Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia

Hagop M. Kantarjian, Susan O'Brien, Jorge Cortes, Francis J. Giles, Stefan Faderl, Jean Pierre Issa, Guillermo Garcia-Manero, Mary Beth Rios, Jianqin Shan, Michael Andreeff, Michael Keating, Moshe Talpaz

Research output: Contribution to journalArticle

Abstract

BACKGROUND. General and site-specific DNA methylation is associated with tumor progression and resistance in several cancers, including chronic myelogenous leukemia (CML). Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML. METHODS. One hundred and thirty patients with CML were treated: 123 with Philadelphia chromosome (Ph)-positive CML (64 blastic, 51 accelerated, 8 chronic) and 7 with Ph-negative CML. Decitabine was given at 100 mg/m2 over 6 hours every 12 hours × 5 days (1000 mg/m2 per course) in the first 13 patients, 75 mg/m2 in the subsequent 33 patients, and 50 mg/m2 in the remaining 84 patients. RESULTS. A total of 552 courses were given to the 130 patients. Only four patients (3%) died during the first course from myelosuppressive complications (three patients) or progressive disease (one patient). Of 64 patients in the CML blastic phase, 18 patients (28%) achieved objective responses. Of these 18 patients, 6 achieved complete hematologic responses (CHR), 2 achieved partial hematologic responses (PHR), 7 achieved hematologic improvements (HI), and 3 returned to the second chronic phase (second CP). Five patients (8%) had cytogenetic responses. Among 51 patients in the accelerated phase, 28 patients (55%) achieved objective responses (12 CHR, 10 PHR, 3 HI, and 3 second CP). Seven patients (14%) had cytogenetic responses. Among eight patients treated in the chronic phase, five (63%) had objective responses. Of seven patients treated for Ph-negative CML, four (57%) had objective responses. There was no evidence of a dose-response effect. The estimated 3-year survival rate was less than 5% in the blastic phase and 27% in the accelerated phase. The only significant toxicity reported was severe myelosuppression, which was delayed, prolonged, and dose dependent. With decitabine 50-75 mg/m2, the median time to granulocyte recovery above 0.5 × 109/L was about 4 weeks. Myelosuppression-associated complications included febrile episodes in 37% and documented infections in 34%. CONCLUSIONS. Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalCancer
Volume98
Issue number3
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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decitabine
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Therapeutics
Leukemia, Myeloid, Chronic Phase
Cytogenetics

Keywords

  • Chronic myelogenous leukemia
  • Decitabine
  • Myelosuppressive complications
  • Response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kantarjian, H. M., O'Brien, S., Cortes, J., Giles, F. J., Faderl, S., Issa, J. P., ... Talpaz, M. (2003). Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer, 98(3), 522-528. https://doi.org/10.1002/cncr.11543

Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. / Kantarjian, Hagop M.; O'Brien, Susan; Cortes, Jorge; Giles, Francis J.; Faderl, Stefan; Issa, Jean Pierre; Garcia-Manero, Guillermo; Rios, Mary Beth; Shan, Jianqin; Andreeff, Michael; Keating, Michael; Talpaz, Moshe.

In: Cancer, Vol. 98, No. 3, 01.08.2003, p. 522-528.

Research output: Contribution to journalArticle

Kantarjian, HM, O'Brien, S, Cortes, J, Giles, FJ, Faderl, S, Issa, JP, Garcia-Manero, G, Rios, MB, Shan, J, Andreeff, M, Keating, M & Talpaz, M 2003, 'Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia', Cancer, vol. 98, no. 3, pp. 522-528. https://doi.org/10.1002/cncr.11543
Kantarjian, Hagop M. ; O'Brien, Susan ; Cortes, Jorge ; Giles, Francis J. ; Faderl, Stefan ; Issa, Jean Pierre ; Garcia-Manero, Guillermo ; Rios, Mary Beth ; Shan, Jianqin ; Andreeff, Michael ; Keating, Michael ; Talpaz, Moshe. / Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. In: Cancer. 2003 ; Vol. 98, No. 3. pp. 522-528.
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abstract = "BACKGROUND. General and site-specific DNA methylation is associated with tumor progression and resistance in several cancers, including chronic myelogenous leukemia (CML). Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML. METHODS. One hundred and thirty patients with CML were treated: 123 with Philadelphia chromosome (Ph)-positive CML (64 blastic, 51 accelerated, 8 chronic) and 7 with Ph-negative CML. Decitabine was given at 100 mg/m2 over 6 hours every 12 hours × 5 days (1000 mg/m2 per course) in the first 13 patients, 75 mg/m2 in the subsequent 33 patients, and 50 mg/m2 in the remaining 84 patients. RESULTS. A total of 552 courses were given to the 130 patients. Only four patients (3{\%}) died during the first course from myelosuppressive complications (three patients) or progressive disease (one patient). Of 64 patients in the CML blastic phase, 18 patients (28{\%}) achieved objective responses. Of these 18 patients, 6 achieved complete hematologic responses (CHR), 2 achieved partial hematologic responses (PHR), 7 achieved hematologic improvements (HI), and 3 returned to the second chronic phase (second CP). Five patients (8{\%}) had cytogenetic responses. Among 51 patients in the accelerated phase, 28 patients (55{\%}) achieved objective responses (12 CHR, 10 PHR, 3 HI, and 3 second CP). Seven patients (14{\%}) had cytogenetic responses. Among eight patients treated in the chronic phase, five (63{\%}) had objective responses. Of seven patients treated for Ph-negative CML, four (57{\%}) had objective responses. There was no evidence of a dose-response effect. The estimated 3-year survival rate was less than 5{\%} in the blastic phase and 27{\%} in the accelerated phase. The only significant toxicity reported was severe myelosuppression, which was delayed, prolonged, and dose dependent. With decitabine 50-75 mg/m2, the median time to granulocyte recovery above 0.5 × 109/L was about 4 weeks. Myelosuppression-associated complications included febrile episodes in 37{\%} and documented infections in 34{\%}. CONCLUSIONS. Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases.",
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T1 - Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia

