Acute Myeloid Leukemia with MDS Diagnosed; Treatment Decided Oct 4, 2016

 Induction chemotherapy -

Chemotherapy given to induce a remission. 

      This term is commonly used in the treatment of acute leukemias.     Chemocare.com 2002-2016

After 6 days at MD Anderson Cancer Hospital, the doctors finally had enough information from the test results to make an official diagnosis and propose a game plan for treatment.  On Tuesday, October 4, 2016, Dr. Benton came by in the morning with the much anticipated bone marrow results.  Todd's blast counts were at 21% which officially puts him into the diagnosis of MDS with Secondary Acute Myeloid Leukemia (blasts > 20% in the bone marrow).  While the full genetic panel was not back, the bone marrow flow cytometry report revealed a positive major genetic mutation marker known as CD56, also known as NCAM1, Neural-Cell-Adhesion-Molecule 1.  This mutation stems from a translocation of the 8 and 21 chromosomes [t(8;21)].  Having this mutation puts Todd at risk of the Leukemia infiltrating the blood/brain barrier and entering the central nervous system.  The Transplant Fellow explained it as follows:  There are very few or no cells in the spinal fluid sac that surrounds the brain and spine.  You usually don't find any white or red cells in there.  With this mutation, the blast cells CAN penetrate this barrier and can be found in the spinal fluid.  AS A PRECAUTION, they will do a "lumbar puncture" or spinal tap to collect spinal fluid for testing, to see if it tests positive for blasts.  As an additional precaution, they don't wait to get the results back to treat this area.  Instead, they need to replace the fluid they remove with something else to avoid a spinal headache, so they insert a type of chemotherapy into the spinal fluid to kill any potential blasts cells there.  Of course, we already know that Todd has the TP53 genetic mutation that makes it more resistant to treatment and he has the IDH1 mutation. 

To treat the AML, Dr. Benton and his colleagues recommended using a study trial regimen available only at MD Anderson. (Trial #2012-1064).  Instead of the standard of care treatment given everywhere else, known as the 7 + 3, where they give 7 days of cytrabine and 3 days of daunorubicin, they will use four drugs in a 5 + 5 day trial treatment called Decitabine + CIA. 

The first 5 days they will give him a drug called Decitabine a Hypomethylating Agent (HMA) used to prime the leukemia cells to accept the other drugs.  Then they will give the CIA:
Clofarabine 5 days, Idarubicin 3 days, and Cytarabine (Ara-C) 5 days.  The Idarubicin is given less days because it poses the most toxicity, especially to the heart. 
According to the Trial information posted on clinicaltrials.gov, the following regimens are possible:

Drug: Decitabine     Purpose:

Other Name: Dacogen (DAC)

Purpose: Designed to damage the DNA (the genetic material of cells). This may cause cancer cells to die. 

Phase I and II - 20 mg/m2 by vein daily for 5 days (days 1-5)

Drug: Clofarabine

Other Names:

• Clofarex
• Clolar

Purpose: It is designed to interfere with the growth and development of cancer cells.

Phase I Starting Dose - 15 mg/m2 by vein daily for 4 days (days 6-9)

Phase II Starting Dose - Maximum tolerated dose from Phase I (number of days selected based on Phase I portion).

Drug: Idarubicin

Other Name: Idamycin

Purpose: Designed to damage the DNA (the genetic material of cells). This may cause cancer cells to die. 

Phase I and II - 10 mg/m2 by vein daily for 3 days (days 6-8)

Drug: Cytarabine

Other Names:

• Ara-C
• Cytosar
• DepoCyt
• Cytosine Arabinosine Hydrochloride

Purpose: Designed to insert itself into DNA and stop the DNA from repairing itself.

Phase I and II - 1 g/m2 by vein daily for 5 days (days 6-10).  Clinicaltrials.gov, 2016.

                    

We have not been told whether he will be part of Phase I or .  The whole intention of this "induction" chemotherapy is to get the Leukemia into remission.  The most upsetting revelation of this remission is that with AML, remissions are short-lived, and each time there is a relapse of disease, another remission will be harder to achieve and will be of a shorter duration.  The first remission after the first induction usually lasts <6 months.  According to Texas Oncology, "If a complete remission is achieved and no further therapy given, over 90% of patients will have a recurrence of disease in weeks to months."  (Texas Oncology.com 2016).  Because of this realization, we have agreed with Dr. Benton that Todd will have this induction with the intention of pursuing a Second Bone Marrow Transplant as soon as possible. 

It can be difficult though to get a non-related donor lined up in a short period of time.  When Todd had his first transplant, he was fortunate to have a perfect match with his brother Tom.  However, since Todd relapsed so quickly after the transplant, they would rather use a non-related matched donor this time.  Dr. Benton brought in a transplant doctor and a fellow here at MD Anderson to consult in the matter.  They came by today to discuss transplant options.  It was his opinion that finding a non-related donor from the National Bone Marrow Registry who would be ready to donate, (Be the Match) may take up to 3 months!  It was his opinion that we did not have that long to wait if at all possible. 

After the first induction, they like to wait for the bone marrow to recover but not long enough for the cancer to return.  In this case, they could do a second round of chemo called "consolidation" until the bone marrow donor is found and ready to donate.  For this reason, he was very interested in screening our three kids to see if one of them would be a haplomatch (half full match).  Abby, was screened at registered when S.A.M./Sharing America's Marrow came to the University of Cincinnati to recruit donors during her freshman year.  She actually volunteered with Sam and her sister during their visit. 

Consolidation chemotherapy -

Chemotherapy given once a remission is achieved. 

