Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion

Autor: Pierre Fenaux, Eric Wattel, Francis Bauters, Dominique Bordessoule, Jean-Loup Demory, Yvon Sterkers, Jean-Luc Laï, Claude Preudhomme, M. T. Caulier
Přispěvatelé: Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire d'Hématologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Virologie et pathogenèse virale (VPV), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service des Maladies du Sang, Hôpital Huriez, Groupe français des myéloplastes and groupe ouest est des leucemies aigües myéloïde (SERVICE DES MALADIES DU SANG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
Jazyk: angličtina
Rok vydání: 1998
Předmět:
Zdroj: Blood
Blood, American Society of Hematology, 1998, 91 (2), pp.616-22
ResearcherID
Europe PubMed Central
ISSN: 0006-4971
1528-0020
Popis: Treatment with alkylating agents or radiophosphorous (32P) has been shown to carry a certain leukemogenic risk in myeloproliferative disorders (MPDs), including essential thrombocytemia (ET). The leukemogenic risk associated to treatment with hydroxyurea in ET, on the other hand, is generally considered to be relatively low. Between 1970 and 1991, we diagnosed ET in 357 patients, who were monitored until 1996. One or several therapeutic agents had been admistered to 326 patients, including hydroxyurea (HU) in 251 (as only treatment in 201), pipobroman in 43, busulfan in 41, and32P in 40. With a median follow-up duration of 98 months, 17 patients (4.5%) had progressed to acute myeloid leukemia (AML; six cases) or myelodysplastic syndrome (MDS; 11 cases). Fourteen of these patients had received HU, as sole treatment in seven cases, and preceded or followed by other treatment in seven cases, mainly pipobroman (five cases). The remaining three leukemic progressions occurred in patients treated with 32P (two cases) and busulfan (one case). The incidence of AML and MDS after treatment, using 32P alone and 32P with other agents, busulfan alone and with other agents, HU alone and with others agents, and pipobroman alone and with other agents was 7% and 9%, 3% and 17%, 3.5% and 14%, and 0% and 16%, respectively. Thirteen of 17 patients who progressed to AML or MDS had successful cytogenetic analysis. Seven of them had rearrangements of chromosome 17 (unbalanced translocation, partial or complete deletion, isochromosome 17q) that resulted in 17p deletion. They also had a typical form of dysgranulopoiesis combining pseudo Pelger Hüet hypolobulation and vacuoles in neutrophils, and p53 mutation, as previously described in AML and MDS with 17p deletion. Those seven patients had all received HU, as the only therapeutic agent in three, and followed by pipobroman in three. The three patients who had received no HU and progressed to AML or MDS had no 17p deletion. A review of the literature found cytogenetic analysis in 35 cases of AML and MDS occurring after ET, 11 of whom had been treated with HU alone. Five of 35 patients had rearrangements that resulted in 17p deletion. Four of them had been treated with HU alone. These results show that treatment with HU alone is associated with a leukemic risk of approximately 3.5%. A high proportion of AML and MDS occurring in ET treated with HU (alone or possibly followed by pipobroman) have morphologic, cytogenetic, and molecular characteristics of the 17p− syndrome. These findings suggest that widespread and prolonged use of HU in ET may have to be reconsidered in some situations, such as asymptomatic ET.
Databáze: OpenAIRE
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