ABSTRACT
Primary B cell lymphomas of the skull base are uncommon and lack well-defined treatment guidelines. We report a case of diffuse, large B-cell lymphoma of the cavernous sinus with sphenoid sinus and clivial extension, treated with partial resection, chemotherapy, and proton beam irradiation. To our knowledge, this is the first report of a skull-base lymphoma treated with protons. A 53-year-old female presented with a two-month history of diplopia, persistent headaches, and paresthesia over the left side of her mouth. A skull MRI revealed an enhancing mass in the right cavernous sinus and right sphenoid sinus. Transsphenoidal subtotal resection of the mass confirmed the presence of a diffuse, large B-cell lymphoma. Treatment consisted of CHOP-R chemotherapy and locoregional radiation with protons. Locoregional radiation of the lesion required moderate doses, below the radiation tolerance of adjacent normal structures. Conformal protons were utilized to minimize the volume of normal brain receiving radiation. Conformal proton beam radiotherapy to a moderate dose proved valuable in this case because it minimized the volume of normal brain receiving low to moderate doses of radiation.
Subject(s)
Lymphoma, B-Cell/radiotherapy , Protons , Skull Base Neoplasms/radiotherapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cavernous Sinus/diagnostic imaging , Cavernous Sinus/pathology , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Diplopia , Doxorubicin/therapeutic use , Female , Headache , Humans , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/drug therapy , Middle Aged , Prednisone/therapeutic use , Rituximab , Skull Base Neoplasms/diagnosis , Skull Base Neoplasms/drug therapy , Tomography, X-Ray Computed , Vincristine/therapeutic useABSTRACT
The combined effects of RAD and Neoral were tested in a rat orthotopic small-bowel transplantation model. Seven groups (n = 6) were involved in this study, and each one was included in three rejection models for the evaluation of host-vs.-graft disease (HVG) (LBN-F1 to LEW), graft-vs.-host disease (GVH) (LEW to LBN-F1), and combined HVG and GVH immune responses (BN to LEW). Both drugs were administered orally throughout the study. Low doses of RAD (1.0-2.5 mg/kg/day) combined with Neoral (2.0-5.0 mg/kg/day) produced strong synergistic effects in the prolongation of small-bowel graft survival in HVG (combination index, CI = 0.095, 0.1212), GVH (CI = 0.027, 0.020), and combined HVG and GVH immune responses (CI = 0.070, 0.301). The combination therapy of RAD and Neoral produces a strong synergistic effect toward the inhibition of HVG, GVH, and combined HVG and GVH immune responses in a rat small-bowel transplantation model.
Subject(s)
Cyclosporine/administration & dosage , Graft Rejection/prevention & control , Graft vs Host Disease/prevention & control , Host vs Graft Reaction/drug effects , Intestine, Small/transplantation , Organ Transplantation , Sirolimus/administration & dosage , Administration, Oral , Animals , Drug Synergism , Everolimus , Graft Rejection/immunology , Graft vs Host Disease/immunology , Host vs Graft Reaction/immunology , Immunosuppressive Agents , Male , Models, Animal , Rats , Rats, Inbred BN , Rats, Inbred Lew , Sirolimus/analogs & derivativesABSTRACT
BACKGROUND: Malononitrilamide 715 (FK778) is a new class of low-molecular-weight immunosuppressant that is a derivative of the active metabolite of leflunomide, A77 1726. In this study, the authors evaluated the combined effect of FK778 with tacrolimus in prevention of renal allograft rejection in Vervet monkeys. METHODS: Male Vervet monkeys were obtained from Caribbean Primates Ltd. Donor and recipient monkeys were from different breeding colonies. Eleven groups (n>or=4 per group) were involved in this study. FK778 and tacrolimus were administered orally for 60 days according to protocol. RESULTS: Naive controls rejected renal grafts, with a median survival time (MST) of 8.0 days in group 1. When recipient monkeys were treated with tacrolimus 1.0 mg/kg/day in group 2 or FK778 2.5 mg/kg/day in group 3, the MST was 16.0 days (P=0.001) and 11.0 days (P=0.266), respectively. Combination therapy of these two agents at the same doses immediately after transplantation resulted in an MST of 25.0 days (P=0.016) in group 4. When tacrolimus was initiated immediately after transplantation and FK778 treatment was delayed until day 7 after surgery in group 5, recipient survivals were significantly prolonged to 38.0 days (P=0.02). These results were repeatable when FK778 5.0 mg/kg/day (9.0 days, P=0.544 in group 6) was combined with tacrolimus 1.0 mg/kg/day immediately after transplantation (8.0 days, P=0.339) in group 7, or when FK778 was delayed 7 days (60.0 days, P=0.002) in group 8. Furthermore, it was also repeatable when FK778 10 mg/kg/day was combined with tacrolimus 1.0 mg/kg/day with a 7-day delay. CONCLUSIONS: A significant prolongation of renal allograft survival was produced when FK778 administration was delayed by 7 days combined with tacrolimus in Vervet monkeys.
