ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response

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 t...

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Bibliographic Details
Published in:American journal of clinical pathology 2002-03, Vol.117 (3), p.360-367
Main Authors: Hasserjian, Robert P, Boecklin, Federica, Parker, Sally, Chase, Andy, Dhar, Sunanda, Zaiac, Michael, Olavarria, Eduardo, Lampert, Irvin, Henry, Kristin, Apperley, Jane F, Goldman, John M
Format: Article
Language:English
Subjects:
Antineoplastic Agents - therapeutic use
Benzamides
Biopsy
Bone Marrow - pathology
Cell Count
Cell Differentiation
Cytogenetic Analysis
Fibrosis
Hematopoiesis
Hematopoietic Stem Cells - pathology
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
Megakaryocytes - pathology
Necrosis
Piperazines - therapeutic use
Pyrimidines - therapeutic use
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Summary: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 exhibitfeatures resembling normal hematopoiesis.
ISSN:0002-9173