Saturday, April 18, 2015

The t-cells are in production

Hey all,

Wanted to bring everyone up to speed on Luke..  Novartis is going to being production of Luke’s T-cells on April 15th.  It’s a three week process so Luke is scheduled to be back in Kansas City to have lympho-depleting chemotherapy from April 27th through May 1st.  The therapy includes 3 days of fludarabine and two days of cyclophosphamide which he will get as an outpatient.  Expectation is for him to get his infusion of T-cells May 6th.  He will need to then stay in KC for 4 weeks after infusion for observation and treatment as necessary. 

This time between his enrollment and infusion has been a balancing act – they want to give enough chemotherapy to prevent the leukemia from progressing but minimize the potential of organ toxicity, like decreases his liver or kidney function, and depleting his blood counts putting him at risk for developing an infection prior to treatment.  

After infusion one the concerns is cytokine release syndrome (CRS).   When T-cells encounter a foe, they unleash cytokines, proteins that aid in and regulate the immune response. When T-cells get infused and multiply rapidly oncologists have seen a cytokine “storm,” a dangerous release of the proteins. They also will watch for tumor lysis syndrome, which occurs when a massive amount of dying tumor cells release metabolites that build up in the kidneys.

According to the doctors there seems to be an association with disease burden and CRS (more ALL, more CRS), but nothing definitive.  They did do a pre-T-cell infusion marrow biopsy as part of the phase I protocol but they didn’t put that in the Phase 2 trial as they don’t think there is a definitive correlation between an amount of disease  counted on a slide or in a machine and the degree of fever, renal problems, liver or lung problems, etc.  If leukemia blast cells are high prior to T-cell infusion they think you might be able to generalize that there is a higher probability of CRS but at this point they have no way on knowing what level of CRS to expect. 

The doctors do feel the management of CRS is usually pretty good.  The initial patient at Children’s Mercy experienced no fever, no CRS and is over 4 months out with remission.   

Luke’s will be a CD19 CAR T-cell recipient.  Both the leukemia cells and B-cells (another form of white cells in the body needs to fight infection) carry the CD19 protein that the CAR T-cells attach to.  The CAR T-cells don’t discriminate between the leukemia and good B-cells so both are killed off.  If the CAR T-cells do their job and stay around as long as they likely should, Luke will probably need IVIG for the rest of his life to compensate for his lack of B-cells. If Luke’s B-cells begin to show signs of recovery the concern is that that relapse may not be far behind. 

If you watched the PBS special on cancer leukemia and T-cells were front and center.  It was hard to watch the first of the three segments as it was so much of what Luke has been through revisited. 60 Minutes recently did a segment on the success they have had using t-cells on solid tumors and HBO had a special that highlighted the CART trial.     

if you are interested there is a lot of info on the internet on T-cell therapy.  Below are links to a couple of the articles I found good.  One of the articles is heavily technical the other is more of a magazine general knowledge article that provides a good overview of the theory, process and issues. 

That’s it for now.  Luke is feeling pretty good and getting his annual fill of crawfish.  He is scheduled for a few more rounds of chemo but nothing like he has received in the past.

As always your thoughts and prayers are appreciated.


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