ric

Day -6: Steady as She Goes

/ Evan / 2 Comments

So far so good with Fludarabine. No reactions, she is taking it about the same as she would a hydration drip, we have seen little to indicate she is even on a chemotherapy med this week.

Her counts have been ticking down a bit, but not as precipitously as they did on Campath. Fludarabine as mentioned previously is a general fast-growing cell suppressor, so it should be reducing all of her blood counts somewhat. Her white has been going down and that’s the primary marker the doctors appear to be tracking. Her Lymphocytes are holding at 2-3% depending on the day, and her platelets have remained high so far.

We’re a few days out now, and what we expect to be the worst of the conditioning lies ahead. Tomorrow Zoe is admitted, goes into surgery, and has her last dose of Fludarabine. Saturday & Sunday are Melphalan, the sore-inducing med, and Monday is Thiotepa, which requires 5x a day bathing to prevent chemical burns on the skin.

We’re hoping that things continue to go as well as they have. Zoe has been wonderful, and while we can’t quite expect an easy ride, we remain optimistic that the Reduced Intensity Conditioning will allow her to meet her count goals without major pain. After that, we’ll be focused on getting those counts up in the wake of the transplant on Wednesday.

Update: Counts back

[spoiler name=”Click to show counts”]

  • WBC: 1.2
  • Hemo: 8.9
  • Platelet: 513
  • Lymphocytes: 0
  • Creatinine: 0.2
  • Bilirubin: 0.5

[/spoiler]

All in all we’re exactly where we should be. Liver and Kidney markers are good, Lymphocytes mostly gone, WBC down where it should be.

Day -9: Fludarabine Starts

/ Evan / 5 Comments

Today we start Fludarabine, which is Zoe’s 2nd major chemotherapy medicine in the Reduced Intensity Conditioning (RIC) regimen. Fludarabine is designed to eliminate fast growing cells, any fast growing cells. Cells in the bone marrow are very fast growing so they are what will be most affected. Campath is a drug that specifically targeted Lymphocytes (virus fighting cells that are part of any normal immune system), whereas the Fludarabine will eliminate everything in the marrow. It may also finish off the last of her hair, but Maya was nearly bald until she was a year old, so we’re used to that.

It’s considered a well-tolerated medication, so we are hopeful that we won’t see anything at all this week, other than a drop in cell counts and perhaps some fatigue. So far that’s been the case.

Zoe’s counts came back up a bit over the weekend:

[spoiler name=”Click to see counts”]

  • WBC: 2.9
  • Hemo: 9.5
  • RBC: 3.12
  • Platelets: 730
  • Lymphocytes: 3%

[/spoiler]

We’ll continue Fludarabine until Friday. Also on Friday Zoe will get an additional Central Line placed, which means surgery. Hopefully the last major one.

We’ll be admitted to 5200, the Pediatric Blood and Marrow Transplant ward on Friday after surgery, and we will then begin the last medications before the transplant itself next Wednesday.

Zoe is handling all of this as well or better than we are. She’s a fantastic baby.

httpv://www.youtube.com/watch?v=OUK7rlXxYlk

Day -19: Finishing Up Campath

/ Evan / 7 Comments

Zoe has really impressed everyone around here, including her Mom and Dad, with her strength this week. We’re nearly done at this point, she’s half way through the last dose of Campath, and barring any problems it should be her last.

After yesterday’s unusual reaction, we’ve had a few more folks than usual pop in to take a look at her. It’s not everyday they see Harlequin Phenomenon, among her treatment team only her primary physician had ever seen it before as best we can tell. For the record, it is a harmless phenomenon, and it is not the same thing as Harlequin Syndrome, which is an unfortunate condition indeed.

