Evaluation of in vivo antineoplastic effects of rapamycin in patients with chemotherapy-refractory AML

Boehm, Alexandra; Mayerhofer, Matthias; Herndlhofer, Susanne; Knoebl, Paul; Sillaber, Christian; Sperr, Wolfgang R.; Jaeger, Ulrich; Valent, Peter

doi:10.1016/j.ejim.2009.09.007

« Previous Next »European Journal of Internal Medicine
Volume 20, Issue 8 , Pages 775-778, December 2009

Evaluation of in vivo antineoplastic effects of rapamycin in patients with chemotherapy-refractory AML☆

Alexandra Boehm
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
- Bone Marrow Transplantation Unit, Medical University of Vienna, Austria
Matthias Mayerhofer
- Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria
Susanne Herndlhofer
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
Paul Knoebl
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
Christian Sillaber
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
Wolfgang R. Sperr
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
- Ludwig Boltzmann Cluster Oncology, Vienna, Austria
Ulrich Jaeger
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
- Ludwig Boltzmann Cluster Oncology, Vienna, Austria
Peter Valent
- Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria
- Ludwig Boltzmann Cluster Oncology, Vienna, Austria
- Corresponding author. Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, Ludwig Boltzmann Cluster Oncology, Vienna, A-1090 Vienna, Austria. Tel.: +43 1 40400 4415; fax: +43 1 40400 4030.

Received 14 July 2009; received in revised form 6 September 2009; accepted 8 September 2009. published online 08 October 2009.

Abstract

Background

The mammalian target of rapamycin (mTOR) has recently been identified as a potential target in acute myeloid leukemia (AML).

Methods

We treated 5 patients with chemotherapy-refractory AML with the mTOR-inhibitor rapamycin at 2mg per os daily for 14days, with dose adjustment allowed to reach a target serum rapamycin concentration of 10–20ng/mL. Four of five patients received additional hydroxyurea at constant dose during treatment with rapamycin.

Results

Two patients achieved a leukocyte response, in one of them, a prolonged response was seen. In the other patients, blast counts remained stable or increased during rapamycin therapy. We did not observe severe hematologic or non-hematologic side effects of rapamycin.

Conclusion

Rapamycin at 2mg per day acts mildly cytoreductive in a subgroup of patients with refractory AML. Higher doses and drug combinations may be required to obtain long lasting anti-leukemic effects in these patients.

Keywords: AML, Chemotherapy resistance, Rapamycin, mTOR