Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex

J. M. Rowe*, A. P. Rapoport, D. H. Ryan, B. I. Nilsson, R. E. Duerst, C. H. Packman, C. N. Abboud, J. F. Dipersio, T. Linder, N. Wang, B. Simonsson, J. L. Liesveld

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Unmanipulated autologous bone marrow transplant (ABMT) offers patients with chronic myelogenous leukemia (CML) a long-term survival of 10%, at best. Immunotherapy has a role in the myeloid leukemias, and there is increasing evidence that of all hematopoietic neoplasms, CML may be the most susceptible to immune regulation. Roquinimex is known to enhance T cell, NK cell and macrophage activity. A phase II study was initiated in March 1992 to evaluate the role of roquinimex in Ph chromosome-positive CML post ABMT. Patients were conditioned with busulfan/cyclophosphamide followed by reinfusion of unmanipulated Ph-positive bone marrow stem cells (> 1 x 108 NBC/kg). When engraftment of neutrophils (ANC) reached 100/μl, patients received oral roquinimex twice weekly, escalating to a maximal dose of 0.2 mg/kg in 2 weeks. Seventeen patients have entered the study; 11 in first chronic phase (CP1); two in second chronic phase (CP2) and four in accelerated phase (AP). All required significant myelosuppressive therapy prior to ABMT to maintain stable blood counts and most had also received prior interferon therapy. All patients survived the transplant. Subsequent toxicity consisted mainly of musculoskeletal aches and peripheral edema. Additionally, specific skin changes were observed including graft-versus-host-like disease and eccrine sweat gland necrosis. Eight out of 17 patients are alive 28-60 months post ABMT. Of the nine patients who died, two were in CP2 and three in AP. All patients in CP1 went into a complete hematological remission post ABMT and seven of the 11 patients had at least a major cytogenetic response (greater than 65% Ph-negative metaphases) at 1 year or beyond and four of the 11 patients had a complete cytogenetic response at 2 years or beyond. Cytogenetic response post transplant often developed over time and did not simply represent post ABMT engraftment with Ph-negative cells. The clinical and cytogenetic data in these patients are encouraging and suggest that roquinimex may have significant activity when given post ABMT to patients with Ph-positive CML.

Original languageEnglish (US)
Pages (from-to)1057-1063
Number of pages7
JournalBone Marrow Transplantation
Volume24
Issue number10
DOIs
StatePublished - Jan 1 1999

Keywords

  • Autotransplantation
  • Chronic myelogenous leukemia
  • Roquinimex

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Rowe, J. M., Rapoport, A. P., Ryan, D. H., Nilsson, B. I., Duerst, R. E., Packman, C. H., Abboud, C. N., Dipersio, J. F., Linder, T., Wang, N., Simonsson, B., & Liesveld, J. L. (1999). Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex. Bone Marrow Transplantation, 24(10), 1057-1063. https://doi.org/10.1038/sj.bmt.1702037