Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: A CALGB Intergroup Phase II Study

Brian I. Rini, Susan Halabi, Robert Barrier, Kim A. Margolin, David Avigan, Theodore Logan, Walter M. Stadler, Philip L. McCarthy, Charles A. Linker, Eric J. Small

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35 Scopus citations

Abstract

A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT. The conditioning regimen was fludarabine 30 mg · m-2 · d-1 on day (d) -7 through d -3 and cyclophosphamide 60 mg · kg-1 · d-1 on d -4 and d -3. Patients received 2-8 × 106 CD34+ cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120. No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach. Allogeneic SCT remains investigational in RCC.

Original languageEnglish (US)
Pages (from-to)778-785
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2006

Keywords

  • Allogeneic
  • Nonmyeloablative transplant
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Transplantation

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    Rini, B. I., Halabi, S., Barrier, R., Margolin, K. A., Avigan, D., Logan, T., Stadler, W. M., McCarthy, P. L., Linker, C. A., & Small, E. J. (2006). Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: A CALGB Intergroup Phase II Study. Biology of Blood and Marrow Transplantation, 12(7), 778-785. https://doi.org/10.1016/j.bbmt.2006.03.011