Today’s counts look good:

[spoiler name=”Click to see counts”]

  • WBC: 4.5
  • Hemo: 10.5
  • Platelets: 22
  • Creatinine: 0.2
  • Bilirubin: 0.3
  • AST: 78
  • ALT: 48
  • Lymphocytes: 0

[/spoiler]

Because of her platelet count, Zoe will get a transfusion at the end of the day to get her through to Monday. This is not unexpected, the Campath knocks down the platelets along with her Lymphocytes. We’ll be checking in on Sunday to be sure the transfusion does what it needs to.

Next week we’ll be in 3 times for counts, but otherwise it’s a “break” week. Zoe will be on Hydroxyurea to keep her immune system suppressed until the following week when we start Fludarabine and Melphalan, at which point we’ll be admitted in the lead up to the transplant.

It’s been an amazing week. A relief to be starting treatment, sure, but more than that a relief to see Zoe handling everything so well. We still have a lot of anxiety about things, but it’s different now.

Often the anxiety in anticipation of the journey is greater than once the journey has started, and I believe that’s how we’re feeling right now. Glad to have started toward Zoe’s cure, and optimistic that we’ll reach our destination safely.

Afternoon Update:

Without even a whimper, we’re done. Things went so well I’m waiting for something to happen, but at this point there is little left that could. Very proud of Zoe, she’s weathered the week better than we could ever have hoped.

More on Reduced Intensity Conditioning, Cord Blood, and HLH

/ Evan / 3 Comments

A lot more information today. Some days it feels like we’re drowning in medical data and decisions. Michelle and I have been working through the options and doing our best to understand each path using our own research and what we learn from parents who have gone through this, which we then speak to our doctors about and clarify until we feel able to make a decision.

With regard to RIC, we’ve been going back and forth about using that or ablative/high-dose conditioning. One route is the more conservative route that has more successful cases behind it, but greater future danger for Zoe’s health and development. The other is much more modern approach with less patient data to point to, but can result in a very clean, relatively safe cure for Zoe’s condition.

We have pushed Dr. P and our nurse coordinator pretty hard for answers to every possible angle of this in the past few days. We’ve presented other cases of RIC/HLH/Cord Blood patients with very similar protocols but which were not successes and asked them to help us understand what will be different for Zoe. We’ve pressed them for examples of successes with this combination of factors. We’ve asked for numbers on Duke’s track record with this combination as well.

At this point we feel fully satisfied that, for Zoe’s case, for her current condition and the team of people treating her, RIC is the way we should proceed. It’s a tough decision, but this is the direction that feels right.

In recent years there have been a number of advances that will assist Zoe. The team at Duke was the first to do an unrelated cord blood transplant, and they do more than any other institution. That helps our confidence level as well.

Their process includes several additional medications to the standard protocol that help raise the chances of a successful graft, one of the concerns when using RIC with cord blood and likely a factor in the failure to graft in some patients in the past. They know now to continue GVHD medications longer than was once felt necessary, with past cases at various institutions proving clearly that stopping too early can cause the graft to fail.

What we’re seeing is that HLH is a relatively young disease and that, while the treatment phase is well established with the HLH-2004 protocol, the cure phase is still being perfected. This leaves a lot of fear and doubt, and the old saying that if you ask 5 doctors you’ll get 5 answers doesn’t help very much when it starts to ring true.

In the end we have to look at where Zoe is right now, and where medicine is right now, and do our best to make the right decision. Hopefully we have.

Reduced Intensity Conditioning & HLH

/ Evan / 6 Comments

We’ve decided to go forward with the Reduced Intensity Conditioning (RIC) for Zoe. As I mentioned yesterday, it came up again in conversation with Dr. M, and after a long meeting at Duke where we discussed both the RIC and the “normal” or Ablative conditioning, we felt pretty strongly that this was the right approach.

Let’s back up a moment.

In our first meeting with Duke, we asked about the potential for a RIC process after doing a bit of research, but we didn’t have any cases to look at which were similar enough to Zoe’s to know if it was something that would work with HLH. At that time the idea was dismissed for the most part, since it’s not how they have done things with HLH patients, and they have had a good track record with their process.

