Advertisement

Annals of Hematology

, 89:15 | Cite as

Comparison of various criteria in predicting treatment response and prognosis of patients with myelodysplastic syndrome treated with azacitidine

  • Dae-Young Kim
  • Je-Hwan LeeEmail author
  • Jung-Hee Lee
  • Kyoo-Hyung Lee
  • Yoe-Kyeoung Kim
  • Jae Sook Ahn
  • Hyeoung-Joon Kim
  • Inho Kim
  • Sung-Soo Yoon
  • Seonyang Park
  • Sung Hwa Bae
  • Soo-Mee BangEmail author
  • Hong Ghi Lee
  • Ho-Jin Shin
  • Jae Hoon Lee
  • Yoo Hong Min
  • Jong-Ho Won
  • Yeung-Chul Mun
  • Doyeun Oh
  • Korean Society of Hematology AML/MDS Working Party
Original Article

Abstract

This study was performed to identify whether cytogenetics, International Prognostic Scoring System (IPSS), or World Health Organization Classification-Based Prognostic Scoring System are predictive of the efficacy of azacitidine in patients with myelodysplastic syndrome (MDS). We retrospectively reviewed the clinical records of 113 patients with MDS treated with azacitidine. The “response alternating disease natural history,” “cytogenetic response,” and “hematologic improvement” were assessed by serial bone marrow biopsy, cytogenetic study, and hemogram analyses. The complete and partial remission rates were 17.6% and 3.9% in 51 evaluable patients. There were no significant differences in response rate in the different cytogenetic/IPSS/WPSS groups. The overall hematologic response (HR) rate was 49.6%, and the HR rate was significantly greater in patients classed as “very high” risk according to the WPSS compared with other patient groups. The 1-year overall survival (OS) rate was higher among patients with HR compared with those without HR (80.9% vs 63.3%, p = 0.046), and the 1-year OS rate among patients classed as being at high risk by each criteria was similar to that of patients classed as being at low risk. The hazard ratio of death among patients with HR compared with those without HR was 0.17 (95% CI 0.04–0.69) for high + very high risk group based on WPSS. Patients in the WPSS high-risk group had an increased HR rate compared with other patient groups, and the achievement of HR was associated with a significant increase in OS. Azacitidine showed similar efficacy in all patient groups, even in patients with poor cytogenetics and in high-risk groups.

Keywords

Azacitidine Cytogenetics IPSS WPSS 

Notes

Acknowledgments

We extend a special thanks to all members of the Korean AML/MDS Working Party. We particularly thank Byoung Kook Kim, Seong-Jun Choi, Hun-Mo Ryoo, and Mun Ju Jang for participation in this study.

Disclosures about potential conflict of interest

There is no relevant conflict of interest to declare for this study.

