going up for staging this Thursday and Friday, Todd has an appointment on August 29, 2014 for lab work, an assessment, and a meeting with the pharmacist to go over the numerous medications we will be dealing with.  Another visit will take place September 4 and 5, 2014. The first day, Todd will have his Hickman chest catheter surgically inserted, and on the next day I will meet with the nurse to learn how to change the dressings, clean the catheter tubes, and care for the insertion site. 

Right now I am in the process of creating packing lists for me and Todd.  Since I'm not sure I will be able to come home during those 100 days, I'm debating whether to pack for the entire time or not (100 days).  We will be there beginning in the fall, but Cleveland can get colder in November and December.  I'm still figuring out how I will get important mail, whether to have it sent directly to the hospital or have my mom send it up to me in a batches from time to time.  I've got a list of special things I need to buy for Todd, like an electric shaver, since he won't be allowed to use a regular razor. 

In addition to creating lists for me and Todd, I am also preparing a list of things I will need to leave for my mom and a list of the girls' schedules and activities. 

I have had some ask about coming up to visit Todd or to bring the girls.  This would be nice.  I'm just not sure how much company he can have and when he can have it: pre-transplant, post-transplant, while in the hospital, or after he has been released.  This will have to be addressed when I have more information. 

Thank you for all the prayers and support.  We will really need them right now.  Things are a bit overwhelming with all the preparations that need to be made for our stay at Cleveland, the girls' needs here, and getting our oldest daughter moved into her college dorm later this month.  I will feel better once the girls get into their school routines before we leave. 

I'll post more updates after our visit this week.