title: Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: a CALGB intergroup phase II study.
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 x 10(6) 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.
authors.affiliation: Department of Medicine, University of California San Francisco Cancer Center, San Francisco, California, USA. rinib2@ccf.org
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Robert
authors.initials: R
authors.lastname: Barrier
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: David
authors.initials: D
authors.lastname: Avigan
authors.forename: Theodore
authors.initials: T
authors.lastname: Logan
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Philip L
authors.initials: PL
authors.lastname: McCarthy
authors.forename: Charles A
authors.initials: CA
authors.lastname: Linker
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000556:secondary* / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D020350:Graft vs Tumor Effect / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007680:Kidney Neoplasms; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000379:methods*; D016019:Survival Analysis