Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience

Abstract

Summary:Nonmyeloablative allogeneic stem cell transplantation (NST) has considerable activity in patients with metastatic renal cell carcinoma (RCC), although there are limited long-term follow-up data. Between February 1999 and May 2003, 18 patients with metastatic RCC underwent 19 matched-sibling NSTs after conditioning with fludarabine and cyclophosphamide with tacrolimus and mycophenolate mofetil as posttransplant immunosuppression. Among the four objective responses, all were partial and have relapsed with a median response duration of 609 days (range, 107-926). All responders are alive at a median of 41 months. Median overall survival for the entire cohort was 14 months. There were four early treatment-related deaths and one late treatment-related death. Eight patients died from progressive disease and five (28%) from treatment-related mortality. Stratifying transplant outcome as early death, intermediate (no response, no early death), or response, the combination of pre-treatment anemia and decreased performance status, was associated with adverse outcome (P ¼ 0.015) and reduced survival (HR 5.4, 95% confidence interval of 1.4 to 21, P ¼ 0.007). Responders demonstrated prolonged survival compared to nonresponders (P ¼ 0.002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification.

Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings

“…Nevertheless, both interferon alpha and IL-2 are toxic, and the large majority of individuals who receive them derive no benefit. Efforts to develop more sophisticated immunotherapy platforms for this disease, including newer cytokine therapy (Alatrash et al, 2004), vaccine therapy (Uemura et al, 2006;Ernstoff et al, 2007), and nonmyeloablative transplantation (Childs et al, 2000;Artz et al, 2004;Rini et al, 2006), have been reported. Although these approaches have demonstrated tantalising indications of efficacy in a small group of individuals, they have not reached the threshold of therapeutic efficacy or safety.…”

Reduced-intensity unrelated cord blood transplantation for treatment of metastatic renal cell carcinoma: first evidence of cord-blood-versus-solid-tumor effect

“…However, the worldwide clinical experience of allogeneic SCT for metastatic RCC is limited, with approximately 200 cases reported in the literature. [3][4][5][6][7][8][9][10][11][12][13][14][15]24 One of the major restrictions of this approach is the requirement that transplant candidates have an HLA-identical related donor. This requirement may limit the use of allogeneic stem cell transplantation to a minority of patients with metastatic RCC.…”

“…The results of pilot reduced-intensity transplant trials for metastatic RCC are encouraging and show that responses can occur in patients with advanced metastatic disease that has failed to respond to conventional cytokine-based therapy. 1,[3][4][5][6][7][8][9][10][11][12][13][14][15] Unrelated cord blood (UCB) is considered an alternative hematopoietic stem cell source for transplantation, and its use in adult patients with hematologic disorders is increasing. [16][17][18][19][20][21] Thus far, UCB transfer has not been attempted in patients with a solid-organ malignancy such as RCC.…”

Allergenic immunotherapy for solid tumours-current and future trends

“…Artz et al ont revu la litté rature et l'expé rience de l'université de Chicago [1]. Ils ont retrouvé 14 é tudes publié es qui ont rapporté 163 patients é valuables : 32 ont pré senté une ré ponse partielle et sept une ré ponse complè te avec un taux de ré ponse globale de l'ordre de 24 %.…”