Literature DB >> 18085610

Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: need for new response definitions?

Hagop Kantarjian1, Susan O'Brien, Jianqin Shan, Xuelin Huang, Guillermo Garcia-Manero, Stefan Faderl, Farhad Ravandi-Kashani, Srdan Verstovsek, Mary Beth Rios, Jorge Cortes.   

Abstract

BACKGROUND: Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy.
METHODS: In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment.
RESULTS: The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74% versus 62%, and of undetectable BCR-ABL transcripts 38% versus 24%. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]-positivity <or=35%) at 6 months to 12 months and survival as well as progression-free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for >or=12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71% of patients on imatinib therapy; undetectable BCR-ABL transcripts documented at least twice were noted in 34%.
CONCLUSIONS: Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments. Cancer 2008. (c) 2007 American Cancer Society.

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Year:  2008        PMID: 18085610     DOI: 10.1002/cncr.23238

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  40 in total

1.  Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION).

Authors:  Hagop M Kantarjian; Neil P Shah; Jorge E Cortes; Michele Baccarani; Mohan B Agarwal; María Soledad Undurraga; Jianxiang Wang; Juan Julio Kassack Ipiña; Dong-Wook Kim; Michinori Ogura; Carolina Pavlovsky; Christian Junghanss; Jorge H Milone; Franck E Nicolini; Tadeusz Robak; Jan Van Droogenbroeck; Edo Vellenga; M Brigid Bradley-Garelik; Chao Zhu; Andreas Hochhaus
Journal:  Blood       Date:  2011-12-09       Impact factor: 22.113

2.  Early prediction of a long-term outcome by neutrophil-FISH in patients with CML receiving imatinib mesylate.

Authors:  Naoto Takahashi; Yoshihiro Kameoka; Hiroyuki Tagawa; Hirobumi Saitoh; Tomoko Yoshioka; Naohito Fujishima; Atsushi Kitabayashi; Kaoru Takahashi; Makoto Hirokawa; Kenichi Sawada
Journal:  Int J Hematol       Date:  2010-09-14       Impact factor: 2.490

Review 3.  Molecular monitoring of BCR-ABL transcripts in patients with chronic myelogenous leukemia: is high sensitivity of clinical value?

Authors:  Maxim Norkin; Charles A Schiffer
Journal:  Curr Hematol Malig Rep       Date:  2010-04       Impact factor: 3.952

Review 4.  Molecular resistance: an early indicator for treatment change?

Authors:  Carmen Fava; Hagop Kantarjian; Jorge Cortes
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2012-01-28

5.  Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study.

Authors:  Michele Baccarani; Brian J Druker; Susan Branford; Dong-Wook Kim; Fabrizio Pane; Lidia Mongay; Manisha Mone; Christine-Elke Ortmann; Hagop M Kantarjian; Jerald P Radich; Timothy P Hughes; Jorge E Cortes; François Guilhot
Journal:  Int J Hematol       Date:  2014       Impact factor: 2.490

6.  Chronic myeloid leukemia 2011: successes, challenges, and strategies--proceedings of the 5th annual BCR-ABL1 positive and BCR-ABL1 negative myeloproliferative neoplasms workshop.

Authors:  Tariq I Mughal; Jerald P Radich; Richard A Van Etten; Alfonso Quintás-Cardama; Tomasz Skorski; Farhad Ravandi; Daniel J DeAngelo; Carlo Gambacorti-Passerini; Giovanni Martinelli; Ayalew Tefferi
Journal:  Am J Hematol       Date:  2011-09       Impact factor: 10.047

7.  Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS).

Authors:  Timothy P Hughes; Andreas Hochhaus; Susan Branford; Martin C Müller; Jaspal S Kaeda; Letizia Foroni; Brian J Druker; François Guilhot; Richard A Larson; Stephen G O'Brien; Marc S Rudoltz; Manisha Mone; Elisabeth Wehrle; Vijay Modur; John M Goldman; Jerald P Radich
Journal:  Blood       Date:  2010-08-02       Impact factor: 22.113

8.  Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission.

Authors:  Mariana Serpa; Sabri S Sanabani; Pedro Enrique Dorliac-Llacer; Monika Conchon; Thales Dalessandro Meneguin Pereira; Luciana Nardinelli; Juliana Lima Costa; Mafalda Megumi Yoshinaga Novaes; Patricia de Barros Ferreira; Israel Bendit
Journal:  BMC Blood Disord       Date:  2010-11-18

Review 9.  Tyrosine kinase inhibition: a therapeutic target for the management of chronic-phase chronic myeloid leukemia.

Authors:  Elias J Jabbour; Jorge E Cortes; Hagop M Kantarjian
Journal:  Expert Rev Anticancer Ther       Date:  2013-12       Impact factor: 4.512

10.  Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy.

Authors:  Gabriel Etienne; Stéphanie Dulucq; Franck-Emmanuel Nicolini; Stéphane Morisset; Marie-Pierre Fort; Anna Schmitt; Madeleine Etienne; Sandrine Hayette; Eric Lippert; Caroline Bureau; Isabelle Tigaud; Didier Adiko; Gérald Marit; Josy Reiffers; François-Xavier Mahon
Journal:  Haematologica       Date:  2013-12-20       Impact factor: 9.941

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