Interleukin-2-activated hematopoietic stem cell transplantation for breast cancer: Investigation of dose level with clinical correlates

K. R. Meehan, U. N. Verma, R. Cahill, S. Frankel, E. M. Areman, R. A. Sacher, R. Foelber, C. Rajagopal, E. A. Gehan, M. E. Lippman, A. Mazumder

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24 Scopus citations

Abstract

Incubating hematopoietic stem cells with IL-2 in vitro for 24 h generates cytotoxic T cells. When infused into patients, these cells may stimulate a graft-versus-tumor (GVT) effect. This clinical trial was designed to assess the ability of IL-2 activated peripheral blood stem cells (PBSC) to reconstitute hematopoiesis, to investigate dose levels and dose-limiting toxicities of IL-2, and to evaluate clinical results and preliminary laboratory effects using a combination of IL-2-activated autologous PBSC followed by IL-2 after transplantation. Sixty-one women with stage II-IV breast cancer were treated. After the administration of carboplatin (200 mg/m2/day for 3 days) and cyclophosphamide (2 g/m2/day for 3 days), patients received autologous PBSC that were cultured in IL-2 for 24 h followed by parenteral administration of IL-2 beginning the day of transplantation. Three escalating doses of IL-2 were evaluated with increasing duration up to 4 weeks. Of the 57 patients receiving IL-2 after tranplantation, 19 patients (33.3%) were unable to complete the planned course of IL-2 therapy due to persistent fevers (n = 9), diarrhea (n 2), pulmonary capillary leak syndrome (n = 3), development of a rash (n = 1), atrial fibrillation (n = 1), or patient's request (n = 3). One death occurred during hospitalization. Engraftment of neutrophils occurred on day 11.5 (mean; range 8-21 days) and platelets on day 11.7 (mean; range 7-33 days). The maximal tolerated dose of IL-2 was 6 x 105 IU/m2/day for 4 weeks. Disease-free survival rates for all stages were comparable to current reports in the literature. Preliminary laboratory evaluations include FACScan analysis of the IL-2 activated PBSC demonstrating an increased percentage of CD3+, CD25+, HLA-DR+ T cells. Phenotypically similar cells were present in peripheral blood samples of patients when tested 15 days after transplantation. This study demonstrates successful engraftment with IL-2-activated PBSC after high-dose chemotherapy for women with stage II-IV breast cancer. The regimen is feasible and, although toxicities are common, they are manageable and correlate with increasing dose and duration of IL-2.

Original languageEnglish (US)
Pages (from-to)643-651
Number of pages9
JournalBone Marrow Transplantation
Volume20
Issue number8
DOIs
StatePublished - Oct 2 1997

Keywords

  • Breast cancer
  • Immunotherapy
  • Interleukin-2
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Meehan, K. R., Verma, U. N., Cahill, R., Frankel, S., Areman, E. M., Sacher, R. A., Foelber, R., Rajagopal, C., Gehan, E. A., Lippman, M. E., & Mazumder, A. (1997). Interleukin-2-activated hematopoietic stem cell transplantation for breast cancer: Investigation of dose level with clinical correlates. Bone Marrow Transplantation, 20(8), 643-651. https://doi.org/10.1038/sj.bmt.1700954