What is happening today

As a little further explaination of Brooke's previous post I will talk about what exactly we are hoping for. We previously stated that the survival for children with AML was around 65% which is what the doctors told us. In fact, survival is measured in two different ways, and for this cancer just counts out to three years. First, there is overall survival which means that you are still alive at three years. The chance of overall survival at three years is actually 71.1% with half occurring by 292 days. The other measure of survival is called event-free survival. This means that no disease-related event occurs within the three year time frame. An event would be something like recurrence of the disease (this is bad). The chance of event-free survival (EFS) is 63.0% and half of these occurred within 191 days.

Now this isn't really the end of the story. Her survival very much depends on the specific mutations causing her AML. She is missing some of the dangerous ones, but also has some of the dangerous ones. She is also young which has a higher success rate that kids over 10 years old. However, it is generally hard to combine all of this information into a better prediction of her survival. This is where the test that she is having today comes into play.

The study that I am getting all of these numbers from showed that the most predictive measure of her survival is something called minimal residual disease (MRD)*. MRD represents the percent of leukemia cells remaining after the chemotherapy is over in a sample of mostly normal (hopefully) cells. In this study it was shown that bone marrow MRD at day 22 after induction I (her first round of chemo) can significantly separate between a high risk and low risk group (p < 0.0001). So today they are taking a sample of Clara's bone marrow and looking to see what percent are still leukemic and what percent are normal.

In an ideal world, the chemotherapy would have worked perfectly and there would be no leukemia cells left. In fact, it used to be that the tools used to measure MRD were so crude that they wouldn't be able to measure the number of cells left. In the study I am referring to, they were able to measure as small as 1 out of 1,000 cells (so a minimum measure of 0.1%). In the current study they are able to be more accurate and measure as small as 1 out of 10,000 cells. The improved accuracy will help stratify the treatments more in the future but may not really help us now.

Like I said, the previous study showed that MRD was highly predictive of survival. They showed that if the MRD was less that 0.1% (the minimum of their measurement range) then event-free survival was actually 73.6% and overall survival was 80.5%. If the MRD was between 0.1% and 1% the event-free survival was 65.9% and overall survival was 74.3%. If the MRD was greater than 1% then the event-free survival was only 32.1% with overall survival at 44.5%.

Obviously we want the smallest amount of residual leukemia cells in her bone marrow. The sample is taken today but is then sent to St. Jude for testing. We should have the results early next week. If the MRD is high they may skip chemo and move straight to bone marrow transplant. If it is low, we have more rounds of chemo ahead to make sure that every single leukemia cell is dead.

* Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D. Lancet Oncol. 2010 Jun;11(6):543-52. Epub 2010 May 5.