Autologous Peripheral Blood Stem Cell Transplantation and Adoptive Imniunotherapy with Activated Natural Killer Cells in the Immediate Posttransplant Period

John Lister, Witold Rybka, Albert D. Donnenberg, Margarida De Magalhaes-Silverman, Steven M. Pincus, Elana J. Bloom, Elaine M. Eider, Edward D. Ball, Theresa L. Whiteside

Research output: Contribution to journalArticle

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Abstract

Relapse after high-dose chemotherapy supported by peripheral blood stem cell transplantation (HDC-PBSCT) is the main cause of therapeutic failure in patients with lymphoma and breast cancer. Adoptive immunotherapy with activated natural killer (A-NK) cells and interleukin 2 might eliminate surviving residual tumor without adding to toxicity. Eleven patients with relapsed lymphoma and one with metastatic breast cancer were entered on a pilot clinical trial of HDC-PBSCT followed on day 2 after transplant by infusion of cultured autologous A-NK cells. Simultaneously, recombinant human interleukin 2 (rhIL-2) was initiated as a 4-day continuous i.v. infusion at 2 x 106 IU/m2/day, referred to as high-dose rhIL-2. Therapy with high-dose rhIL-2 was followed by a 90-day continuous i.v. infusion at 3 x 105 IU/m2/day, referred to as low-dose rhIL-2. All patients en- grafted and nine completed treatment. Posttransplant days to a neutrophil count of 500/μl and to a platelet count of 50,000/μl were similar to comparable patients treated with HDC-PBSCT alone. Generation of A-NK cells for therapy was feasible in all patients except the three patients with Hodgkin’s disease, whose cells did not proliferate in culture. Overall toxicity associated with early posttransplant transfer of A-NK cells and interleukin 2 did not differ from that observed with peripheral blood stem cell transplantation alone in comparable patients. There was early amplification of natural killer cell activity in the peripheral blood of four patients that appeared to result from the transfused A-NK cells. Adoptive transfer of A-NK cells and rhIL-2 during the pancytopenic phase after HDC-PBSCT was feasible and well tolerated, did not adversely affect engraftment, and resulted in amplified natural killer activity in the peripheral blood during the immediate posttransplantation period.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalClinical Cancer Research
Volume1
Issue number6
StatePublished - Jun 1 1995

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Peripheral Blood Stem Cell Transplantation
Natural Killer Cells
Interleukin-2
Drug Therapy
Lymphoma
Breast Neoplasms
Adoptive Immunotherapy
Adoptive Transfer
Residual Neoplasm
Cell- and Tissue-Based Therapy
Hodgkin Disease
Platelet Count
Neutrophils
Therapeutics
Clinical Trials
Transplants
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lister, J., Rybka, W., Donnenberg, A. D., Magalhaes-Silverman, M. D., Pincus, S. M., Bloom, E. J., ... Whiteside, T. L. (1995). Autologous Peripheral Blood Stem Cell Transplantation and Adoptive Imniunotherapy with Activated Natural Killer Cells in the Immediate Posttransplant Period. Clinical Cancer Research, 1(6), 607-614.
Lister, John ; Rybka, Witold ; Donnenberg, Albert D. ; Magalhaes-Silverman, Margarida De ; Pincus, Steven M. ; Bloom, Elana J. ; Eider, Elaine M. ; Ball, Edward D. ; Whiteside, Theresa L. / Autologous Peripheral Blood Stem Cell Transplantation and Adoptive Imniunotherapy with Activated Natural Killer Cells in the Immediate Posttransplant Period. In: Clinical Cancer Research. 1995 ; Vol. 1, No. 6. pp. 607-614.
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abstract = "Relapse after high-dose chemotherapy supported by peripheral blood stem cell transplantation (HDC-PBSCT) is the main cause of therapeutic failure in patients with lymphoma and breast cancer. Adoptive immunotherapy with activated natural killer (A-NK) cells and interleukin 2 might eliminate surviving residual tumor without adding to toxicity. Eleven patients with relapsed lymphoma and one with metastatic breast cancer were entered on a pilot clinical trial of HDC-PBSCT followed on day 2 after transplant by infusion of cultured autologous A-NK cells. Simultaneously, recombinant human interleukin 2 (rhIL-2) was initiated as a 4-day continuous i.v. infusion at 2 x 106 IU/m2/day, referred to as high-dose rhIL-2. Therapy with high-dose rhIL-2 was followed by a 90-day continuous i.v. infusion at 3 x 105 IU/m2/day, referred to as low-dose rhIL-2. All patients en- grafted and nine completed treatment. Posttransplant days to a neutrophil count of 500/μl and to a platelet count of 50,000/μl were similar to comparable patients treated with HDC-PBSCT alone. Generation of A-NK cells for therapy was feasible in all patients except the three patients with Hodgkin’s disease, whose cells did not proliferate in culture. Overall toxicity associated with early posttransplant transfer of A-NK cells and interleukin 2 did not differ from that observed with peripheral blood stem cell transplantation alone in comparable patients. There was early amplification of natural killer cell activity in the peripheral blood of four patients that appeared to result from the transfused A-NK cells. Adoptive transfer of A-NK cells and rhIL-2 during the pancytopenic phase after HDC-PBSCT was feasible and well tolerated, did not adversely affect engraftment, and resulted in amplified natural killer activity in the peripheral blood during the immediate posttransplantation period.",
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Lister, J, Rybka, W, Donnenberg, AD, Magalhaes-Silverman, MD, Pincus, SM, Bloom, EJ, Eider, EM, Ball, ED & Whiteside, TL 1995, 'Autologous Peripheral Blood Stem Cell Transplantation and Adoptive Imniunotherapy with Activated Natural Killer Cells in the Immediate Posttransplant Period', Clinical Cancer Research, vol. 1, no. 6, pp. 607-614.

Autologous Peripheral Blood Stem Cell Transplantation and Adoptive Imniunotherapy with Activated Natural Killer Cells in the Immediate Posttransplant Period. / Lister, John; Rybka, Witold; Donnenberg, Albert D.; Magalhaes-Silverman, Margarida De; Pincus, Steven M.; Bloom, Elana J.; Eider, Elaine M.; Ball, Edward D.; Whiteside, Theresa L.

In: Clinical Cancer Research, Vol. 1, No. 6, 01.06.1995, p. 607-614.

Research output: Contribution to journalArticle

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AU - Rybka, Witold

AU - Donnenberg, Albert D.

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AU - Whiteside, Theresa L.

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