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Annals of Oncology Advance Access published online on June 21, 2006
Annals of Oncology, doi:10.1093/annonc/mdl129
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© 2006 European Society for Medical Oncology
Received March 31, 2006
Accepted April 28, 2006

review

Extramedullary disease and targeted therapies for hematological malignancies--is the association real?

P. Raanani 1 *, O. Shpilberg 1, and I. Ben-Bassat 2

1 Institute of Hematology, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
2 Institute of Hematology, The Chaim Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

* To whom correspondence should be addressed.
P. Raanani, E-mail: praanani{at}012.net.il


  Abstract

During the past years targeted therapies have gained a major role in the treatment of cancer patients, including those with hematological malignancies. Extramedullary involvement is a rare manifestation of acute and chronic leukemias and of multiple myeloma. Nevertheless, with the expanding use of targeted treatments there is an impression that the incidence of extramedullary relapses is increasing. We reviewed the reports on this phenomenon in patients treated with all-trans-retinoic acid and arsenic trioxide for acute promyelocytic leukemia, thalidomide and bortezomib for multiple myeloma and imatinib for chronic myeloid leukemia. The pathogenetic mechanisms suggested are: life prolongation by these treatments allowing for disease progression arising from dormant cells; poor penetration of the drugs to sanctuary sites like the central nervous system; the requirement of some of these drugs, especially thalidomide, for the marrow microenvironment to exert their action; and finally, a possible active role for some of the drugs, like all-trans-retinoic acid. Since the use of these targeted therapies is expanding we should be aware of this association.

Keywords: extramedullary; targeted therapy; ATRA; thalidomide; imatinib.
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