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Pediatric patient on Dasatinib

  • Nobuko Hijiya
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9 years 4 months ago #226 by Nobuko Hijiya
Pediatric patient on Dasatinib was created by Nobuko Hijiya
Dear colleagues,

A CML patient of mine is a 10 yo male. He was diagnosed 21 months ago at 9 yo of age with CML in chronic phase. He started Dasatinib 60 mg/m2 daily and has tolerated very well. Cytogenetics was 50% afgter 3 months, but he achieved CCyR by 6 months. At 18 months, PCR showed 0.35% by IS and at 21 months, 0.27%. He has a mutation (c.1423_1424ins35)which is not known to cause resistance to TKIs. His only sister is HLA-matched 10 out of 10. The question is whether we continue Dasatinib or take him to HSCT. I would appreciate your input.

Best regards
Nobuko

Nobuko Hijiya, M.D.
Associate Professor of Pediatrics
Northwestern University Feinberg School of Medicine Hematology, Oncology and Stem Cell Transplant Ann & Robert H Lurie Children's Hospital of Chicago
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9 years 4 months ago #227 by tim
Dear Nobuko

Your young patient had a poor response at 3 months but was on target by 6 months. After 21 months of dasatinib he is close to MMR but not quite there. His risk of transformation is probably very low. Adult patients receiving imatinib who were in this category of molecular response (0.1% to 1% at 18 months) had a 4% probability of progression over the following 5 years - less than 1% per year. If this were my 18 year old patient I would continue to monitor closely, consider whether the dasatinib dose is currently adequate and whether drug adherence can be improved but I would not consider an allograft unless there was definite evidence of loss of response.

The reference for the landmark analysis comes from the Blood paper:

Hughes TP, Hochhaus A, Branford S, Muller MC, Kaeda J, Foroni L, Druker B, Guilhot F, Larson RA, O'Brien SG, Rudoltz MS, Mone M, Wehrle E, Modur V, Goldman JM, Radich JP. Long term prognostic significance of early molecular response to imatinib in new diagnosed chronic myeloid leukaemia: an analysis from the international randomized study of interferon versus STI571 (IRIS). Blood (A*) 2010 116:3758-3765

What do pthers think? Any other opinion is greatly appreciated!

Best regards
Tim
  • John Goldman
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9 years 4 months ago #229 by John Goldman
Replied by John Goldman on topic Re: Pediatric patient on Dasatinib
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.
  • Jorge Cortes
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9 years 4 months ago #230 by Jorge Cortes
Replied by Jorge Cortes on topic Re: Pediatric patient on Dasatinib
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
  • Jerald Radich
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9 years 4 months ago #231 by Jerald Radich
Replied by Jerald Radich on topic Re: Pediatric patient on Dasatinib
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
  • Pankaj Malhotra
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9 years 4 months ago #232 by Pankaj Malhotra
Replied by Pankaj Malhotra on topic Re: Pediatric patient on Dasatinib
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
Moderators: Melissa Davis-Bishop