References

  1. 1.
    Silverman LR, Demakos EP, Peterson BL et al (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20:2429–2440CrossRefPubMedGoogle Scholar
  2. 2.
    Silverman LR, McKenzie DR, Peterson BL et al (2006) Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 24:3895–3903CrossRefPubMedGoogle Scholar
  3. 3.
    Plimack ER, Kantarjian HM, Issa JP (2007) Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma 48:1472–1481CrossRefPubMedGoogle Scholar
  4. 4.
    Kantarjian HM, O'Brien S, Huang X et al (2007) Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience. Cancer 109:1133–1137CrossRefPubMedGoogle Scholar
  5. 5.
    Leone G, Voso MT, Teofili L, Lubbert M (2003) Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol 109:89–102CrossRefPubMedGoogle Scholar
  6. 6.
    Oki Y, Issa JP (2007) Treatment options in advanced myelodysplastic syndrome, with emphasis on epigenetic therapy. Int J Hematol 86:306–314CrossRefPubMedGoogle Scholar
  7. 7.
    Lubbert M (2003) Gene silencing of the p15/INK4B cell-cycle inhibitor by hypermethylation: an early or later epigenetic alteration in myelodysplastic syndromes? Leukemia 17:1762–1764CrossRefPubMedGoogle Scholar
  8. 8.
    Raj K, John A, Ho A et al (2007) CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. Leukemia 21:1937–1944CrossRefPubMedGoogle Scholar
  9. 9.
    Daskalakis M, Nguyen TT, Nguyen C et al (2002) Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatment. Blood 100:2957–2964CrossRefPubMedGoogle Scholar
  10. 10.
    Gryn J, Zeigler ZR, Shadduck RK et al (2002) Treatment of myelodysplastic syndromes with 5-azacytidine. Leuk Res 26:893–897CrossRefPubMedGoogle Scholar
  11. 11.
    van den Bosch J, Lubbert M, Verhoef G, Wijermans PW (2004) The effects of 5-aza-2′-deoxycytidine (Decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes. Leuk Res 28:785–790CrossRefPubMedGoogle Scholar
  12. 12.
    Wijermans PW, Lubbert M, Verhoef G, Klimek V, Bosly A (2005) An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol 84(Suppl 1):9–17CrossRefPubMedGoogle Scholar
  13. 13.
    Lubbert M, Wijermans P, Kunzmann R et al (2001) Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol 114:349–357CrossRefPubMedGoogle Scholar
  14. 14.
    Greenberg P, Cox C, LeBeau MM et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088PubMedGoogle Scholar
  15. 15.
    Malcovati L, Germing U, Kuendgen A et al (2007) Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 25:3503–3510CrossRefPubMedGoogle Scholar
  16. 16.
    Cheson BD, Greenberg PL, Bennett JM et al (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108:419–425CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Dae-Young Kim
    • 1
  • Je-Hwan Lee
    • 1
    Email author
  • Jung-Hee Lee
    • 1
  • Kyoo-Hyung Lee
    • 1
  • Yoe-Kyeoung Kim
    • 2
  • Jae Sook Ahn
    • 2
  • Hyeoung-Joon Kim
    • 2
  • Inho Kim
    • 3
  • Sung-Soo Yoon
    • 3
  • Seonyang Park
    • 3
  • Sung Hwa Bae
    • 4
  • Soo-Mee Bang
    • 5
    Email author
  • Hong Ghi Lee
    • 6
  • Ho-Jin Shin
    • 7
  • Jae Hoon Lee
    • 8
  • Yoo Hong Min
    • 9
  • Jong-Ho Won
    • 10
  • Yeung-Chul Mun
    • 11
  • Doyeun Oh
    • 12
  • Korean Society of Hematology AML/MDS Working Party
  1. 1.Department of Hematology, Asan Medical CenterUniversity of Ulsan College of MedicineSongpa-guSouth Korea
  2. 2.Department of Internal Medicine, Chonnam National University Hwasun HospitalChonnam National University College of MedicineGwangjuKorea
  3. 3.Department of Internal Medicine, Seoul National University HospitalSeoul National University College of MedicineSeoulSouth Korea
  4. 4.Department of Internal Medicine, Daegu Catholic University Medical CenterDaegu Catholic University College of MedicineGyeongsanSouth Korea
  5. 5.Department of Internal Medicine, Seoul National University Bundang HospitalSeoul National University College of MedicineSeongnam-siSouth Korea
  6. 6.Department of Internal Medicine, Konkuk University Medical CenterKonkuk University College of MedicineSeoulSouth Korea
  7. 7.Department of Internal Medicine, Pusan National University HospitalPusan National University College of MedicinePusanSouth Korea
  8. 8.Department of Internal Medicine, Gachon University Gil Medical CenterGachon University of Medicine and ScienceIncheonSouth Korea
  9. 9.Department of Internal Medicine, Severance HospitalYonsei University College of MedicineSeoulSouth Korea
  10. 10.Department of Internal Medicine, Soon Chun Hyang University HospitalSoon Chun Hyang University College of MedicineSeoulSouth Korea
  11. 11.Department of Internal Medicine, Ewha Womans University Medical CenterEwha Womans University School of MedicineSeoulSouth Korea
  12. 12.Department of Internal Medicine, Bundang CHA HospitalPochon CHA University College of MedicineSeongnamSouth Korea

Personalised recommendations