Dear Editor, Kaposi sarcoma (KS) is an angiogenic proliferative disease that is associated with a human herpesvirus-8 (HHV-8) infection. 1 HHV-8 is an oncogenic virus, also associated with other conditions, such as primary effusion lymphoma or multicentric Castleman's disease (MCD). 1 So far, the role of antivirals in the management of HHV-8-induced KS is not fully explored. In this study, we present the administration of adjuvant long-term valganciclovir as a potential therapeutic option for the treatment of KS.
We analyzed the use of low-dose alemtuzumab in a cohort of 158 consecutive patients who underwent allogeneic PBSC transplantation. Patients with high-risk acute leukemia were prospectively screened for prophylactic donor lymphocyte infusion (pDLI). Lymphocytes were administered repeatedly at low and non-escalating doses (0.5-1 × 10/kg). Low-dose alemtuzumab was effective in prevention of acute GvHD after sibling or well-matched unrelated transplantation, whereas a more intensified approach was needed after mismatched transplantation. The cumulative incidence of chronic moderate/severe chronic-GvHD (cGvHD) was 15.6%. In total, 63 high-risk leukemia patients were eligible for pDLI. Only 1 out of the 39 pDLI recipients relapsed as compared with 7 out of the 24 recipients, who did not receive pDLI due to logistical hurdles. In multivariate analysis, the use of adjuvant lymphocyte therapy was significantly associated with reduced incidence of relapse and improved disease-free survival. In summary, low-dose alemtuzumab confers to a low cGvHD incidence and the administration of pDLIs in this context is very likely to reduce relapse risk in high risk leukemia patients. This is translated in an estimated 5-year probability of GvHD-free and relapse-free survival of 43.3% for the 136 leukemia patients.
Objective: The role of the sympathetic nervous system (SNS) in tumor development, progression and metastasis is studied for more than half a century and is attracting more attention during the last years. In this narrative review, we aim to a chronological and methodological presentation of the most interesting and pioneering studies on the subject. Methods: The complexity of the autonomic nervous system's interaction with the immune system, its direct and indirect effects on tumors and their surrounding tissues, plus the diversity and heterogeneity in the design and methodology of the studies, provide hard-to-interpret data and, at times, controversial findings. Studies are categorized into four main groups regarding the distribution of sympathetic nerve fibers inside the tumor, the effect of sympathectomy on cancer progression, the role of neurotransmitters on tumor growth and the impact of sympathetic adrenergic signaling on the anti-tumor immune response. Results: Studies from all four categories converge to a common point. There is strong evidence that SNS function plays a role in the development and progression of tumors and subsequently the modification of SNS function, locally or diffusely, can affect the course of tumor growth. Conclusion: The impact of SNS function on cancer behavior may be exerted in two ways, directly via the sympathetic nerve fibers or through widely distributed neurotransmitters. Modification of them, combined or not with treatments altering the immune function, could be the target for future therapeutic implications.
Introduction: Combination chemoptherapy regimens such as CHOP and MACOP-B with or without RT are considered the standard first-line treatment for PMLBCL patients. Consolidation with high dose therapy and autologous stem cell support (HDT-ASCT) at first remission is an alternative approach for this young population. However results are not optimal. Given the superiority of R-CHOP over CHOP in elderly patients with diffuse large B-cell lymphoma, the role of Rituximab added to first-line chemotherapy in younger patients is not clear. Aims: In this study we evaluate the effectiveness of R-CHOP±RT in PMLBCL and we compare the results of this strategy to CHOP±RT in historical controls. Patients and Methods: A total of 46 patients with PMLBCL were treated in two participating centers between 1994 and 2004. At a given timepoint R-CHOP replaced CHOP in both centers. Thus, 31 consecutive historical controls were treated with CHOP prior to that point and were compared to 15 patients who received R-CHOP thereafter. Results: The median age of the patients was 31 years (17–58) and 32/46 (70%) were females. Baseline characteristics between the R-CHOP and CHOP groups were well balanced, including age-adjusted IPI [ ≥2 in 40% of R-CHOP and 42% of CHOP-treated patients (p=0.90)]. Complete response (CR) was achieved in 100% in the R-CHOP±RT vs 61% in the CHOP±RT group (p=0.009). No patient has relapsed after R-CHOP, while all relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 100% and 47±9% for patients treated with R-CHOP±RT and CHOP±RT respectively(p=0.005). Within the subgroup of patients with L/LI risk IPI the corresponding 3-year FFS rates were 100% vs 61±11% (p=0.059), while they were 100% vs 26±13% (p=0.02) among patients with HI/H risk IPI for R-CHOP±RT and CHOP±RT respectively. The 3-year event free survival (EFS) was 93±7% vs 47±9% (p=0.02). The 3-year overall survival was 93±7% vs 47±9% (p=0.27), while the 3-year lymphoma specific survival was 100% vs 67±9% (p=0.049) for the R-CHOP and CHOP groups respectively. Conclusions: R-CHOP±RT exhibited impressive efficacy with no failures among 15 patients. CR and FFS rates were significantly better in favor of R-CHOP compared to CHOP-treated historical controls. EFS and lymphoma specific survival were also improved. Based on these data, our standard approach for PMLBCL patients is the application of R-CHOP±RT. Furthermore the addition of Rituximab to front-line treatment might overcome the need for more aggressive strategies such as consolidation with HDT-ASCT in this patient population.
