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STI571 (Imatinib Mesylate) Reduces Bone Marrow Cellularity and Normalizes Morphologic Features Irrespective of Cytogenetic Response

Robert P. Hasserjian MD, Federica Boecklin MD, Sally Parker, Andy Chase PhD, Sunanda Dhar MD, Michael Zaiac MD, Eduardo Olavarria MD, Irvin Lampert MBChB, Kristin Henry MD, Jane F. Apperley MD, John M. Goldman MD
DOI: http://dx.doi.org/10.1309/NR81-VCU0-CKW1-4HT9 360-367 First published online: 1 March 2002

Abstract

The tyrosine kinase inhibitor STI571 (imatinib mesylate, Gleevec) is an effective treatment for chronic myeloid leukemia (CML). We examined bone marrow samples from 53 patients with CML who were receiving STI571 in 3 multicenter phase 2 trials to assess morphologic changes and cytogenetic response to this drug. In most patients with initially increased blasts, the bone marrow blast count rapidly decreased during STI571 therapy. Reductions in cellularity, the myeloid/erythroid ratio (commonly with relative erythroid hyperplasia), and reticulin fibrosis (if present pretreatment) also were seen in most patients, resulting in an appearance resembling normal marrow in many cases. Eighteen patients (34%) had some degree of cytogenetic response. Surprisingly, these striking morphologic changes occurred irrespective of any cytogenetic response to STI571. Thus, STI571 seems to affect the differentiation of CML cells in vivo, causing even extensively Philadelphia chromosome–positive hematopoiesis to exhibit features resembling normal hematopoiesis.

Key Words:
  • STI571
  • Imatinib mesylate
  • Gleevec
  • CML
  • Therapy
  • Pathology
  • Bone marrow
  • Cytogenetics