Yin Xu1, Andrea E Wahner, Phuong L Nguyen. 1. Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, Minneapolis, USA. yin.xu@utsouthwestern.edu
Abstract
CONTEXT: Previous investigators have reported discrepancies between hematologic, marrow morphologic, and cytogenetic responses to imatinib mesylate among patients with chronic myeloid leukemia (CML). In addition to disease refractoriness, rare instances of disease progression from chronic phase to blast crisis during imatinib therapy have recently been anecdotally reported. OBJECTIVES: To describe the clinicopathologic features of 3 patients with CML who rapidly progressed from chronic phase to blast crisis while taking imatinib and to perform a review of the literature. DESIGN: Morphologic, immunophenotypic, and cytogenetic analyses were performed on the 3 patients at the time of initial diagnosis, during imatinib therapy, and at blast crisis. RESULTS: The 3 patients were men, aged 39, 42, and 43 years. Two had been treated with hydroxyurea for 16 and 21 months before imatinib therapy, while 1 was started on a regimen of imatinib following diagnosis. Despite a hematologic response in all 3 patients, none of them achieved cytogenetic remission, and all progressed to blast crisis at 7 to 10 months of imatinib therapy. Blood findings during blast transformation were heterogeneous, including normal blood morphologic findings in 1 patient, leukocytosis with circulating blasts and basophilia in 1, and marked pancytopenia in 1. All 3 marrow specimens demonstrated moderate to marked diffuse reticulin fibrosis with more than 20% blasts. Clonal cytogenetic evolution was evident in 2 of the 3 patients and included an extra Philadelphia chromosome in both. All 3 patients underwent allogeneic bone marrow transplantation. One was alive with no evidence of disease at 14 month follow-up, while 2 had residual disease after bone marrow transplantation and died of complications at 4 and 5 months after transplantation. CONCLUSIONS: Blood data did not always reflect marrow status. Therefore, bone marrow follow-up is critical for monitoring of response. Our findings suggest that significant progression of marrow reticulin fibrosis during imatinib therapy can be an indicator for a return or progression of CML and, in some patients with CML, imatinib may promote cytogenetic clonal evolution, resulting in a poor response to treatment.
CONTEXT: Previous investigators have reported discrepancies between hematologic, marrow morphologic, and cytogenetic responses to imatinib mesylate among patients with chronic myeloid leukemia (CML). In addition to disease refractoriness, rare instances of disease progression from chronic phase to blast crisis during imatinib therapy have recently been anecdotally reported. OBJECTIVES: To describe the clinicopathologic features of 3 patients with CML who rapidly progressed from chronic phase to blast crisis while taking imatinib and to perform a review of the literature. DESIGN: Morphologic, immunophenotypic, and cytogenetic analyses were performed on the 3 patients at the time of initial diagnosis, during imatinib therapy, and at blast crisis. RESULTS: The 3 patients were men, aged 39, 42, and 43 years. Two had been treated with hydroxyurea for 16 and 21 months before imatinib therapy, while 1 was started on a regimen of imatinib following diagnosis. Despite a hematologic response in all 3 patients, none of them achieved cytogenetic remission, and all progressed to blast crisis at 7 to 10 months of imatinib therapy. Blood findings during blast transformation were heterogeneous, including normal blood morphologic findings in 1 patient, leukocytosis with circulating blasts and basophilia in 1, and marked pancytopenia in 1. All 3 marrow specimens demonstrated moderate to marked diffuse reticulin fibrosis with more than 20% blasts. Clonal cytogenetic evolution was evident in 2 of the 3 patients and included an extra Philadelphia chromosome in both. All 3 patients underwent allogeneic bone marrow transplantation. One was alive with no evidence of disease at 14 month follow-up, while 2 had residual disease after bone marrow transplantation and died of complications at 4 and 5 months after transplantation. CONCLUSIONS: Blood data did not always reflect marrow status. Therefore, bone marrow follow-up is critical for monitoring of response. Our findings suggest that significant progression of marrow reticulin fibrosis during imatinib therapy can be an indicator for a return or progression of CML and, in some patients with CML, imatinib may promote cytogenetic clonal evolution, resulting in a poor response to treatment.
Authors: Mohammad Azam; Valentina Nardi; William C Shakespeare; Chester A Metcalf; Regine S Bohacek; Yihan Wang; Raji Sundaramoorthi; Piotr Sliz; Darren R Veach; William G Bornmann; Bayard Clarkson; David C Dalgarno; Tomi K Sawyer; George Q Daley Journal: Proc Natl Acad Sci U S A Date: 2006-06-05 Impact factor: 11.205