“FLAG” Regimen Induces Deep, Although Short-Term, Responses in Patients Resistant to Tyrosine Kinases Inhibitors in BP CML.

Background:

Currently the main potential treatment for chronic myeloid leukemia (CML) blast phase (BP) are tyrosine kinase inhibitors. The aim of our study is to try to find any therapy in TKI resistant patients in CML BP.

Material and methods:

The patients were 5 male and one female (age range from 28 to 45 years old). 4 patients progressed to BP from chronic phase (CP), there was rapid progression from AP in other two pts (4 lymphoid, 1 myeloid, 1 undifferentiated). The pts were unresponsible to one or two second generation TKI treatment in BP (dasatinid, nilotinib). Two patients were also failed to respond to high dose cytarabine and methotrexate treatment after TKI failure. Chemotherapy «FLAG» (fludarabine, cytarabine high dose, G-CSF) was used to induce of CP.

Results:

Five of six pts achieved the second CP and deep response (1- CcyR, 3- MMR, and one BCR/ABL reduction to 0,371%).Two of these pts obtained deep response (CCyR, and bcr/abl reduction to 0.371% after unsuccessful treatment with dose mono cytarabine and methotrexat treatment. The response was short, the longest MMR duration is 48 days (patient is being prepared for ASCT).

Conclusion:

FLAG can induce deep molecular responses in BP pts resistant to TKIs. This regimen seems to be more effective than HDAC and HD MTX. The response is of short duration. Thus, in case of absence of relative sibling, haploidentical ASCT with unmanipulated bone marrow and posttransplantation cyclophosphamide could be the optimal treatment choice. The protocol for FLAG induced remission followed haploidentical ASCT is prepared.