Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: a CALGB intergroup phase II study.
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.
Rini
Brian I
BI
Department of Medicine, University of California San Francisco Cancer Center, San Francisco, California, USA. rinib2@ccf.org
Halabi
Susan
S
Barrier
Robert
R
Margolin
Kim A
KA
Avigan
David
D
Logan
Theodore
T
Stadler
Walter M
WM
McCarthy
Philip L
PL
Linker
Charles A
CA
Small
Eric J
EJ
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