Efficacy of host-dendritic cell vaccinations with or without minor histocompatibility antigen loading, combined with donor lymphocyte infusion in multiple myeloma patients.

Donor lymphocyte infusions (DLI) can induce durable remissions in multiple myeloma (MM) patients, but this occurs rather infrequently. As the graft-versus-tumor (GvT) effect of DLI depends on the presence of host-dendritic cells (DCs), we tested in a phase I/II trial whether the efficacy of DLI could be improved by simultaneous vaccination with host-DCs. We also analyzed the possibility of further improving the GvT effect by loading the DCs with peptides of mismatched hematopoietic cell-specific minor histocompatibility antigens (mHags). Fifteen MM patients not responding to a first DLI were included. Eleven patients could be treated with a second equivalent dose DLI combined with DC vaccinations, generated from host monocytes (moDC). For four patients, the DC products did not meet the quality criteria. In four of the treated patients the DCs were loaded with host mHag peptides. Toxicity was limited and no acute GvHD occurred. Most patients developed objective anti-host T-cell responses and in one patient a distinct mHag-specific T-cell response accompanied a temporary clinical response. These findings confirm that DLI combined with host-DC vaccination, either unloaded or loaded with mHag peptides, is feasible, safe and capable of inducing host-specific T-cell responses. The limited clinical effects may be improved by developing more immunogenic DC products or by combining this therapy with immune potentiating modalities like checkpoint inhibitors.

Hand-assisted laparoscopic donor nephrectomy. Ascending the learning curve.

BACKGROUND: The hand-assisted approach to laparoscopic donor nephrectomy (LDN) might minimize the learning curve and shorten both the operation and the warm ischemia time. Our initial results from hand-assisted LDN are presented and compared with data from the literature. METHODS: From January to September 2000, ten hand-assisted LDNs of the right kidney were performed. RESULTS: The median operation time was 140 min (range, 120-400 min), and the warm ischemia time was 2.5 min (range, 1-4 min). There were no conversions. Postoperative morbidity included one urinary tract infection. All but one patient returned to a normal diet within 48 h. Opiates were needed a maximum of 48 h. One recipient experienced initial loss of graft function as a result of unknown causes. CONCLUSIONS: Even at the beginning of the learning curve, operation time and warm ischemia time are significantly reduced by the hand-assisted approach, as compared with conventional LDN.

Resectable retroperitoneal soft tissue sarcomas. The effect of extent of resection and postoperative radiation therapy on local tumor control.

BACKGROUND: Soft tissue malignancies of the retroperitoneum are rare. Surgery is commonly considered the first choice of treatment. There is still no consensus concerning the precise value of the extent of surgery and the value of additional treatment modalities. METHODS: From 1973 to 1990, 34 patients were initially treated by surgery for retroperitoneal soft tissue sarcomas at the Netherlands Cancer Institute. In a retrospective study, the prognostic effect of extent of primary surgery and postoperative radiation therapy was examined. RESULTS: Liposarcomas (47%) and leiomyosarcomas (29%) were the histologic types most commonly found. Grade of malignancy was defined as medium to high (II/III) in 44% and as low (I) in 38%. Complete (extended or marginal) resection of the tumor was achieved in 29 patients. After complete resection, the 5-year survival rate and the local recurrence rate were 35% and 63%, respectively. Extended surgery (performed in eight patients) showed a local recurrence rate of 50%. Thirteen patients received high-dose postoperative radiation therapy, which was found to have a significant favorable effect on the recurrence-free interval (P < 0.01). CONCLUSIONS: We conclude that complete (extended) resection followed by high-dose postoperative radiation therapy improves the prognostic outcome of patients with retroperitoneal soft tissue sarcomas.