MART-1 TCR gene-modified peripheral blood T cells for the treatment of metastatic melanoma: a phase I/IIa clinical trial.

Background: Adoptive cell therapy with peripheral blood T cells expressing transgenic T-cell receptors (TCRs) is an innovative therapeutic approach for solid malignancies. We investigated the safety and feasibility of adoptive transfer of autologous T cells expressing melanoma antigen recognized by T cells 1 (MART-1)-specific TCR, cultured to have less differentiated phenotypes, in patients with metastatic melanoma. Materials and methods: In this phase I/IIa trial, peripheral blood T cells from HLA-A2∗02:01-positive patients with unresectable stage IIIC/IV melanoma expressing MART-1 were selected and stimulated with anti-CD3/CD28 beads, transduced with a modified MART-1(26-35)-specific 1D3 TCR (1D3HMCys) and expanded in interleukin (IL)-7 and IL-15. Patients received a single infusion of transgenic T cells in a dose-escalating manner. Feasibility, safety and objective response rate were assessed. Results: Twelve pretreated metastatic cutaneous (n = 7) and uveal (n = 5) melanoma patients were included. Patient 1 received 4.6 × 109 1D3HMCys T cells and experienced grade 5 toxicity after 9 days. Subsequent patients received 5.0 × 107 [n = 3; cohort (c) 2], 2.5 × 108 (n = 2; c3) and 1.0 × 108 (n = 6; c4) 1D3HMCys T cells. The study was prematurely terminated because of dose-dependent toxicity, concerning skin (10/12), eyes (3/12), ears (4/12) and cytokine release syndrome (5/12), with 7 patients experiencing grade 3-5 toxicity. Partial responses were seen in 2/11 (18%) assessable patients and persistence of 1D3HMCys T cells corresponded to infused cell dose. Conclusions: Production of TCR-modified cells as described leads to highly potent T cells. Partial responses were seen in 18% of patients with dose-dependent 'on-target, off-tumor' toxicity and a maximum tolerated dose of 1.0 × 108 cells.

Compression stockings after endovenous laser ablation of the great saphenous vein: a prospective randomized controlled trial.

OBJECTIVES: To determine if the duration of wearing compression stockings after endovenous laser ablation (EVLA) of the great saphenous vein (GSV) has influence on pain and quality of life. METHODS: This was a prospective randomized controlled trial. Between December 2006 and February 2008, 109 consecutive patients with EVLA of the GSV were analyzed. Deep vein insufficiency, ulceration, more than one insufficient vein in one leg, and use of anticoagulants were exclusion criteria. Group A used compression stocking for 48 hours after therapy, group B for 7 days. Pain (visual analogue scale [VAS]) and quality of life (SF-36) were analyzed 48 hours, 1 week, and 6 weeks after therapy. Three months after treatment, duplex ultrasound imaging was performed to assess occlusion rates. RESULTS: Both groups (group A, n = 37; group B, n = 32) where comparable at baseline. After 1 week, there was a significant difference in pain (VAS score 3.7 [± 2.1] vs. 2.0 [± 1.1], p ≤ .001), and physical dysfunction (group A, 85.1 [± 11.2] vs. group B, 95.7 [± 10.1]; p < .001) as well as vitality (group A, 75 [± 13.0] vs. group B, 83.7 [± 13.4]; p = .03), all in favor of group B, which disappeared after 6 weeks. After 6 weeks, no significant differences in all endpoints were present. Duplex ultrasound imaging revealed complete GSV occlusion in all patients, while no cases of deep venous thrombosis had developed. CONCLUSIONS: Prescribing compression stockings for longer than 2 days after endovenous GSV ablation (without simultaneous phlebectomies) leads to reduced pain and improved physical function during the first week after treatment.

[Lymphoma in patients who have undergone organ transplantation: severe and variable clinical presentation]. / Lymfoom bij patiënten na een orgaantransplantatie: ernstig en variabel ziektebeeld.

Two patients presented with post-transplant lymphoproliferative disorder (PTLD). PTLD encompasses a broad range ofoften malignant proliferations of lymphoid tissue arising in the immunocompromised host after transplantation. The first patient, a 62-year-old woman, received a bilateral lung transplant due to end-stage emphysema and was diagnosed with PTLD 27 days after transplantation. Treatment consisted of reduction in immunosuppression and administration of rituximab. The PTLD regressed. The second patient, a 57-year-old woman, presented with a massively disseminated PTLD 12 years after kidney transplantation. Immunosuppression was reduced and rituximab was administered, but no response was observed. Despite salvage chemotherapy, the patient died due to progressive disease. These two cases illustrate the heterogeneous presentation of PTLD. The condition is caused by the proliferation of B lymphocytes infected with Epstein-Barr virus (EBV) that are no longer controlled by EBV-specific cytotoxic T lymphocytes, due to the immunosuppressive medication given to prevent transplant rejection. Regression of the lymphoma may be achieved by reducing the immunosuppression or treating with rituximab, which attacks B lymphocytes.