Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine.

Abstract

Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts > 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P < 10(-4)) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P < 10(-4)). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P < 10(-4)). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.

• Authors: Raphael Itzykson, Sylvain Thépot, Bruno Quesnel, Francois Dreyfus, Odile Beyne-Rauzy, Pascal Turlure, Norbert Vey, Christian Recher, Caroline Dartigeas, Laurence Legros, Jacques Delaunay, Célia Salanoubat, Sorin Visanica, Aspasia Stamatoullas, Francoise Isnard, Anne Marfaing-Koka, Stephane de Botton, Youcef Chelghoum, Anne-Laure Taksin, Isabelle Plantier, Shanti Ame, Simone Boehrer, Claude Gardin, C L Beach, Lionel Adès, Pierre Fenaux, Groupe Francophone des Myelodysplasies(GFM)
• Journal: Blood (Blood) Vol. 117 Issue 2 Pg. 403-11 (Jan 13 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 20940414 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Azacitidine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (therapeutic use)
• Azacitidine (therapeutic use)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, mortality)
• Prognosis
• Young Adult