I totally agree with Michele's and Jeff's opinions

I agree with Dr. Baccarani, it would be very important to get a cytogenetic/molecular verification of a Ph+/BCR-ABL1+ sarcoma.

Almost 10 years ago we had a somewhat similar case on high-dose imatinib 800 mg/d with multiple spontaneous fractures in the hip and a histological diagnosis of a granulosarcoma. Due to the necrotic nature of the lesions, no proper cytogenetic or molecular verification could be done. The patient was treated with dasatinib (was not eligible for alloHSCT) and extensive hip replacement surgery, slowly recovered and has been in CMR for many years now.

I would do exactly as Dr. Baccarani suggested; if you get a verification of a BCR-ABL1-positive tumor (or are unable to do the examination), alloHSCT. Otherwise 2nd gen TKI with very careful follow-up.

Kimmo Porkka

A progression to granulocytic sarcoma on therapy is part of the definition of blast phase. There is a very high likelihood that the radiation alone did not deal with the problem and although the switch to dasatinib may help with temporarily with disease control, she will very likely progress again. I would suggest allografting as soon as possible, before she again loses repsonse and therapy necessary to get her into a transplantable state becomes more intense.

This is a very rare case of CML developing a granulocytic sarcoma, that is an equivalent of a blast crisis, when the patient was in optimal response. I have never seen such a case in more than 40 years.

The pathologic material of the granulocytic sarcoma should be still available, to investigate if the sarcoma cells were Ph+ BCR-ABL+, and in that case if there was a BCR-ABL mutations.

If the pathologic material was analysed or can be analysed, and was Ph neg, BCR-ABL neg, I would suggest to continue the TKI, and to monitor very closely.

If the pathologic material was analysed or can be analysed, and was Ph+ BCR-ABL+, I would suggest to go to transplant. The risk of developing resistance would be very high.

If the pathologic material was not analysed and cannot be analysed, I would suggest to go to transplant as well, because morphology would not prove but would suggest that the granulocytic sarcoma was also Ph+ and BCR-ABL+.

Please, let me know the development.

34 female diagnosed CML May 2011, intermediate Sokal risk. Started on imatinib 400mg/d, obtained CCR at 3 months and MMR at 9 months.
In February 2013 bone fracture that was operated 3 times(!), the last in September 2013 when a local granulocytic sarcoma was found. At this time she was still in MMR and therefore a mutation analysis was not performed. She was treated with local radiotherapy (30Gy) and treatment was switched to Dasatinib 140mg/d.
At present she remains in MMR with good treatment tolerance. She has a compatible sibling, should we proceed to transplant?