Allison Kemner

Publications (2)10.38 Total impact

• Article: A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia.

  Donald E Tsai, Selina M Luger, Charalambos Andreadis, Dan T Vogl, Allison Kemner, Melissa Potuzak, Ami Goradia, Alison W Loren, Alexander E Perl, Stephen J Schuster, David L Porter, Edward A Stadtmauer, Steven C Goldstein, James E Thompson, Cezary Swider, Adam Bagg, Anthony R Mato, Martin Carroll
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  ABSTRACT: Bexarotene is a retinoic X receptor agonist that has been shown in vitro to inhibit growth and induce differentiation of myeloid leukemic cell lines. We therefore conducted a phase I dose escalation study to assess the maximum tolerated dose, toxicities, and activity of bexarotene in patients with non-M3 acute myeloid leukemia (AML). We enrolled patients with active non-M3 AML who had either relapsed or refractory disease or were not eligible for standard cytotoxic chemotherapy. Cohorts of three to six patients received escalating doses of daily oral bexarotene ranging from 100 to 400 mg/m(2) until evidence of disease progression or unacceptable adverse events occurred. Twenty-seven patients, with median age of 69 years (range, 51-82 years), were treated. Twenty-four (89%) patients had undergone prior chemotherapy. At the highest dose level tested (400 mg/m(2)), three of six patients had to reduce their dose of bexarotene due to grade 3 adverse events. The maximum tolerable dose of bexarotene was determined to be 300 mg/m(2). Clinical activity was manifested by 4 (15%) patients with reduction in bone marrow blasts to <or=5%, 11 (41%) patients with improved platelet counts, and 7 (26%) patients with improved neutrophil counts. Three patients with relapsed AML survived >1 year while taking bexarotene. Leukemic blast differentiation was suggested by the presence of the leukemic cytogenetic abnormality in mature circulating granulocytes and the occurrence of differentiation syndrome. The recommended dose of bexarotene for future studies is 300 mg/m(2)/d. Bexarotene is well tolerated in patients with non-M3 AML and has evidence of antileukemic activity.
  Clinical Cancer Research 09/2008; 14(17):5619-25. · 7.74 Impact Factor
• Source

  Available from: Cezary Swider

  Article: Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene.

  Donald E Tsai, Selina M Luger, Allison Kemner, Cezary Swider, Ami Goradia, Ewa Tomczak, Doris DiPatri, Adam Bagg, Peter Nowell, Alison W Loren, Alexander Perl, Stephen Schuster, James E Thompson, David Porter, Charlambos Andreadis, Edward A Stadtmauer, Steven Goldsteini, Richard Ghalie, Martin Carroll
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  ABSTRACT: All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML. We report on two patients with relapsed or refractory non-M3 AML treated with bexarotene monotherapy. After initiating treatment, both patients showed leukemic differentiation in their peripheral blood and reduction in bone marrow blasts to less than 5%. One patient had a significant improvement in her platelet count with loss of platelet transfusion needs. Differentiation syndrome occurred in one patient and was successfully treated with steroids and discontinuation of bexarotene. These data suggest that bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid differentiation in vivo.
  Cancer biology & therapy 02/2007; 6(1):18-21. · 2.64 Impact Factor