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Topic History of: High BCR-ABL levels after treatment of CML-BC

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  • Nobuko Hijiya
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2 years 11 months ago
High BCR-ABL levels after treatment of CML-BC

I am sorry to hear the teenager has had a difficult clinical course. As you know, in the current EsPhALL/Children’s Oncology Group study for Ph+ ALL, MRD assessment is done using IgH/TCR PCR and BCR-ABL1 PCR is not used for clinical decision making. Having that practice, I would send the patient to BMT now. You said donor options are not good. If he was here with us, we would take him to BMT with haploidentical donor (likely a parent). Is it an option at your center? If this is CML blast crisis, not Ph+ ALL, my approach would be the same. Although children with CML in advanced stages seem to do better (Eur J Cancer. 2019 Jul;115:17-23), BMT would give him the best chance. Switching to ponatinib was appropriate. Serious cardiovascular events that are seen in adults have not been reported in children so far (Br J Haematol. 2020 Apr;189(2):363-368) but Phase 1 studies are ongoing. If he needs to continue TKI and is truly resistant to ponatinib, empirical switch to other TKI like nilotinib or bosutinib may be an option, but I am not sure about it. Again, I think BMT now with negative IgH/TCR PCR would be the best option.

2 years 11 months ago
High BCR-ABL levels after treatment of CML-BC

We would like to discuss a 16-year old boy, diagnosed in 2006 (age 2y) with Ph+ALL (BCR-ABL p190). Treatment according to the EsPhALL-protocol, treatment-arm without imatinib (until 2008). No donor available.

In January 2018 (age 13y) “relapse”/second episode Ph+ALL (CNS2) was diagnosed. Underlying CML?

Treatment according to the EsPhALL-protocol with imatinib and dose-reduction of antracyclines (cumulative-dose>500 mg/m2), without SCT. TKI-therapy was switched to dasatinib (more potent/better CNS penetration). Excellent response with negative MRD IgH/TCR at end of consolidation.

However, BCR-ABL levels stayed high (between 2-6*10E-2=2-6%), without morphological/immunophenotypical aberations in PB/BM. BCR-ABL is present in myeloid cell fractions, indicating underlying CML.

As BCR-ABL levels stayed high, patient was switched to ponatinib (Phase I/II study), without any effect on BCR-ABL levels. Ponatinib was stopped after a few months. BCR-ABL levels are thus far stable without TKI-therapy. TKI mutation analyses was not performed yet. Regular Ig-rearrangement PCR is negative (no Ph+ ALL cells detectable).

In summary this patient probably has CML with already two-times a blast-crisis (2006/ 2018). How to approach the stable BCR-ABL (p190) levels around 2% without signs of hematologic/cytogenetic relapse?

He has a very poor donor so SCT would be a high-risk approach.
Currently we are employing a watch-and-wait strategy.

We would like your advise.
With kind regards,
Michel Zwaan & Maaike Luesink
Prinses Máxima Center for Pediatric Oncology