title: Long term outcome of Ph+ CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era.
abstract: Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty-seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow-up, the BCR-ABL transcripts level was available in 96/101 living patients (95%) The BCR-ABL:ABL ratio was between 0.1 and 0.01% (MR(3.0) ) in 17%, and less than 0.01% (MR(4.0) ) in 81% of patients. No patient was completely molecular negative (MR(4.5) or MR(5.0) ). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR(4.0) . Complete molecular response (MR(4.5) or MR(5.0) ) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα.
authors.affiliation: Chair of Haematology, Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, 25100, Brescia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Cristina
authors.initials: C
authors.lastname: Skert
authors.forename: Valeria
authors.initials: V
authors.lastname: Cancelli
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Federica
authors.initials: F
authors.lastname: Cattina
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Liberati
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.forename: Mario
authors.initials: M
authors.lastname: Annunziata
authors.forename: Elena
authors.initials: E
authors.lastname: Trabacchi
authors.forename: Antonio
authors.initials: A
authors.lastname: De Vivo
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Miriam
authors.initials: M
authors.lastname: Fogli
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.forename: Gianmatteo
authors.initials: G
authors.lastname: Pica
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pregno
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pardini
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.forename: Sabina
authors.initials: S
authors.lastname: Russo
authors.forename: Ivana
authors.initials: I
authors.lastname: Pierri
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.forename: Sara
authors.initials: S
authors.lastname: Barulli
authors.forename: Serena
authors.initials: S
authors.lastname: Merante
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Gianatonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl