title: Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM).
abstract: Transformation of Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs) to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is associated with poor response to chemotherapy and short survival. Fifty-four patients with Ph-negative MPN (including 21 essential thrombocythemia [ET], 21 polycythemia vera [PV], 7 primary myelofibrosis, and 5 unclassified MPN) who had progressed to AML (n = 26) or MDS (n = 28) were treated with azacitidine in a patient-named program. Overall response rate was 52% (24% complete response [CR], 11% partial response [PR], 8% marrow CR or CR with incomplete recovery of cytopenias, 9% hematologic improvement) and median response duration was 9 months. Prognostic factors were for overall response the underlying MPN (71% vs 33% responses in ET and PV, respectively; P = .016); prognostic factors for CR achievement were the underlying MPN (14% CR for PV vs 43% for ET; P = .040) and World Health Organization classification at transformation (36% vs 12% CR in MDS and AML, respectively, P = .038). Recurrence of chronic phase features of the initial MPN was observed in 39% of the responders. Median overall survival was 11 months. Azacitidine gives encouraging results in Ph-negative MPN having progressed to AML or MDS, but response duration is short, and consolidation treatments have to be evaluated.
authors.affiliation: Service d'Hematologie Clinique, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Université Paris 13, Bobigny, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Thepot
authors.forename: Raphael
authors.initials: R
authors.lastname: Itzykson
authors.forename: Valerie
authors.initials: V
authors.lastname: Seegers
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesnel
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Chait
authors.forename: Lucile
authors.initials: L
authors.lastname: Sorin
authors.forename: Francois
authors.initials: F
authors.lastname: Dreyfus
authors.forename: Thomas
authors.initials: T
authors.lastname: Cluzeau
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.forename: Laurence
authors.initials: L
authors.lastname: Sanhes
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Caroline
authors.initials: C
authors.lastname: Dartigeas
authors.forename: Pascal
authors.initials: P
authors.lastname: Turlure
authors.forename: Stephanie
authors.initials: S
authors.lastname: Harel
authors.forename: Celia
authors.initials: C
authors.lastname: Salanoubat
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Lionel
authors.initials: L
authors.lastname: Adès
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics; D010677:Philadelphia Chromosome; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine