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


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.


CONCLUSIONS
Long-term treatment with STI571 exerts pronounced changes on BM histopathology that not only involve haematopoiesis and stromal constituents, but also proliferation and apoptosis.
Thiele
J
J
Institutes of Pathology, University of Cologne, Germany. j.thiele@uni-koeln.de
Kvasnicka
H M
HM
Schmitt-Graeff
A
A
Kriener
S
S
Engels
K
K
Staib
P
P
Ollig
E S
ES
Keller
C
C
Fokkema
S
S
Griesshammer
M
M
Waller
C F
CF
Ottmann
O G
OG
Hansmann
M L
ML
D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D001706:Biopsy; D001854:Bone Marrow Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000032:analysis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D013997:Time Factors
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D039661:Integrin beta3; D010879:Piperazines; D018809:Proliferating Cell Nuclear Antigen; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases