I agree completely with the analysis by Beppe. This is a very difficult case made more difficult by the limitations in available therapy. Ideally in this case of CML-BC, I would try to evaluate for mutations which might transiently direct therapy. In the absence of a second line option, I would still go with involved field radiation and in the absence of other evidence of systemic disease, take this patient to an allograft. If systemic disease becomes evident, go with induction chemotherapy such as Beppe suggests and then proceed with allografting if an option is available.

The case that you present is a very difficult case to treat without a second or third generation TKI. First, if possible, I would suggest to perform the search for mutations on the materials obtained during the biopsy, just to know if there are mutations. This would be very relevant in case of the availability of a second or third generation TKIs, in order to decide which would be the best TKI to be used in association with cycles of chemo (AML like regimens as FLAG-Ida or similar). It is of course less relevant and almost redundant if you cannot use TKIs other than imatinib (that in this case should not be used as the blast clone has been proven to be resistant to it). In the latter case ( lack of a second or third generation TKI) I would add 2 or 3 cycles of chemo to radiotherapy- Then the patient theoretically should be moved to allo Stem Cell Transplant (even haplo if a full compatible sibling or MUD donor cannot be found), after having achieved at least haematological remission. However, if this approach cannot be performed, the only option remains chemo as I do not think that local radiotherapy could be enough to overcome the blastic clone, even if at the moment the bone marrow does not seem involved.

I hope to have understood well the situation of this patient and I remain at your disposition for further problems. Yours, Beppe

We present a 53 year old Mexican female with CML (Ph positive) in chronic phase since diagnosis in November 2014. Stratified as SOKAL low risk and was currently under treatment with Imatinib 400mg QD. Rest of PMH is irrelevant. Patient achieved major molecular response (MMR) and since September 2016 is undetectable, with a sustained response until July 2018 when we reduced the dose to 300mg QD; in May 2019 presented a molecular response relapse that required a dose adjustment to 400mg QD. The last RT-PCR is on January the 13th 2021 with a result of 0.067%, however, patient complains of pain in anterior thorax and a right parasternal palpable mass of approximately 4 cm by 3 cm. Biopsy was performed and revealed an immature haematopoyetic neoplasia with the following immunophenotype: CD45 + / c-myc + / MPO + / CD 34+ / CD117 +. Pathology reports are compatible with immature extramedullary myeloid tumor.

We know that this has been considered as a blastic transformation, even though it comes to our attention that the bone marrow is in molecular remission. Local radiotherapy has been prescribed because we do not have access to second generation TKI.

Your opinion would be greatly appreciated.