Patients newly diagnosed with chronic phase chronic myeloid leukemia undergo treatment with
TK inhibitors (TKI). A possible cause of TK failure is represented by the insufficient
recovery of normal Ph- hematopoiesis during TKI treatment, with consequent severe cytopenias
that limit TKI adequate administration. Although rare, this event happens in a proportion of
4-5% of CML patients. Our hypothesis is to circumvent this peculiar condition by providing a
normal hematopoiesis from a HLA-matched donor (Human Leukocyte Antigen). The transplant
procedure is therefore intended in providing a sustained hematopoiesis that will allow an
early treatment with an adequate dosing of TKI. The transplant procedure planned in our study
is built on all available evidences to provide the lowest incidence of acute and chronic GvHD
(Graft-versus-host disease). Therefore, a bone marrow will be the preferential source and a
GvHD prophylaxis based on Anti-thrombocyte globulin (ATG) and Cyclosporine/Methotrexate will
be used according to standard current experience in the field of family and unrelated donors.
The pre-transplant TKI will be continued until aplasia will develop, in order to decrease the
tumor load as much as possible.The use of TKIs shortly after transplant carries the risk of
inhibiting the newly transplanted hematopoietic cells, as Kit, an important kinase in normal
bone marrow cells, is frequently blocked by Abl inhibitors. The use of bosutinib as
post-transplant therapy is justified by the lack of Kit inhibition that distinguishes
bosutinib from all other TKIs, and which could allow a minimal inhibitory activity against
the transplanted normal bone marrow.