bl-4162a and Myelodysplastic-Syndromes

Myeloproliferative disorders (MPDs) are chronic conditions that require long-term treatment. MPDs have been considered neoplastic disorders that have a propensity to transform to acute leukemia or myelodysplastic syndrome. One of the MPDs, chronic myeloid leukemia (CML), has the distinct cytogenetic abnormality of the Philadelphia chromosome. In CML, transformation to acute leukemia is a common occurrence, with the timeline measured in years rather than decades. With the other three disorders from this group, polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF), transformation to acute leukemia is less frequently seen and, although variable, can take a longer period of time. The choice of therapy used for MPDs may contribute to leukemic transformation; chlorambucil, busulfan, and radiophosphorus are all examples of therapy that have been shown to be leukemogenic. Several studies have suggested the potential leukemogenicity of hydroxyurea (HU), but this remains controversial because no randomized studies have been conducted. The two newest agents used for MPDs, interferon-alpha and anagrelide, have both been studied for efficacy, but their influence on the potential for leukemic transformation has not been well studied to date.

Topics: Antineoplastic Agents, Alkylating; Busulfan; Chlorambucil; Hydroxyurea; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Myeloproliferative Disorders; Philadelphia Chromosome; Platelet Aggregation Inhibitors; Quinazolines; Radiopharmaceuticals

A comparative immunohistochemical and morphometric study was performed on megakaryocytes in 20 patients presenting with initial-early stage chronic idiopathic myelofibrosis and accompanying thrombocythemia to elucidate histological features developing after hydroxyurea (HU) versus anagrelide (ANA) therapy. Representative pre-and posttreatment bone marrow biopsies were involved including the monoclonal antibody CD61 for the identification of precursor and mature stages of megakaryopoiesis. An elaborate morphometric evaluation was in keeping with a left-shifting showing a more frequent occurrence of promegakaryoblasts and microforms in both therapy groups. However, contrasting ANA, HU generated defects of differentiation consistent with significant dysplastic changes. In conclusion, concern about a possible leukemogenic capacity following long-term HU therapy is supported by our findings.

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Humans; Hydroxyurea; Immunohistochemistry; Megakaryocytes; Myelodysplastic Syndromes; Quinazolines; Retrospective Studies; Thrombopoiesis