AU - Kantarjian, Hagop M.

AU - O'Brien, Susan

AU - Cortes, Jorge

AU - Giles, Francis J.

AU - Faderl, Stefan

AU - Issa, Jean Pierre

AU - Garcia-Manero, Guillermo

AU - Rios, Mary Beth

AU - Shan, Jianqin

AU - Andreeff, Michael

AU - Keating, Michael

AU - Talpaz, Moshe

PY - 2003/8/1

Y1 - 2003/8/1

N2 - BACKGROUND. General and site-specific DNA methylation is associated with tumor progression and resistance in several cancers, including chronic myelogenous leukemia (CML). Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML. METHODS. One hundred and thirty patients with CML were treated: 123 with Philadelphia chromosome (Ph)-positive CML (64 blastic, 51 accelerated, 8 chronic) and 7 with Ph-negative CML. Decitabine was given at 100 mg/m2 over 6 hours every 12 hours × 5 days (1000 mg/m2 per course) in the first 13 patients, 75 mg/m2 in the subsequent 33 patients, and 50 mg/m2 in the remaining 84 patients. RESULTS. A total of 552 courses were given to the 130 patients. Only four patients (3%) died during the first course from myelosuppressive complications (three patients) or progressive disease (one patient). Of 64 patients in the CML blastic phase, 18 patients (28%) achieved objective responses. Of these 18 patients, 6 achieved complete hematologic responses (CHR), 2 achieved partial hematologic responses (PHR), 7 achieved hematologic improvements (HI), and 3 returned to the second chronic phase (second CP). Five patients (8%) had cytogenetic responses. Among 51 patients in the accelerated phase, 28 patients (55%) achieved objective responses (12 CHR, 10 PHR, 3 HI, and 3 second CP). Seven patients (14%) had cytogenetic responses. Among eight patients treated in the chronic phase, five (63%) had objective responses. Of seven patients treated for Ph-negative CML, four (57%) had objective responses. There was no evidence of a dose-response effect. The estimated 3-year survival rate was less than 5% in the blastic phase and 27% in the accelerated phase. The only significant toxicity reported was severe myelosuppression, which was delayed, prolonged, and dose dependent. With decitabine 50-75 mg/m2, the median time to granulocyte recovery above 0.5 × 109/L was about 4 weeks. Myelosuppression-associated complications included febrile episodes in 37% and documented infections in 34%. CONCLUSIONS. Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases.

AB - BACKGROUND. General and site-specific DNA methylation is associated with tumor progression and resistance in several cancers, including chronic myelogenous leukemia (CML). Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML. METHODS. One hundred and thirty patients with CML were treated: 123 with Philadelphia chromosome (Ph)-positive CML (64 blastic, 51 accelerated, 8 chronic) and 7 with Ph-negative CML. Decitabine was given at 100 mg/m2 over 6 hours every 12 hours × 5 days (1000 mg/m2 per course) in the first 13 patients, 75 mg/m2 in the subsequent 33 patients, and 50 mg/m2 in the remaining 84 patients. RESULTS. A total of 552 courses were given to the 130 patients. Only four patients (3%) died during the first course from myelosuppressive complications (three patients) or progressive disease (one patient). Of 64 patients in the CML blastic phase, 18 patients (28%) achieved objective responses. Of these 18 patients, 6 achieved complete hematologic responses (CHR), 2 achieved partial hematologic responses (PHR), 7 achieved hematologic improvements (HI), and 3 returned to the second chronic phase (second CP). Five patients (8%) had cytogenetic responses. Among 51 patients in the accelerated phase, 28 patients (55%) achieved objective responses (12 CHR, 10 PHR, 3 HI, and 3 second CP). Seven patients (14%) had cytogenetic responses. Among eight patients treated in the chronic phase, five (63%) had objective responses. Of seven patients treated for Ph-negative CML, four (57%) had objective responses. There was no evidence of a dose-response effect. The estimated 3-year survival rate was less than 5% in the blastic phase and 27% in the accelerated phase. The only significant toxicity reported was severe myelosuppression, which was delayed, prolonged, and dose dependent. With decitabine 50-75 mg/m2, the median time to granulocyte recovery above 0.5 × 109/L was about 4 weeks. Myelosuppression-associated complications included febrile episodes in 37% and documented infections in 34%. CONCLUSIONS. Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases.

KW - Chronic myelogenous leukemia

KW - Decitabine

KW - Myelosuppressive complications

KW - Response

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