Tyrosine kinase inhibitor STI571 in the treatment of Philadelphia chromosome-positive leukaemia failing myeloablative stem cell transplantation

Abstract

Summary:Eight patients with Philadelphia chromosome-positive (Ph + ) leukaemia relapsing from stem cell transplantation (SCT) (one syngeneic and seven allogeneic) were treated with the tyrosine kinase inhibitor STI571. Five patients relapsing as chronic myeloid leukaemia (CML) in chronic phase achieved a complete haematological response, with complete and major cytogenetic responses occurring in four and one cases, respectively. One patient became negative for BCR/ABL in the bone marrow. Three patients relapsed as acute leukaemia (two CML in myeloblastic crisis and one Ph + acute lymphoblastic leukaemia), all of whom achieved haematological and cytogenetic responses. One patient also became BCR/ABL negative. However, pancytopenia and graft-versus-host disease led to cessation of treatment in the remaining two cases, which was followed by disease recurrence refractory to further STI treatment. Our results showed that Ph + leukaemic relapses after SCT might respond well to STI571 therapy.

The Role of Imatinib in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

“…Potential responses to imatinib are possible post transplant relapse, however complications from SCT as well as refractory disease limit the use in this setting. 25 Second generation tyrosine kinase inhibitors demonstrate activity, but limited data exists, with the majority represented as case reports. Dasatinib therapy commencing after expression of imatinib resistance post stem cell transplant produced continuous reduction in BCR-ABL transcripts, with sustained remission reported 18 months post transplant.…”