Faculty Collaboration Database

The alkyl-lysophospholipid, ET-18-OCH3 synergistically enhances the Merocyanine 540-mediated photoinactivation of leukemia cells: implications for the extracorporeal purging of autologous hematopoietic stem cells. Bone Marrow Transplant 1997 Jan;19(2):113-9

Date

01/02/1997

Pubmed ID

9116607

DOI

10.1038/sj.bmt.1700625

Scopus ID

2-s2.0-0031032095 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

Short-term exposure to the alkyl-lysophospholipid, rac-2-methyl-1-octadecyl-glycero-(3)-phosphocholine (ET-18-OCH3) or the photosensitizing dye, Merocyanine 540 (MC540) and light kills a wide range of leukemia and some solid tumor cells but is relatively well tolerated by normal pluripotent hematopoietic stem cells as well as certain classes of committed progenitor cells. Both ET-18-OCH3 and MC540-mediated photodynamic therapy (PDT) have been used as purging agents in preclinical models of autologous hematopoietic stem cell transplantation and are currently undergoing phase I/II clinical testing for the same purpose. We report here that ET-18-OCH3 synergistically enhances the MC540-mediated photoinactivation of leukemia cells but only minimally reduces the survival of normal granulocyte-macrophage progenitors. Therapeutic indices are most favorable when MC540-mediated PDT precedes incubation with ET-18-OCH3 and when purging is followed by cryopreservation. Taken together, these data suggest that combination purging with alkyl-lysophospholipid and MC540-mediated PDT may provide a simple, versatile, and effective means of eliminating large numbers of leukemia cells from autologous bone marrow grafts without causing excessive damage to normal hematopoietic stem cells.

Author List

Yamazaki T, Sieber F

Author

Fritz Sieber PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antineoplastic Agents
Blood Component Removal
Cell Death
Combined Modality Therapy
Drug Synergism
Hematopoietic Stem Cell Transplantation
Humans
Leukemia
Mice
Phospholipid Ethers
Photosensitizing Agents
Pyrimidinones
Tumor Cells, Cultured