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A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse.

Publication ,  Journal Article
Advani, AS; Shadman, M; Ali-Osman, F; Barker, A; Rybicki, L; Kalaycio, M; Sekeres, MA; de Castro, CM; Diehl, LF; Moore, JO; Beaven, A ...
Published in: Clin Lymphoma Myeloma Leuk
December 2010

INTRODUCTION: We evaluated the complete remission (CR) rate in patients with acute myeloid leukemia (AML) in first relapse treated with fixed-dose-rate gemcitabine and mitoxantrone. In addition, we measured multidrug resistance (MDR) proteins on pretreatment bone marrows and correlated expression with outcome. PATIENTS AND METHODS: The study was performed in a 2-stage design. Pretreatment bone marrows were assayed for the MDR proteins (LRP, MDR1, MRP1, SLC28-29A1/A2, ABCC4/C5, and GSTP1) by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Only 5 of the first 24 patients (21%) achieved CR; therefore, the study was terminated. Eleven patients (46%) had poor-risk cytogenetics and the median duration of first CR was 7.3 months. Patients had significant expression of the various MDR genes, with 70% of patients expressing moderate to high levels of GSTP1 by immunohistochemistry. Higher sum total of ABCC4 and SLC29A2 expression measured by RT-PCR was associated with not achieving CR (20.6 vs. 12.1; P = .006). In addition, there was a trend for higher expression of the sum total of the 10 MDR genes (measured by RT-PCR) and not achieving CR (P = .06). CONCLUSION: The CR rate in this study was comparable to other regimens used in poor-risk patients. Of interest, ABCC4 and SLC29A2 expression were predictive of achieving CR. The high expression of GSTP1 suggests that this may be a therapeutic target for relapsed AML. Finally, the rapidity and ease of using RT-PCR to quantify MDR in this study may have clinical utility in future trials.

Duke Scholars

Published In

Clin Lymphoma Myeloma Leuk

DOI

EISSN

2152-2669

Publication Date

December 2010

Volume

10

Issue

6

Start / End Page

473 / 476

Location

United States

Related Subject Headings

  • U937 Cells
  • Survival Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Remission Induction
  • Recurrence
  • Multidrug Resistance-Associated Proteins
  • Mitoxantrone
  • Middle Aged
  • Male
  • Leukemia, Myeloid
 

Citation

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Advani, A. S., Shadman, M., Ali-Osman, F., Barker, A., Rybicki, L., Kalaycio, M., … Rizzieri, D. A. (2010). A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse. Clin Lymphoma Myeloma Leuk, 10(6), 473–476. https://doi.org/10.3816/CLML.2010.n.082
Advani, Anjali S., Mazyar Shadman, Francis Ali-Osman, Andrew Barker, Lisa Rybicki, Matt Kalaycio, Mikkael A. Sekeres, et al. “A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse.Clin Lymphoma Myeloma Leuk 10, no. 6 (December 2010): 473–76. https://doi.org/10.3816/CLML.2010.n.082.
Advani AS, Shadman M, Ali-Osman F, Barker A, Rybicki L, Kalaycio M, et al. A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse. Clin Lymphoma Myeloma Leuk. 2010 Dec;10(6):473–6.
Advani, Anjali S., et al. “A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse.Clin Lymphoma Myeloma Leuk, vol. 10, no. 6, Dec. 2010, pp. 473–76. Pubmed, doi:10.3816/CLML.2010.n.082.
Advani AS, Shadman M, Ali-Osman F, Barker A, Rybicki L, Kalaycio M, Sekeres MA, de Castro CM, Diehl LF, Moore JO, Beaven A, Copelan E, Sobecks R, Talea P, Rizzieri DA. A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse. Clin Lymphoma Myeloma Leuk. 2010 Dec;10(6):473–476.
Journal cover image

Published In

Clin Lymphoma Myeloma Leuk

DOI

EISSN

2152-2669

Publication Date

December 2010

Volume

10

Issue

6

Start / End Page

473 / 476

Location

United States

Related Subject Headings

  • U937 Cells
  • Survival Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Remission Induction
  • Recurrence
  • Multidrug Resistance-Associated Proteins
  • Mitoxantrone
  • Middle Aged
  • Male
  • Leukemia, Myeloid