title: Morphological effects of imatinib mesylate (STI571) on the bone marrow and blood of patients with Philadelphia chromosome (Ph) positive chronic myeloid leukaemia.
abstract: There have been few reports on the morphological findings in patients with chronic myeloid leukaemia (CML) undergoing treatment with imatinib mesylate. We examined morphological changes in the marrow and peripheral blood of 27 patients with chronic phase (CP), accelerated phase (AP) and blastic phase (BP) CML, 3 and 6 months after treatment with imatinib. At 3 months there was a significant clearance of leukaemic cells as evidenced by a complete haematological response (CHR) in the peripheral blood in 25 patients, together with reduced marrow cellularity in 25 (median reduction CP 42%; AP/BP 68%) and a reduction in the number of megakaryocytes (13 of 18 CP: five of six AP/BP; three patients did not have an assessable marrow) with an increase in the amount of normal megakaryopoiesis. After 6 months, there was continued morphological improvement in eight of 17 CP patients (one patient died after 3 months) with continued cytogenetic response (7 out of 15 patients with assessable metaphases had no abnormal Ph+ cells and three had <35% Ph+ cells) and maintenance of haematologic response in all patients. After an initial response to treatment at 3 months in the AP/BP group, with CHR and a reduction in cellularity in all patients, we found morphological evidence of a loss of response to treatment, with an increase in leukaemic cells, as evidenced by loss of CHR in three of nine and an increase in median cellularity in five patients. No patient in this group achieved a complete cytogenetic response. In summary, in CML-CP patients treated with 6 months of imatinib, there was a significant reduction in leukaemic cells as evidenced by a haematolological response in the peripheral blood, together with reduced marrow cellularity, restoration of morphologically normal haemopoiesis and a meaningful cytogenetic response. Maintaining a response to treatment appeared less likely to occur in the AP/BP group patients, especially those who did not achieve any cytogenetic response to treatment.
authors.affiliation: Department of Diagnostic Haematology, Royal Melbourne Hospital, Melbourne, VIC, Australia. chris.mcnamara@mh.org.au
authors.forename: C
authors.initials: C
authors.lastname: McNamara
authors.forename: A
authors.initials: A
authors.lastname: Grigg
authors.forename: J
authors.initials: J
authors.lastname: Szer
authors.forename: A
authors.initials: A
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Campbell
authors.forename: R
authors.initials: R
authors.lastname: Hoyt
authors.forename: K
authors.initials: K
authors.lastname: Lynch
authors.forename: S
authors.initials: S
authors.lastname: Juneja
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D002452:Cell Count; D020732:Cytogenetic Analysis; D004351:Drug Resistance; D005500:Follow-Up Studies; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012155:Reticulin / Q000097:blood; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D012155:Reticulin; D000068877:Imatinib Mesylate