Thanks Nobuko for clarifications. I think the debate about treatment in this kid is on the following parameters

1. Long-term adverse effects (known and unknown) of TKI vs risk and long-term adverse effects of allogeneic stem cell transplantation.

2. Applicability of adult data on pediatric patients (as quoted by Dr. Tim and Dr. Jorge)

I would put my humble bet on close molecular monitoring of the kid and keep option of transplantation in the reserve.

Regards

P

Dept. of Internal Medicine
PGIMER, Chandigarh, India.

First of all, I want to thank everyone for input.

To answer Pankaj’s question;
1. What was the Sokal score at presentation?
He was in intermediate by using Sokal score. However, it is very important for us to remember that Sokal score or other scoring systems have never been validated in pediatric population. I hope we will have data to validate or modify it in the near future.

2. When and why was the mutation testing done?
Mutation analysis was done a couple of times. First, at 3 months when cytogenetic response was not favorable and second time at 15 months when bcr-abl PCR increased a little from 12 months (two times).

3. How's the support of family members?
They are great. They are very intelligent and highly capable people. I have no doubt about their compliance.

4. What is the age of HLA matched sister?
Two years younger than the patient.

Not only the issue of scoring systems I mentioned above, there are many pediatric specific issues in CML that we need to work on. That includes children’s much longer life expectancy, better tolerability to HSCT and unique morbidities. Suppression of bcr-abl for 10 years as done in 70 year old patients may not be the best approach for children. We are getting more and more data on growth failure by long-term use of TKIs.

We are about to open a CML study in Children’s Oncology Group (COG). Although the number of children with CML is much smaller than adults, this study will provide important information. Also important is establishing standard care for children with CML.

We are also working on a retrospective study using a large dataset from CIBMTR to evaluate long-term outcome of HSCT.

We are working hard to improve the outcome in children with CML. Thanks again.

Nobuko

Hi

I have only questions on this patient..

1. What was the Sokal score at presentation?
2. When and why was the mutation testing done?
3. How's the support of family members?
4. What is the age of HLA matched sister?

Thanks

Pankaj Malhotra

I would worried about this child because of the poor early response, and his young age-we want to go for a cure in this case. That being said, he has responded pretty well (though I would hope for a lot more). I would guess that in his remaining years he will progress, but who knows when-Next year? Next 30 years? Given transplantations side effects on growth and sterility, I would try to keep him on DAS, and watch him like a hawk. We have a real advantage in that a donor is waiting in the wings, and presumably be mobilized quickly. If his PCR climbs significantly, I would probably move to transplant rather than trying to salvage with another TKI.

Jerald Radich, MD
Clinical Research Division
Fred Hutchinson Cancer Research Center

Thanks. I actually agree with Tim. Let us not forget that no MCyR or >10% at 3mo is worse, but still at least 80% of these patients will do well in the long term, so we are really talking about a small percentage who do “poorly”, and most of these can be rescued. Our data, presented at ASH, shows that those who by 6 months have caught up have a prognosis that is nearly identical to those with good response at 3 months. So I think this patient is doing well and I would not change therapy. Of course, proper monitoring is indicated.

Jorge Cortes

NB

I thought about this story for some while but at first without the data that Tim cites. I must say I do not know the correct answer but in the end I came up with the opposite view from Tim. I thought that in view of the 'suboptimal' response at 3 months and the facts that you don't have an MMR now and also his young age, which is of course good factor for transplant, I would probably proceed to offer transplant. I am not sure of the difference between age 10 and age 18, but perhaps one should do the transplant earlier rather than later .

Best wishes

J.