Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe

Abstract

Patients with metastatic RCC, less than three metastatic locations and a Karnofsky score >70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD improved the patient survival.

Haploidentical hematopoietic SCT increases graft-versus-tumor effect against renal cell carcinoma

“…3,5,7 Addressing a strategy to control disease early after allogeneic HSCT might improve the survival of the patients with RCC. Haploidentical-SCT (haplo-SCT) could provide an enhanced allogeneic T-cell and natural killer (NK)-cell response and augment GVT effect due to the MHC molecule disparity.…”

“…In a European study, OS was found to be 30% at 2 years after HSCT. 3 However, CALGB data did not support these observations and did not report any objective responses after allogeneic HSCT in patients with advanced RCC. 6 Finally, in a recent report, Bregni and co-workers 7 observed a 5-year survival rate for 20% of 25 patients with metastatic RCC who had reduced intensity conditioning for allogeneic HSCT from HLA-compatible sibling donors.…”

“…However, pioneering studies suggest that non-myeloablative allogeneic HSCT for advanced renal cell cancer (RCC) might induce sustained regression of metastatic RCC in patients who have failed conventional therapies. [1][2][3][4][5] Seventy-four patients with advanced RCC underwent allogeneic HSCT following non-myeloablative conditioning, and 39% of the patients were responsive, including 9.5% of patients that underwent a CR. 5 The median tumor response occurred at 133 days after allogeneic HSCT and there were detectable RCC-reactive CD8 T-cells in responsive patients.…”

Is allogeneic transplant for solid tumors still alive?

“…2 After anecdotal reports in breast and lung cancer, Childs et al 3 reported in 2000 a consistent GVT effect of allogeneic stem cell transplant against renal cell cancer. GVT effect was then investigated in other tumors: As STWP of the EBMT, we completed several studies of allografting in selected solid tumors, namely renal cell cancer, 4 ovarian cancer, 5 breast cancer, 6 colorectal cancer 7 and others, with circumstantial evidence of GVT in some tumors and occurrence of transplant-related toxicities, mostly GvHD. In renal cell cancer, we have shown a long-term survival effect in a fraction (20%) of patients.…”

Combining allografting with mTOR inhibitors for metastatic renal cell cancer

“…In 2008 we initiated an IRB-approved prospective, single-arm phase II study (nicknamed AlloTOR), which combines a reduced-intensity conditioning, HLA-identical sibling donor allograft with post transplant temsirolimus for patients with advanced renal cell carcinoma (RCC) who have failed a thyrosine kinase inhibitor-based therapy. The clinical rationale of this approach relies on the long-term results of allograft in metastatic RCC, [2][3][4] and on the encouraging results of second-or third-line temsirolimus in patients resistant/ refractory to thyrosine kinase inhibitor therapy. 5 In addition, data suggest that rapamycin and related agents relatively increase Tregs and may be beneficial to the protection of the host without compromising the antitumor activity of the transplant.…”