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Bone marrow changes in chronic myelogenous leukaemia after long‐term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients
Author(s) -
Thiele J,
Kvasnicka H M,
SchmittGraeff A,
Kriener S,
Engels K,
Staib P,
Ollig E S,
Keller C,
Fokkema S,
Griesshammer M,
Waller C F,
Ottmann O G,
Hansmann M L
Publication year - 2005
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2005.02119.x
Subject(s) - bone marrow , granulopoiesis , myelofibrosis , chronic myelogenous leukemia , immunohistochemistry , pathology , medicine , haematopoiesis , imatinib mesylate , stromal cell , immunology , leukemia , biology , stem cell , imatinib , myeloid leukemia , genetics
Aims: To carry out an immunohistochemical study on bone marrow (BM) biopsy specimens in 75 patients with chronic myelogenous leukaemia (CML) on long‐term STI571 therapy. Methods and results: Sequential BM specimens taken at intervals of 21 ± 6 months were investigated by enzyme‐ and immunohistochemistry including proliferating cell nuclear antigen and apoptosis. Evaluation was performed either by semiquantitative scoring or by morphometry (CD61+ megakaryopoiesis). In 41 patients with chronic phase CML, treatment resulted in a significant decrease in cellularity and neutrophil granulopoiesis contrasting with an accumulation of erythroid precursor cells. Morphometry showed a reduction of abnormal micromegakaryocytes consistent with normalization. Regression of myelofibrosis was identified in eight of 15 patients, whereas progression occurred in 17 patients; mostly in those with acceleration and blastic crisis. The increased post‐treatment incidence of reactive lymphoid nodules was remarkable. Myeloblasts, CD34+ progenitors and immature myelomonocytic cells initially decreased, but recurred in 14 patients who later developed a relapse. STI571 exerted an inhibitory effect on cell proliferation associated with enhanced apoptosis in responding patients. Conclusion: Long‐term treatment with STI571 exerts pronounced changes on BM histopathology that not only involve haematopoiesis and stromal constituents, but also proliferation and apoptosis.