Philadelphia chromosome-negative engraftment after autologous transplantation with granulocyte-macrophage colony-stimulating factor for chronic myeloid leukemia

Douglas E. Gladstone, Atul Bedi, Carole B. Miller, Stephen J. Noga, Constance A. Griffin, Steven Piantadosi, Pablo J. Cagnoni, Robert A. Brodsky, B. Douglas Smith, Tracy T. Douglas, Elizabeth J. Shpall, Richard J. Jones

Research output: Contribution to journalArticle

Abstract

Autologous bone marrow transplantation (BMT) has not been curative in chronic myeloid leukemia (CML), because of the inability to purge CML from the autograft and the absence of the allogeneic T cell-mediated antileukemic activity. However, recent advances demonstrate that normal progenitors can be selected from CML marrows by a variety of techniques, including isolation by their small size. Furthermore, we found that myeloid growth factors have a potent antileukemic effect against CML progenitors in vitro by inducing their terminal differentiation. Based on these data, we initiated a trial of autologous BMT in patients with high-risk CML. Autografts were processed in an attempt to enrich for normal progenitors, first by isolating small cells by counterflow centrifugal elutriation and then incubating them in granulocyte-macrophage colony-stimulating factor (GM-CSF) for 72 hours. After a conditioning regimen of busulfan and cyclophosphamide, all patients received GM-CSF daily for 2 months. The median age of the 13 patients in the trial was 45 years (range 17-56 years). The median duration of disease before BMT was 24 months (range 13-72 months). Eight patients were in chronic phase (CP), and five were in accelerated phase (AP). All patients failed to achieve a cytogenetic response to interferon-α and were 100% Philadelphia chromosome (Ph)+ before BMT. There were three transplant-related deaths, all AP patients. All of the remaining 10 patients engrafted with some degree of Ph- hematopoiesis; despite high-risk features, nine patients engrafted 100% Ph-. All patients relapsed cytogenetically at a median of 6 months (range 4-22 months). These results demonstrate that autologous BMT can consistently induce complete Ph- engraftment in CP patients. GM-CSF appears to produce a clinical antileukemic effect against CML after autologous BMT.

Original languageEnglish (US)
Pages (from-to)394-399
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume5
Issue number6
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Autologous bone marrow transplantation
  • Chronic myeloid leukemia
  • Granulocyte-macrophage colony-stimulating factor

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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