A Phase II Trial of Autologous Bone Marrow Transplantation (ABMT) in Acute Leukemia with Edelfosine Purged Bone Marrow

  • William R. Vogler
  • Wolfgang E. Berdel
  • Robert B. Geller
  • Joel A. Brochstein
  • Roy A. Beveridge
  • William S. Dalton
  • Kenneth B. Miller
  • Hillard M. Lazarus
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 416)


Alkyl-lysophospholipids are analogs of naturally occurring lyso-phospholipids initially synthesized as immunologic modifiers to render macrophages more cytocidal to tumor cells1. However, early experiments indicated that these compounds had direct anti-tumor activity 2. In addition, it was found that these compounds were selectively toxic to tumor cells and had less effect on normal cells3–5. The most active of these compounds was 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, formerly termed ET-18OCH3 and more recently named edelfosine. If indeed the compounds were selectively toxic to leukemic cells and spared normal cells, particularly normal bone marrow progenitor cells, they might prove effective in purging leukemic cells from remission marrows in patients with acute leukemia who were candidates for ABMT. Incubation of human leukemic cell lines and freshly obtained leukemic cells from patients demonstrated that the compounds were active whether measured by viability, tritiated thymidine incorporation or clonogenic assays 6–8. When a sensitive cell line (HL60) was mixed with normal marrow cells and incubated with varying doses of edelfosine for 1 to 4 hours it was found that a 4 hour incubation with 50 μg/ml eliminated clonogenic leukemic cells with no effect on normal marrow progenitor cells 9. In a murine leukemic model in which a remission marrow was simulated by mixing WEHI 3/b leukemic cells with normal murine marrow cells and exposing the mixture in vitro to edelfosine prior to injection intravenously into lethally irradiated littermates resulted in a dose responsive prolongation of survival with apparent cures 10. Similar results were obtained after freezing and thawing the mixture prior to injection11. Following these results a phase I clinical trial was initiated and the results have been published 12. It was found that a 4 hour incubation at a dose of 75 µ/ml was the optimal dose for purging. Based on these results a phase II trial was designed with participation by multiple institutions.


Complete Remission Leukemic Cell Acute Leukemia Peripheral Blood Stem Cell Autologous Bone Marrow Transplantation 
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  1. 1.
    Munder PG, Weltzien HU, Modolell M: Lysolecithin analogs: a new class of immunopotentiators. Immunodeficiency and immunostimulation, in Miescher PA (ed): Seventh international symposium on immunopathology, Basel/Stuttgard, Schwabe & Co, 1976, p 411Google Scholar
  2. 2.
    Munder PG, Modolell M, Bausert W, Oettgen HF, Westphal O: alkyllysophospholipids in cancer therapy, in Hersh EM (ed): Augmenting agents in cancer therapy, New York, Raven Press, 1981, p 441Google Scholar
  3. 3.
    Andreesen R, Modolell M, Weltzien HU, Eibl H, Common HH, Lohr GW, Munder PG: Selective destruction of human leukemic cells by alkyl-lysophospholipids. Cancer Res 38: 3894, 1978PubMedGoogle Scholar
  4. 4.
    Modelell M, Andreesen R, Pahlke W, Brugger U, Munder PG: Disturbance of phospholipid metabolism by the selective destruction of tumor cells by alkyl-lysophospholipids. Cancer Res 39: 4681, 1979Google Scholar
  5. 5.
    Andreesen R, Modollel M, Munder PG: Selective sensitivity of chronic myelogenous leukemic cell populations to alkyl-lysophospholipids. Blood 54: 519, 1979PubMedGoogle Scholar
  6. 6.
    Vogler WR, Whigham EA, Somberg LB, Long RC, Winton EF: The effect of alkyl-lysophospholipids on tritiated thymidine incorporation and clonogenicity in vitro of normal and leukemic human cells. Exp Hematol 12: 569, 1984PubMedGoogle Scholar
  7. 7.
    Verdonck LF, Witteveen EO, van Heugten HG, Rozemuller E, Rijksen G: Selective killing of malignant cells from leukemic patients by alkyl-lysophospholipid. Cancer Res 50: 4020, 1990PubMedGoogle Scholar
  8. 8.
    Dulisch I, Neumann HA, Lohr GW, Andreesen R: Clonogenicity of normal and malignant hematopoietic progenitor cells after exposure to alkyl-lysophospholipids. Blut 51: 393, 1985PubMedCrossRefGoogle Scholar
  9. 9.
    Okamoto S, Olson AC, Vogler WR, Winton EF: Purging leukemic cells from simulated remission marrow with alkyl-lysophospholipids. Blood 69: 1381, 1987PubMedGoogle Scholar
  10. 10.
    Glasser L, Somberg LB, Vogler WR: Purging murine leukemic marrow with alkyl-lysophospholipids. Blood 64: 1288, 1984PubMedGoogle Scholar
  11. 11.
    Vogler WR, Somberg LB, Glasser L: Effect of cryopreservation on purging of leukemic marrow with alkyllysophospholipids. Exp Hematol 15: 360, 1987PubMedGoogle Scholar
  12. 12.
    Vogler WR, Berdel WE, Olson AC, Winton EF, Heffner LT, Gordon DS: Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid. Blood 80: 1423, 1992PubMedGoogle Scholar
  13. 13.
    Gorin NC, Aegerter P, Auvert B, Meloni B, Goldstone AH, Burnett A, Carella A, Korbling M, Herve P, Maraninchi D, Lowenberg R, Verdonck LF, de Planque M, Hermans J, Helbig W, Porcellini A, Rizzoli V, Alesandrino EP, Franklin IM, Reiffers J, Colleselli P, Goldman JM: Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging. Blood 75: 1606, 1990PubMedGoogle Scholar
  14. 14.
    Laporte JP, Douay L, Lopez M, Labopin M, Jouet JP, Lesage S, Stachowiak L, Fouillard L, Isnard F, Noel-Walter MP, Pene F, Deloux J, Van Dan Akker J, Bauters F, Najman A, Gorin NC: One hundred twenty-five adult patients with primary acute leukemia autografted with marrow purged by mafosfamide: a 10-year single institution experience. Blood 84: 3810, 1994PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • William R. Vogler
    • 1
  • Wolfgang E. Berdel
    • 2
  • Robert B. Geller
    • 1
  • Joel A. Brochstein
    • 3
  • Roy A. Beveridge
    • 4
  • William S. Dalton
    • 5
  • Kenneth B. Miller
    • 6
  • Hillard M. Lazarus
    • 7
  1. 1.Emory UniversityAtlantaGeorgia
  2. 2.Freie UniverstätBerlinGermany
  3. 3.Hackensack Medical CenterHackensackUSA
  4. 4.Fairfax Hematology-Oncology AssociatesAnnadaleUSA
  5. 5.University of ArizonaTusconUSA
  6. 6.New England Medical Center Tufts University School of MedicineBostonUSA
  7. 7.Case Western Reserve UniversityClevelandUSA

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