Bone marrow changes in chronic myelogenous leukaemia after long-term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients

• Published in: Histopathology Vol. 46; no. 5; pp. 540 - 550
• Main Authors: Thiele, J, Kvasnicka, H M, Schmitt-Graeff, 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
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2005; Blackwell
• Subjects: Antigens, CD34 - analysis; Antineoplastic Agents - therapeutic use; apoptosis; Benzamides; Biological and medical sciences; Biopsy; blasts; bone marrow; Bone Marrow Cells - chemistry; Bone Marrow Cells - drug effects; Bone Marrow Cells - pathology; Female; Hematologic and hematopoietic diseases; Humans; imatinib (STI571); Imatinib Mesylate; Immunohistochemistry; Integrin beta3 - analysis; Investigative techniques, diagnostic techniques (general aspects); Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; megakaryocytes; Middle Aged; myelofibrosis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Piperazines - therapeutic use; Proliferating Cell Nuclear Antigen - analysis; proliferation; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - therapeutic use; Time Factors; Immunohistochemistry; Cell proliferation; Megakaryocyte; Blast; Myeloproliferative syndrome; Chronic myelocytic leukemia; Bone marrow; Protein-tyrosine kinase; Human; blasts; Imatinib; Myelofibrosis; megakaryocytes; Enzyme; Transferases; Enzyme inhibitor; Patient; Malignant hemopathy; Proliferation; Long term; Anatomic pathology; Chronic; Treatment; Cell death; imatinib (STI571); Apoptosis
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2005.02119.x

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.