Complete molecular response of e6a2 BCR-ABL–positive acute myeloid leukemia to imatinib then dasatinib

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2896-2898 ◽  
Author(s):  
David S. Ritchie ◽  
Michelle McBean ◽  
David A Westerman ◽  
Sergey Kovalenko ◽  
John F. Seymour ◽  
...  

De novo presentation of acute myeloid leukemia (AML) expressing the Philadelphia (Ph) chromosomal abnormality is rare and is associated with a dismal prognosis. To date, reported cases of Ph+ AML have expressed either the e13a2 or e14a2 BCR-ABL fusion transcripts. We report a unique case of de novo AML expressing the e6a2 fusion transcript and describe disease sensitivity to both imatinib before allogeneic stem-cell transplantation and dasatinib for AML relapse after allogeneic stem-cell transplantation. Furthermore, we report that sustained molecular remission has been achieved despite withdrawal of tyrosine kinase inhibitor (TKI) therapy.

Blood ◽  
2009 ◽  
Vol 113 (26) ◽  
pp. 6567-6571 ◽  
Author(s):  
Stephan Metzelder ◽  
Ying Wang ◽  
Ellen Wollmer ◽  
Michael Wanzel ◽  
Sabine Teichler ◽  
...  

Abstract Acute myeloid leukemia (AML) patients with internal tandem duplication (ITD) mutations in the Fms-like tyrosine-3 (FLT3) gene have a dismal prognosis. Here we report compassionate-use results with the multikinase and FLT3-ITD inhibitor sorafenib for the treatment of relapsed or refractory FLT3-ITD–positive AML. Sorafenib induced clinically meaningful and very rapid responses in all 6 patients treated either before (n = 2), after (n = 3), or both before and after (n = 1) allogeneic stem cell transplantation (allo-SCT). Sorafenib-induced remissions facilitated allo-SCT in 2 of the 3 refractory patients. Two of the 4 patients who were treated after allo-SCT survived 216 and 221 days, respectively, whereas the other 2 remain in ongoing complete molecular remission. Sorafenib response was associated with an inhibition of the antiapoptotic FLT3-ITD target Stat-5 in vivo. Together, sorafenib monotherapy before or after allo-SCT has remarkable clinical activity in poor risk FLT3-ITD–positive AML and deserves further evaluation in prospective clinical trials.


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