Clinical implications of KRAS mutations in advanced non-small cell lung cancer remain unclear. We retrospectively evaluated the prognostic and predictive value of KRAS mutations in patients with advanced NSCLC. Among 484 patients with available results for both KRAS and EGFR mutations, 39 (8%) had KRAS and 182 (38%) EGFR mutations, with two cases having both mutations. The median overall survivals for patients with KRAS mutations, EGFR mutations, or both wild types were 7.7, 38.0, and 15.0 months, respectively (P<0.001). The KRAS mutation was an independent poor prognostic factor in the multivariate analysis (hazard ratio = 2.6, 95% CI: 1.8–3.7). Response rates and progression-free survival (PFS) for the pemetrexed-based regimen in the KRAS mutation group were 14% and 2.1 months, inferior to those (28% and 3.9 months) in the KRAS wild type group. KRAS mutation tended to be associated with inferior treatment outcomes after gemcitabine-based chemotherapy, while there was no difference regarding taxane-based regimen. Although the clinical outcomes to EGFR tyrosine kinase inhibitors (TKIs) seemed to be better in patients with KRAS wild type than those with KRAS mutations, there was no statistical difference in response rates and PFS according to KRAS mutation status when EGFR mutation status was considered. Two patients with both KRAS and EGFR mutations showed partial response to EGFR TKIs. Although G12D mutation appeared more frequently in never smokers, there was no difference in clinical outcomes according to KRAS genotypes. These results suggested KRAS mutations have an independent prognostic value but a limited predictive role for EGFR TKIs or cytotoxic chemotherapy in advanced NSCLC.
Extranodal natural killer/T-cell lymphoma (ENKL) has a dismal prognosis. Although L-asparaginase has shown promising efficacy as a frontline therapy, currently there are no treatment options after progression to an L-asparaginase-containing regimen. We report the results of gemcitabine-containing therapy in patients with relapsed or refractory ENKL. We retrospectively reviewed 20 patients with refractory or relapsed ENKL who received a gemcitabine-containing regimen between 2005 and 2011. The overall response rate was 40% (8 of 20 patients) with a complete response (CR) rate of 20% (n = 4) and a partial response (PR) rate of 20% (n = 4). Four complete responders had a disease-free status for more than 7 months including two patients received autologous stem cell transplantation consolidation and L-aspraginase maintenance, respectively. The median progression-free survival of the 20 patients was 2.3 months; however, it was 7.3 months for eight responders (CR and PR). The median overall survival of the eight responders had not been reached at the time of analysis. Gemcitabine was effective in a subset of pretreated ENKL patients and can be considered as a salvage option.
mg administered during two or three annual cycles (12 mg or 24 mg, 3 times a week). The shorter time to ITP development observed in our study may be related to the different cumulative dose and to the different schedule of drug administration.It has been previously suggested that ITP secondary to lymphoproliferative disorders could be ascribed to autoreactive non-malignant B-cell clones, favored by the loss of immune tolerance due to T-cell dysfunction and/or inappropriate pathological (auto)antigen presentation by CLL cells [16,17]. During alemtuzumab treatment, immune-dysregulation of T lymphocytes may further favor autoimmunity.In conclusion, while reporting for the first time the association between lowdose alemtuzumab treatment and ITP in a cohort of CLL patients, we would also suggest to maintain a high level of vigilance and to strongly consider routine monitoring for ITP in patients treated with this agent for any pathologic condition. MethodsWe retrospectively analyzed a cohort of 64 patients affected by CLL, diagnosed according to NCIWG-CLL criteria and referred to the Hematology-BMT Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan between 2003 and. Median age of patients was 68 years (range: 40-83 years).Patients had been treated with low-dose Alemtuzumab, defined as a total weekly dose lower than 45 mg and a cumulative dose inferior to 600 mg, administered for up to 18 weeks [18,19,20].The diagnosis of ITP was based on (1) an otherwise unexplained, rapid (<2 weeks) and severe fall (at least half of the initial level and below 100 3 10 9 /L) of the platelet counts; (2) a normal or augmented number of megakaryocytes in the bone marrow; (3) no or limited (not palpable) splenomegaly, and (4) no cytotoxic treatment in the last month except for alemtuzumab. We also evaluated assays for antibodies to specific platelet glycoproteins, even if they are not routinely recommended, as platelet-associated IgG is elevated in both immune and non-immune thrombocytopenia [21]. Conflict of interest: Nothing to report. A.C., G.R., C.V., and F.R. designed the research study; F.M., G.G., G.R., A.G., F.B., and F.G. performed the research; F.M., G.G., A.G., and A.P. analyzed the data; A.C., G.R., F.M., G.G., C.V. wrote the paper. The impact of baseline and interim PET/CT parameters on clinical outcome in patients with diffuse large B cell lymphoma F-FDG PET/CT as a tool for guidance in risk stratification in patients with aggressive non-Hodgkin's lymphoma (NHL). Here, we analyzed the predictive value of various PET/CT parameters in patients with DLBCL. Particularly, we were interested in patients with an IPI score of 1, 2, or 3, whose prognosis are confusing. Between Jul 2008 and Feb 2010, a total of 100 patients (including 57 patients with an IPI score of 1-3) who were treated with R-CHOP for DLBCL, and had assessable PET/CT parameters were analyzed in this study. Absolute value of SUV max , SUV sum (sum of SUV max ) and TLG sum (SUV mean x Volume meta ) from baseline and interim PET/CT, and DS...
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