Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype

A cancer and leukemia group B study

Sherif Farag, Amy S. Ruppert, Krzysztof Mrózek, Robert J. Mayer, Richard M. Stone, Andrew J. Carroll, Bayard L. Powell, Joseph O. Moore, Mark J. Pettenati, Prasad R K Koduru, Judith Stamberg, Maria R. Baer, Annemarie W. Block, James W. Vardiman, Jonathan E. Kolitz, Charles A. Schiffer, Richard A. Larson, Clara D. Bloomfield

Research output: Contribution to journalArticle

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Abstract

Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML). Patients and Methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV). Results: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P <.001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis. Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.

Original languageEnglish (US)
Pages (from-to)482-493
Number of pages12
JournalJournal of Clinical Oncology
Volume23
Issue number3
DOIs
StatePublished - 2005
Externally publishedYes

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Etoposide
Daunorubicin
Karyotype
Acute Myeloid Leukemia
Cytarabine
Young Adult
Leukemia
Disease-Free Survival
Neoplasms
diaziquone
Recurrence
Cytogenetics
Therapeutics
Mitoxantrone
Splenomegaly
Incidence
Stem Cell Transplantation
Cyclophosphamide
Survival Rate
Transplantation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype : A cancer and leukemia group B study. / Farag, Sherif; Ruppert, Amy S.; Mrózek, Krzysztof; Mayer, Robert J.; Stone, Richard M.; Carroll, Andrew J.; Powell, Bayard L.; Moore, Joseph O.; Pettenati, Mark J.; Koduru, Prasad R K; Stamberg, Judith; Baer, Maria R.; Block, Annemarie W.; Vardiman, James W.; Kolitz, Jonathan E.; Schiffer, Charles A.; Larson, Richard A.; Bloomfield, Clara D.

In: Journal of Clinical Oncology, Vol. 23, No. 3, 2005, p. 482-493.

Research output: Contribution to journalArticle

Farag, S, Ruppert, AS, Mrózek, K, Mayer, RJ, Stone, RM, Carroll, AJ, Powell, BL, Moore, JO, Pettenati, MJ, Koduru, PRK, Stamberg, J, Baer, MR, Block, AW, Vardiman, JW, Kolitz, JE, Schiffer, CA, Larson, RA & Bloomfield, CD 2005, 'Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: A cancer and leukemia group B study', Journal of Clinical Oncology, vol. 23, no. 3, pp. 482-493. https://doi.org/10.1200/JCO.2005.06.090
Farag, Sherif ; Ruppert, Amy S. ; Mrózek, Krzysztof ; Mayer, Robert J. ; Stone, Richard M. ; Carroll, Andrew J. ; Powell, Bayard L. ; Moore, Joseph O. ; Pettenati, Mark J. ; Koduru, Prasad R K ; Stamberg, Judith ; Baer, Maria R. ; Block, Annemarie W. ; Vardiman, James W. ; Kolitz, Jonathan E. ; Schiffer, Charles A. ; Larson, Richard A. ; Bloomfield, Clara D. / Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype : A cancer and leukemia group B study. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 3. pp. 482-493.
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abstract = "Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML). Patients and Methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV). Results: Of 350 patients receiving AD, 73{\%} achieved complete remission (CR), compared with 82{\%} of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P <.001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28{\%} each for intensification groups I and II, compared with 41{\%} and 45{\%} for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62{\%} and 67{\%} for groups I and II, respectively, compared with 54{\%} and 44{\%} for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis. Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.",
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T1 - Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype

T2 - A cancer and leukemia group B study

AU - Farag, Sherif

AU - Ruppert, Amy S.

AU - Mrózek, Krzysztof

AU - Mayer, Robert J.

AU - Stone, Richard M.

AU - Carroll, Andrew J.

AU - Powell, Bayard L.

AU - Moore, Joseph O.

AU - Pettenati, Mark J.

AU - Koduru, Prasad R K

AU - Stamberg, Judith

AU - Baer, Maria R.

AU - Block, Annemarie W.

AU - Vardiman, James W.

AU - Kolitz, Jonathan E.

AU - Schiffer, Charles A.

AU - Larson, Richard A.

AU - Bloomfield, Clara D.

PY - 2005

Y1 - 2005

N2 - Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML). Patients and Methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV). Results: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P <.001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis. Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.

AB - Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML). Patients and Methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV). Results: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P <.001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis. Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.

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