Dr. Whitley is an amazing guy. He's the geneticist we met with at the end of the day today. This guy knows his stuff, and is one of the pioneers in Hurler research. I had a whole list of questions for him, and he was patient with us, and stayed with us until well after 6:00. I'm sure he was expecting a quick 30-45 minute chat. We surprised him.
He was really impressed with Sarah and Jimmy, especially how much research they've done, and how informed they are. Essentially, the conversation boils down to one question: Should Gracie have enzyme replacement therapy (ERT) prior to transplant. I'll try to break down the options now, but it's hard when I can't draw pictures for you.
Option I - Transplant only. No ERT. Upside: Speed. Downside: We're trying to decide if the benefits of ERT make a difference. It takes about 10 days to find a donor for cord blood transplant. That means Gracie should be able to start chemo and transplant by the end of February.
Option II - Intravenous ERT for 8 to 12 weeks, then transplant. Upside: Potential benefits include rapid reduction in any potential peripheral problems, and better preparation of the pulmonary system for the chemo and transplant process. Downside: Delays actual transplant until Mid-April (2 months later).
Option III - Intrathecal ERT then Transplant. Intrathecal means they deliver the enzyme via spinal tap, directly into the cerebro-spinal fluid. Upside: More direct delivery mechanism, that should accelerate parts of recovery. Downside: Enrollment in this clinical trial is currently frozen. Apparantly, a child with Hurler-Scheie being treated on option III at UCLA died unexpectedly. Signs suggest that the death was not related to the intrathecal therapy, but until the full autopsy results are available (6 weeks) they are taking precautions by closing enrollment.
My interpretation: Sounds like ERT is great for bigger kids with Hurler-Scheie (a milder form of of the disease that presents later in life), since it helps with many of the non-neurological issues. ERT doesn't cross the blood brain barrier, so it doesn't correct the neurological deterioration - only transplant will help that.
According to Dr. Whitley, Option II (above) is primarily for kids who experience respiratory and pulmonary problems when they first present. Because Gracie was diagnosed so early (THANK YOU Dr. Cortez), she has no evidence of those specific problems. In other words, I'm leaning toward ERT being a "nice to have" and not a "need to have" for Gracie.
It doesn't seem like ERT will do any harm, but the question is, will it do enough good? In a nutshell, is it worthwhile to do ERT even though it will postpone the transplant by 10-12 weeks? We'd love your opinions and feedback here. We're having a difficult time with this particular decision.
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I vote for Option II - it sounds like this option would "prep" lil Gracie's body for further (and more successful) treatment. I know in my heart this lil girl is going to kick some Hurler butt (Gracie Balboa), this option will give her body a chance to get some "training" time in before the title fight...
Neat idea--injecting enzyme directly into the CSF, that would take care of the blood-brain barrier issue... still, I'm not sure there's reason to take that on either, if Sauce is a candidate for immediate transplant.
I'm still unclear about whether or not ERT, and the likely formation of antibody to the synthetic enzyme would have any affect on transplant. I have to assume that the chemo would take care of that.
Also, if she doesn't have any pulmonary/cardiac deficit, why the 12 week course of ERT? Is that protocol for the trial, or is it something she needs? And what is lost between now and April? We did discuss with Dr. Kurtzberg that MLS 1 is kind of slow-moving, but how much, if any, appreciable loss would be seen in neurological function in that much time? It might not be known, since it's hard to measure cortical activity sometimes in babies.
Anyway, if the specific risks to Gracie are not going to be improved by ERT, that is, if she's already healthy in the areas in which it's effective, I would consider a serious discussion with her team about the possibility of going ahead without it.
Just a discussion, mind you, not demands based on my half-baked understanding of the treatment protocol :-) I remember that Dr. Kurtzberg mentioned not giving ERT to healthy infants before transplant, and I think I recall the rationale being that, unless there was some necessity for beefing up her systems, it wasn't worth postponing HSCT to do it. (I'm not totally sure about that, though).
I don't envy you all--having to make such a big decision. I know your docs will be able to help!
xoxoxo
Sis
My holdout over the ERT decision has more to do with the recovery process rather than the BMT prep process. My feeble brain keeps trying to remember if someone here had mentioned that the ERT aids in somewhat protecting the pulmonary system (which I understand is the most vulnerable when immuno-suppressed) while we're waiting for her immune system to restart and also it would provide the missing enzyme to her body (but not her brain) while the new cells get started up. I need to talk to Dr. Orchard/Dr. Tolar about it again before I can truly weigh in on this.
And yes Mandy, the 12 weeks prior is part of the protocol.
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