Evaluation of Cytopenias Occurring in Imatinib Treated Chronic Myeloid Leukemia (CML) Patients

Abstract

Imatinib Mesylate, a Tyrosine Kinase inhibitor, is presently the drug of choice for Chronic myeloid leukemia (CML). During therapy, a few patients develop myelosuppression and present with cytopenias. To study the bone marrow morphology in imatinib treated CML patients presenting with persistent cytopenias. The cases were retrieved from the Hematopathology record files, Department of Pathology; the study period being January 2008-June 2009. Cases of CML on Imatinib presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenias with bone marrow studies, were included in the study. The morphology of all cases was reviewed with cytogenetic studies. Follow-up details were obtained from the Medical Oncology records. During the study period, 683 Imatinib treated CML patients had bone marrow studies as part of their follow-up investigations. Of these, 60 patients (9%) had some form of persistent cytopenia. The patients ranged from 21 to 75 years of age with a median age of 38 years. The male:female ratio was 1:1. There were 46 patients with ≥grade 2 anemia, 25 patients with ≥grade 2 neutropenia and 37 patients with ≥grade 2 thrombocytopenia. Of these, 18 patients had bicytopenia and 13 cases had pancytopenia. The marrow evaluation revealed morphologic response in 30 patients, persistent marrow disease in five patients, marrow hypoplasia in six patients, extensive stromal changes including fibrosis in five patients, megaloblastic erythropoiesis in 11 patients and disease progression to accelerated or blast crisis in three patients. Various degrees of cytopenias may occur in few patients of CML on imatinib therapy. Regular hematologic follow-up is required so that the drug may be stopped or dose modified as per the individual's needs.

Various treatment responses in Imatinib treated CML patients with emphasis on marrow profile: a descriptive study in a tertiary care centre in South India

“…[2] There are very few studies from Indian subcontinent which correlates haematological, cytogenetic and marrow response after Imatinib treatment. [4,5,10] In this study, the marrow changes three months post Imatinib were correlated with HR and CR. Imatinib induces durable hematologic and cytogenetic responses in patients of CML, though the former is achieved earlier.…”

“…Varying degrees of cytopenias do occur in patients of CML on Imatinib, though most of them are transient and mild. [10] Though most of the patients have the classical Philadelphia chromosome, Philadelphia variants do occur in patients of CML. Imatinib is known to provide durable hematological responses in such patients too [14].…”

“…The marrow status at the end of 3 months were classified as follows [10] • Normalization of marrow: normalization of cellularity and M:E ratio (according to age), no increase in immature precursors/ blast, abnormal megakaryocytes less than 10%.…”

Gelatinous Marrow Transformation in an Imatinib-Treated CML Patient with Pancytopenia Following Severe Sepsis

“…GMT occurring in imatinib-treated CML is a relatively recently described phenomenon [5][6][7][8]. The precise mechanism remains obscure although drug-induced downregulation of transforming growth factor beta signal transduction resulting in reduced synthesis of normal extracellular matrix (ECM) as well as blockade of platelet derived growth factor receptor-mediated fibrosis have been implicated [5,6].…”

“…The precise mechanism remains obscure although drug-induced downregulation of transforming growth factor beta signal transduction resulting in reduced synthesis of normal extracellular matrix (ECM) as well as blockade of platelet derived growth factor receptor-mediated fibrosis have been implicated [5,6]. Only two of the five previously reported cases of GMT (summarized in Table 1) in association with CML had pancytopenia, one had bicytopenia and two had normal blood counts at the time of diagnosis of GMT [5][6][7][8]. None of the previous authors reported any co-morbidities unlike our patient who had recently emerged from a serious systemic infection and had a history of recurring visceral malignancy treated with chemotherapy.…”