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.
Dave