Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities

Farhad Ravandi, Jean Pierre Issa, Guillermo Garcia-Manero, Susan O'Brien, Sherry Pierce, Jianqin Shan, Gautam Borthakur, Srdan Verstovsek, Stefan Faderl, Jorge Cortes, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years. METHODS: The authors investigated whether treatment with hypomethylating agents (5-azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46%] with AML [≥20% blasts]; 44 [54%] with high-risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (≥3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine-based regimens in 72% and other regimes in 28%). RESULTS: The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37-85 years and 19-89 years). Thirty-three (41%) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35%) in the chemotherapy group (P = .395). With a median follow-up of 51 weeks (range, 12-101 weeks) and 40 weeks (range, 5-128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P = .153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P = .019). CONCLUSIONS: Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities.

Original languageEnglish (US)
Pages (from-to)5746-5751
Number of pages6
JournalCancer
Volume115
Issue number24
DOIs
StatePublished - Dec 15 2009
Externally publishedYes

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Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 7
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Drug Therapy
Therapeutics
decitabine
Azacitidine
Cytarabine
Age Groups
Recurrence
Survival

Keywords

  • 5-Azacytidine
  • Acute myeloid leukemia
  • Chemotherapy
  • Decitabine
  • High-risk myelodysplastic syndrome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities. / Ravandi, Farhad; Issa, Jean Pierre; Garcia-Manero, Guillermo; O'Brien, Susan; Pierce, Sherry; Shan, Jianqin; Borthakur, Gautam; Verstovsek, Srdan; Faderl, Stefan; Cortes, Jorge; Kantarjian, Hagop.

In: Cancer, Vol. 115, No. 24, 15.12.2009, p. 5746-5751.

Research output: Contribution to journalArticle

Ravandi, F, Issa, JP, Garcia-Manero, G, O'Brien, S, Pierce, S, Shan, J, Borthakur, G, Verstovsek, S, Faderl, S, Cortes, J & Kantarjian, H 2009, 'Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities', Cancer, vol. 115, no. 24, pp. 5746-5751. https://doi.org/10.1002/cncr.24661
Ravandi, Farhad ; Issa, Jean Pierre ; Garcia-Manero, Guillermo ; O'Brien, Susan ; Pierce, Sherry ; Shan, Jianqin ; Borthakur, Gautam ; Verstovsek, Srdan ; Faderl, Stefan ; Cortes, Jorge ; Kantarjian, Hagop. / Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities. In: Cancer. 2009 ; Vol. 115, No. 24. pp. 5746-5751.
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abstract = "BACKGROUND: Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10{\%} of patients alive at 2 years. METHODS: The authors investigated whether treatment with hypomethylating agents (5-azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46{\%}] with AML [≥20{\%} blasts]; 44 [54{\%}] with high-risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (≥3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine-based regimens in 72{\%} and other regimes in 28{\%}). RESULTS: The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37-85 years and 19-89 years). Thirty-three (41{\%}) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35{\%}) in the chemotherapy group (P = .395). With a median follow-up of 51 weeks (range, 12-101 weeks) and 40 weeks (range, 5-128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P = .153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P = .019). CONCLUSIONS: Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities.",
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T1 - Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities

AU - Ravandi, Farhad

AU - Issa, Jean Pierre

AU - Garcia-Manero, Guillermo

AU - O'Brien, Susan

AU - Pierce, Sherry

AU - Shan, Jianqin

AU - Borthakur, Gautam

AU - Verstovsek, Srdan

AU - Faderl, Stefan

AU - Cortes, Jorge

AU - Kantarjian, Hagop

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N2 - BACKGROUND: Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years. METHODS: The authors investigated whether treatment with hypomethylating agents (5-azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46%] with AML [≥20% blasts]; 44 [54%] with high-risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (≥3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine-based regimens in 72% and other regimes in 28%). RESULTS: The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37-85 years and 19-89 years). Thirty-three (41%) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35%) in the chemotherapy group (P = .395). With a median follow-up of 51 weeks (range, 12-101 weeks) and 40 weeks (range, 5-128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P = .153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P = .019). CONCLUSIONS: Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities.

AB - BACKGROUND: Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years. METHODS: The authors investigated whether treatment with hypomethylating agents (5-azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46%] with AML [≥20% blasts]; 44 [54%] with high-risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (≥3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine-based regimens in 72% and other regimes in 28%). RESULTS: The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37-85 years and 19-89 years). Thirty-three (41%) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35%) in the chemotherapy group (P = .395). With a median follow-up of 51 weeks (range, 12-101 weeks) and 40 weeks (range, 5-128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P = .153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P = .019). CONCLUSIONS: Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities.

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