The goal of this therapy is to sustain a remission. 

Consolidation chemotherapy may also be called intensification therapy. 

This term is commonly used in the treatment of acute leukemias. Chemocare.com 2002-2016

We would have the option to have the transplant here at MD Anderson or back at the Cleveland Clinic.  However, traveling after induction can be risky.  In addition, MD Anderson has more options here than Cleveland does.  They may have different pre-transplant conditioning and/or suppression therapy after transplant than Cleveland.  Also, if Todd was to relapse once again after transplant, there are more trial and treatments options here for him.  For this reason, we have asked Dr. Hamilton at the Cleveland Clinic to transfer the donor search from there to here.  The team here will continue the search, including sending screening kits to our three children. 

I took Todd downstairs today to the MD Anderson Hair Salon for Patients.  He wanted to have his head shaved before starting the chemotherapy.  The Salon is ran by the Volunteer Services Department, but the wonderful hair stylists there are paid by the department.  They will wash and style hair, or trim or shave hair and they assist with wig selection and styling.  Todd is still handsome without his hair!

After getting the insurance approval today, the trial nurse came by to discuss the treatment with us and have Todd sign the consent.  We knew we would work well together when she asked Todd if he was a Bengal's fan!  Her husband is from Cincinnati and she has been converted too! 

The thing I found the most upsetting when discussing Todd's treatment was the topic and discussion of putting Todd is "Protective Environment" after the first round of chemotherapy induction.  It is something that is only done here, because they have always done it this way.  They gave us two options: the Protective Environment or Discharging him on the Fast Track.  From one extreme to another.  PE is when they put patients  50 years or older with AML just off of induction therapy in a special room for over 20 days, where there is no bathroom, a special HEPA filter, no family allowed inside, etc. to help protect the patient from getting infection and being able to detect and treat a fever or infection right away.  I would only be allowed to come visit in a visitor's room connected to Todd's room where I could speak to Todd only through a glass window between.  I could not touch him or help him.  But, doctors, nurses, cleaning people, and the food service people would be allowed to come and go with proper attire (shoe covers, protective clothing covers, masks, and gloves) but not any family!   There is no real research or data that "proves" that PE is more effective. Even though Todd is only 47, he is close enough in age for them to think PE was a good idea.

I thought it was a bad idea, because of the lack of mental and physical support the isolation would cause.  Todd and I have been through a lot together and I can't imagine not being there to help him, comfort him, hug him, and encourage him.  He felt the same way.  If he goes into transplant after treatment, he will have to stay in the hospital another 30 days. 

On the other spectrum, the Fast Track program would allow Todd to be discharged right after chemo induction and then he would have to return every two days for treatment like transfusions, check-ups, etc.  We would have to stay within 10 minutes of the hospital in case Todd spiked a fever over 100.9; he would have to brought in within 30 minutes even if it was just a neutropenic fever and not an indicator of an infection.  Apparently, an infection can take hold fast. Any fever over 100.9 would always necessitate being admitted.  It is not uncommon for these patients to be admitted several times during the Fast Track process.  He would have to be readmitted at some point when the transplant conditioning begins and/or if consolidation therapy was needed (not sure about this). 

This made the decision difficult.  Finally, we got a social worker to come in and talk to us.  She said that we had the right to say what we wanted to do and that some patients in the past was able to do a "modified environment" where we could just stay in a regular room like now on the leukemia floor.  She said she wishes she would have been here when the doctors were rounding and she could have told them of this other option.  Today, when the doctors rounded, we just told them that we didn't want Todd to go to PE; instead we preferred a modified environment.  So, hopefully, this has been accepted.  We will see. 

The social worker gave me a substantial list of places to stay nearby.  I have to start calling right away to get on several waiting lists.  Even if we don't do the Fast Track option, we still will need housing post-transplant. 

I know I am probably forgetting to include so many other things but that is all I have time to blog now.  I will say that Dr. Benton hopes that the size of Todd's spleen could start going down soon after he begins the induction therapy.  This would be a big bonus!  He would be able to get off some of the major pain medicine he has been on the last couple of weeks, just to cope with the pain of the enlargement. 

It is late, and Todd was able to start his first round of Decitabine tonight about 9:00 p.m. DAY 1 Cycle 1. They started him on 42 mg (amount adjusted according to Todd's weight) at 50 ml/hour.  No transfusions were needed today, Wednesday October 6, but he had one unit of blood yesterday, Tuesday, October 5, 2016. 

References:

Chemocare.com  2002-2016.  "Chemotherapy Terms." Cleveland Clinic. Web. Retrieved from: http://chemocare.com/chemotherapy/what-is-chemotherapy/chemotherapy-terms.aspx

ClinicalTrials.gov.  April 26, 2016. "Decitabine Followed by Clofarabine, Idarubicin, and Cytarabine in Acute Leukemia." Trial Identifier: NCT01794702.  Web.  Retrieved from: https://clinicaltrials.gov/ct2/show/NCT01794702

Texas Oncology.  2016. "Acute Myeloid Leukemia Induction; Overview".  Web. Retrieved from: http://www.texasoncology.com/types-of-cancer/leukemia/acute-myeloid-leukemia/acute-myeloid-leukemia-induction

University of Texas, MD Anderson Cancer Hospital Webpage.  2016.  Trials.  "Study #2012-1064 Phase I/II Study of Decitabine (DAC) followed by Clofarabine, Idarubicin and Cytrabine (CIA) in Acute Leukemia." Retrieved from: https://www.mdanderson.org/patients-famiy/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2012-1064.html