Efficacy of ex vivo purging for autologous bone marrow transplantation in the treatment of acute nonlymphoblastic leukemia

S. D. Rowley, R. J. Jones, S. Piantadosi, H. G. Braine, O. M. Colvin, J. Davis, R. Saral, S. Sharkis, J. Wingard, A. M. Yeager, G. W. Santos

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4-hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 ± 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 ± 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of > 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a ≤ 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.

Original languageEnglish (US)
Pages (from-to)501-506
Number of pages6
JournalBlood
Volume74
Issue number1
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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