Translate page

× To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion (no more than 200 words) by posting it in this forum ("New Discussion" button below). Please include the country of origin.

Each clinical case will be forwarded to the expert clinical panel for a brief independent response. Consideration should be given to patient confidentiality. Details that are not critical to the case can be changed to preserve anonymity. Please consider including your email with the case. This will not be posted on the website, but is useful should further details be requested by the moderator.

As a full clinical history is necessary for accurate comment, cases and comments on the Forum are ONLY ACCEPTED FROM PHYSICIANS. If individual patients have a specific question we encourage them to contact their healthcare provider. General questions can be emailed to

DISCLAIMER: The iCMLf does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this Forum is solely at your own risk.

High BCR-ABL levels after treatment of CML-BC

2 years 5 months ago #1831 by maaikeluesink
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
  • Nobuko Hijiya
  • Nobuko Hijiya's Avatar
2 years 5 months ago - 2 years 5 months ago #1835 by Nobuko Hijiya
Replied by Nobuko Hijiya on topic 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.
Last edit: 2 years 5 months ago by arlene.
Moderators: Nicolaarlene