Since then, we’ve spoken with or read about a few different cases where HLH patients took this approach, so we decided to bring it up again for consideration. This time the response was extremely positive, in fact Dr. P felt that it was the best approach having spoken to colleagues and done additional research since we first discussed it.

We’ve rewritten the plan entirely at this point.

About RIC

Reduced Intensity Conditioning is a process traditionally used for patients who cannot handle the standard ablative (high dose) conditioning in advance of a Bone Marrow or Stem Cell Transplant. It often involves an entirely different set of medications designed to achieve the same goal, but with less damage to the body.

The goal of the conditioning is to prepare the bone marrow for the new cell material, either donated bone marrow or stem cells. If the transplanted material does not take or “graft”, then the process has to be repeated or restarted.

Different diseases require different levels of conditioning. Some require the high dose or ablative conditioning to ensure that the disease is wiped out in the body before beginning. Others, such as immune disorders or non-malignant diseases, might require less intense conditioning since there is not something that has to be eliminated, rather the bone marrow is being prepared for new cell material. Partial elimination might be enough in these cases.

In short, ablative conditioning completely wipes out the bone marrow. RIC can either partially wipe it out, leaving some material but making enough room for the new transplant material, or completely wipe it out, giving the same results of the ablative therapy without the additional risks.

Advantages and Disadvantages

The advantages of RIC are numerous. For starters, all of the disadvantages of normal high-dose conditioning are reduced or eliminated.

  • The patient has less increased risk of future malignancy
  • Higher chance of remaining fertile
  • Reduced damage to the organs
  • Less chance of growth retardation and/or puberty delay

Disadvantages are few.

  • Chance of needing to repeat or restart the transplant procedure if graft fails
  • Longer conditioning process
  • Chance of relapse with some conditions or diseases

So why not do RIC? Well, a patient may not qualify for it due to their disease, or they may prefer to take a more conservative approach. RIC is newer and less tested, and the process is still being refined. Traditional conditioning is well tested and established, and it is a more sure approach in terms of the graft.

RIC and HLH

RIC has a relatively short history with HLH so far, due in part to the relative immaturity of HLH research. There are studies, and in some transplant hospitals they do RIC with HLH, but keep in mind that there are very few HLH patients in any given year. This makes it hard to accumulate results.

What sporadic results there are have been fairly positive, as best I can tell. Outcomes seem to be as good or better than ablative conditioning, and Dr. P confirmed our impressions in our discussion. Dangers still exist with any transplant: Graft Versus Host Disease and risk of infection are the two biggest and are no less dangerous on RIC.

Most of the existing studies I was able to find do not use cord blood stem cells as the transplant material however, making the specific combination of Unrelated Cord Blood, RIC and HLH exceedingly rare.

Zoe will be the first HLH case treated with RIC at Duke. They have treated numerous other conditions with RIC however, and the process is very similar. The medications are all well tested and established. The precautions are all in place for GVHD and infection as they would be in any transplant situation, and the team at Duke is great.

What does this mean for Zoe?

Zoe is in about as strong a position as any child could be going into a transplant with HLH. Her organs are in good shape, she has no fever, no other known infections. If there were ever going to be a successful case to do RIC with a cord blood transplant in an HLH patient, we like to think that Zoe is it.

This is a more modern treatment and gives her the greatest chance of walking away from this unscathed. I strongly suspect that HLH will be treated with RIC increasingly, given what I’ve been reading about the results. There just doesn’t seem to be a significant downside.

Worst case scenario related to RIC, she doesn’t graft and we have to start over with conditioning and a new transplant. Obviously GVHD and infection present other worst cases unrelated to the conditioning process.

This means we’ll be starting Zoe on Campath in a couple weeks in the outpatient clinic. After a week of that, she’ll have a week off, then we start the heavier chemo medications and Zoe will be admitted.

Our optimism is now at it’s highest point since we began this journey. We still have a hard path ahead, but we feel better than ever that we’re getting the best treatment we can for Zoe and that our advocacy is working in her favor.