Abstract. Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients.

Summary:role of dose-intensive chemotherapy in the treatment of chemotherapy-sensitive malignancies. 1 Multiple myeloma is one example in which a clinical relationship between Attempts to increase dose intensity have been hampered by hematologic toxicity. To address this issue, we dose intensity of melphalan and response rate has been demonstrated. 2 Unfortunately, melphalan dose escalation is designed a study to determine whether the reinfusion of PBPC significantly reduces the toxicity of multicyclic limited by myelosuppression, and only a modest increase in dose intensity can be achieved with the administration dose-intensive chemotherapy. Thirty refractory patients, median age 63, received CY 3 g/m 2 plus of hemopoietic growth factors. 3,4 Administration of G-CSF following chemotherapy leads melphalan 60 mg/m 2 followed by PBPC and G-CSF (CM regimen). CY (at day 0) and G-CSF were used to to the release of a large number of PBPC, 5-7 whose quality is equivalent to that of bone marrow. 8 The infusion of mobilize PBPC harvested by a single leukapheresis at day 10. Melphalan was infused at day 11. PBPC were PBPC results in a considerable increase in dose intensity. 4,6 Sufficient PBPC for transplantation can be obtained at a kept unprocessed at 4؇C for 48 h and reinfused at day 12. This regimen was repeated three times every 6 single leukapheresis. 9 Whole blood and leukapheresis products remain viable for several days at 4°C. 10 This has led months. Outcomes were compared with those of 30 similar patients treated with melphalan 30 mg/m 2 folus to investigate the use of non-cryopreserved PBPC to support dose-intensive chemotherapy in elderly myeloma lowed by G-CSF only, and repeated every 2 months for a total of six cycles. In patients receiving CY plus patients. The significance of dose intensity is evident in refractory melphalan followed by PBPC reinfusion, the median duration of neutropenia (ANC Ͻ500/ l) and thrommyeloma patients. Oral melphalan and prednisone induced an unsatisfactory response rate of 20%. 11,12 Intravenous bocytopenia (platelets Ͻ25 000/ l) was only 5 and 2 days respectively, and did not increase after the submelphalan 25 mg/m 2 increased responses to 35%. 13 Melphalan 50 to 100 mg/m 2 resulted in a 50-60% response rate. sequent courses. Hematologic toxicity was quite similar to that observed after melphalan 30 mg/m 2 plus G-CSF.A median of 4 weeks was needed for hematological recovery, despite the use of hemopoietic growth factors. 14 In a The CM regimen was followed by 30% complete remission and 86% response Ͼ50%, melphalan recent experience, melphalan 70 mg/m 2 combined with G-CSF induced a prolonged myelosuppression in 10 pre-30 mg/m 2 by no complete remissions and 38% response Ͼ50%. Patients receiving CM regimen showed a longer viously treated multiple myeloma patients: granulocytes remained Ͻ500/ l for a median of 20 days (range 11-36) progression-free survival (22 vs 10 months, P Ͻ 0.01). The dose intensity of melphalan can be doubled by and platelets Ͻ25 000/ l for a median ...

Mantle Cell Lymphoma (MCL) is a well-known histological and clinical subtype of B-cell nonHodgkin's Lymphomas. It is usually characterized by an aggressive disease course, presenting with advanced stage disease at diagnosis and with low response rates to therapy. However few cases of indolent course MCL have been described. We herein report a case of MCL with splenomegaly and peripheral blood involvement as main clinical features. The patient underwent moderate dose splenic radiation therapy and achieved spleen downsizing and peripheral blood complete remission. Splenic irradiation has been extensively used in the past as palliative treatment in several lymphoproliferative disorders and a systemic effect and sometimes peripheral blood complete remissions have been observed. Mainly advocated mechanisms responsible for this phenomenon are considered direct radiation-induced apoptotic cell death, immune modulation via proportional changes of lymphocyte subsets due to known differences in intrinsic radiosensitivity and a radiationinduced cytokine release. The peculiar intrinsic radiosensitivity pattern of lymphoid cells could probably be explained by well-defined individual genetic and molecular features. In this context, among NHLs, MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated) inactivation. While the ATM gene is thought to play a key-role in detecting radiation-induced DNA damage (expecially Double Strand Breaks), recent in vitro data support the hypothesis that ATM loss may actually contribute to the radiosensitivity of MCL cells. ATM status was retrospectively investigated in our patient, with the tool of Fluorescence In Situ Hybridization, showing a complete inactivation of a single ATM allele secondary to the deletion of chromosomal region 11q22-23. The presence of this kind of cytogenetic aberration may be regarded in the future as a potential predictive marker of radiation response. Full textMantle-Cell Lymphoma (MCL) has been clearly recognized as a distinct histological and clinical subtype of Bcell non-Hodgkin's Lymphomas. Typical of the elderly, it has an estimated incidence of 2-3/100,000/year and accounts for 8% of all NHLs [1]. Diagnostic work-up usu-

e14657 Background: KRAS and BRAF mutations have prognostic and predictive value in colorectal cancer and are predominantly mutually exclusive. Only a few cases of double mutations (DM) have been reported so far but the actual incidence and presumed role in worsening prognosis is still unknown. Here we report on a series of KRAS and BRAF mutations, focusing on three cases of KRAS and BRAF DM. Methods: since May 2010, 316 consecutive colorectal cancer samples were collected by our Oncology Department; ten patients (3%) had high risk localized disease and 306 (97%) metastatic disease. Genome DNA from formalin-fixed paraffin embedded samples with tumor cells > 50% was analyzed by reverse dot blot with KRAS-BRAF StripAssay kit (Nuclear Laser Medicine). Results: KRAS point mutations were found in 141 patients (44.6%): 32% G12V, 30.5% G12D, 14.9% G13D, 6.4% G12S, 5.7% G12C, 4.9% G12A, 4.9% G12R, 0.7% G13C; V600E BRAF point mutation was found in 21 patients (6.6%). Three patients (1%) displayed DM: 2 KRAS G13D + BRAF V600E (A and B) and 1 KRAS G12V + BRAF V600E (C). Patients A and C, both aged 59, presented with metastatic disease. Patient A had a rectal primary, a single lung lesion and mediastinal nodes. He failed first line FOLFOX4 plus bevacizumab and underwent salvage surgery both on primary and metastatic disease. He relapsed in 3 months with liver and brain metastasis and died after one year from diagnosis. Patient B had huge liver lesions at presentation. She progressed after 3 courses of FOLFIRI and died after 6 months from diagnosis. Patient C was operated on for a right colon cancer, G3, pT2N2, stage IIIB with lymph vascular invasion and had adjuvant FOLFOX 4. The 6-month assessment did not show relapse. Conclusions: in our series KRAS mutation incidence was in line with literature, but G12V was far more frequent. KRAS-BRAF DM accounted for 1% of all cases and the 2 patients with metastatic disease had an aggressive course with a much lower than expected survival. To our knowledge no series of DM have been described, hindering the understanding of their biological meaning. According to our experience, metastatic double mutated patients do not respond to standard therapy and should be treated with new drugs combinations in clinical trials.

No abstract