Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Abstract

Although preliminary results suggest that allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the low patient number in previous studies had limited ability to evaluate the true benefit of allo HCT in OC. This retrospective multicenter study included 30 patients with OC allografted between 1995 and 2005 to determine the outcome of patients with OC treated with allo HCT. Prior to allo HCT, patients were in complete response (n 5 1), partial response (n 5 7), stable disease (n 5 11) or had progressive disease (n 5 13). An objective response (OR) was observed in 50% (95% CI, 33-67) of patients. Three patients of responding patients had an objective response following the development of acute graft-versus-host disease (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18-50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year, respectively. With a median follow-up of 74.5 months (range 16-148), median progression free survival (PFS) was 6 months and median overall survival (OS) was 10.4 months. Patients who developed cGvHD following allo HCT had a significant OS improvement compared to those who did not (17.6 months vs. 6.5 months, p 5 0.042). However, PFS was not similarly significantly improved in patients who developed cGvHD (12 months versus 3.7 months, p 5 0.81). Allo HCT in OC may lead to graft-versus-OC effects. Their clinical relevance remains to be shown.Ovarian cancer (OC), the fifth-leading cause of death for women in the United States and Europe, is the most deadly of the gynecologic malignancies. 1 Current systemic therapy consists of a combination of carboplatin and paclitaxel. Even after extensive surgery and chemotherapy, up to 50% of patients suffer from relapsing disease. Median overall survival (OS) for patients after recurrence is $2 years. 2 To improve outcome, high-dose chemotherapy regimens have been tried usually based on carboplatin combinations. These appear to delay relapse but have no influence on OS. [3][4][5] Allogeneic hematopoietic stem cell transplantation (allo HCT) is an effective therapy for many hematological malignancies. The therapeutic benefit of allogeneic transplantation relies not only on high-dose chemotherapy administered before transplantation but also is largely related to an immune-mediated graft-versus-leukemia effect, due to transplantation of the donor's immune system along with the hematopoietic tissue. Recent data from experimental animal models and from preliminary clinical experience suggest that a graft-versus-tumor effect, analogous to the graft-versusleukemia effect, may be generated against solid tumors such as renal cell cancer, breast cancer and OC. 6 Regarding OC, immunotherapy agents such as systemic or intraperitoneal interleukin-2 7-9 and adoptive transfer of tumor-infiltrating lymphocytes 10 have been used with success, testifying to the

Graft-versus-cancereffect and innovative approaches in the treatment of refractory solid tumors

“…Another retrospective multicenter study including 30 OC patients receiving allografts reported that the presence of chronic GvHD was associated with a significantly higher overall survival (OS) rate (17.6 months vs. 6.5 months, P < 0.05). An objective response rate of 50% and TRM of 20% were reported at the end of first year [67]. Median OS was 10.4 months with a median follow-up of 74.5 months (range 16-148 months).…”

Review of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in solid tumors excluding breast cancer

“…This data supports the existence of a graft-versus-ovarian cancer effect in correlation with GvHD. In another retrospective multicenter study with 30 allografted OC patients, objective response was observed in 50% and TRM was 20% at the end of first year[68]. The median overall survival was 10.4 mo with a median follow-up of 74.5 mo (16-148).…”

Graft versus tumor effect against neuroblastoma: a case report with long-term survival and a review of the literature

“…4,10 In patients with certain kinds of solid tumor, cGVHD is associated with long-term survival. 11,12 Although a study of neuroblastoma showed no advantage of GVHD, it should be noted that statistical analysis of relapse evaluating the impact of cGVHD could not be performed because of the low incidence of cGVHD.…”