Submitted October 17, 2008
Accepted March 7, 2009
Failure to achieve a complete hematologic response at the time of achievement of a major cytogenetic response with second generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase
Carmen Fava, Hagop M Kantarjian, Elias Jabbour, Susan O'Brien, Nitin Jain, Mary Beth Rios, Guillermo Garcia-Manero, Farhad Ravandi, Srdan Verstovsek, Gautam Borthakur, Jianqin Shan, and Jorge Cortes*
Department of Leukemia, MD Anderson Cancer Center, Houston, TX, United States
* Corresponding author; email: jcortes{at}mdanderson.org.
Second generation tyrosine kinase inhibitors are effective in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Occasionally, patients with Ph+ ALL or accelerated (AP) or blast-phase (BP) CML achieve a major cytogenetic response (MCyR) but not a complete hematologic response (CHR). We analyzed 126 patients with CML in AP (n=83) or BP (n=57), or Ph+ ALL (n=6) treated with dasatinib (53) or nilotinib (73) after imatinib failure. Twenty patients received sequential treatment with both dasatinib and nilotinib for a total of 146 instances. CHR and MCyR rates were 54% and 37%, respectively in AP, 17% and 39% in BP, and 33% and 50% in Ph+ ALL. Failure to achieve a CHR at the time of achievement of MCyR was associated with an inferior outcome similar to that of patients without MCyR (2-year survival 37% and 35%, respectively). In contrast, patients with MCyR and concomitant CHR had a 77% 2-year survival. Twelve of 29 patients with MCyR without concomitant CHR later achieved CHR; 2-year survival for these patients was 55% compared to 22% for those who never achieved a CHR. These results suggest that achievement of MCyR without a concomitant CHR is associated with a poor outcome.