After 35 years of research in HIV infection, resulting in the development of almost 30 disease-specific drugs, the infection has evolved, from a lethal disease, to a chronic state that in many cases does not compromise life expectancy of infected individuals. Despite this immense progress, a widespread mechanism of virus eradication has not yet been recorded, rendering individuals committed to combined drug regiments for life. As a result, these patients often face several difficulties that are associated with side effects, adhesion to therapy and/or emerging resistance of the virus to the applied regiment.On this regard, scientists have recently focused on manipulating responses of the hosts' immune system, in order to control viral replication and eventually succeed in eliminating the virus in infected individuals. Research will verify the rationale of this syllogism, which according to the authors of this article, is the only approach that can permanently heal infected patients from HIV.
BackgroundMicrovasculopathy of systemic circulation in patients with Systemic Sclerosis (SS) is widely assessed by digital capillaroscopy (DC), a method that evaluates the architecture of capillary network and reveals changes of vascular anatomy. On the other hand, ergospirometry (ERG) reveals functional impairment of microcirculation by assessing indirect measures of peripheral tissue ischemia (most suitable VE/VCO2). Since today, there have been studies correlating DC findings with spirometric parameters (respiratory volumes)1,2; nevertheless, no reports have been published correlating the same DC findings with ERG parameters (functional microvascular perfusion).ObjectivesTo propose the use of DC as a screening tool for impaired functional microvasculopathy by investigating correlations between patterns of capillaroscopic findings with ergospirometric values of peripheral tissue blood perfusion.Methods11 patients (11 women mean age 43+/- 12 ys) with SS were evaluated contemporary with High Resolution Computed Tomography of the chest, ERG, and DC. Parameters were correlated with multiple regression analysis. Statistic significance was considered p<0.05.ResultsPatient data are shown in the table.Diffuse scleroderma6/11Limited scleroderma5/11Pulmonary hypertension4/11History of digital ulcers5/11Time of endurance in minutes (ergospirometry)5':32” (±65”)Diffusion capacity (%pred)82±15Pulmonary fibrosis7/11VE/VCO2 (mean values ± sd)32±5Patterns of capillaroscopy1/11 normal 1/11 early 4/11 active 5/11 latePatients with late pattern in capillaroscopy had less endurance in exercise test (P<0.05) but no correlation was found between capillaroscopic pattern and VE/VCO2 (P>0.05). Age was a crucial confounding factor.ConclusionsThe correlation of late pattern capillaroscopy findings with reduced ergospirometric endurance in 11 patients indicates that in a larger cohort, specific parameter associations between DC and ERG are probable to emerge.References Ghizzoni C, Sebastiani M, Manfredi A, et al. Prevalence and evolution of scleroderma pattern at nailfold videocapillaroscopy in systemic sclerosis patients: Clinical and prognostic implications. Microvasc Res. 2015 May; 99: 92–5.Castellví I, Simeόn-Aznar CP, Sarmiento M, et al. Association Between Nailfold Capillaroscopy Findings and Pulmonary Function Tests in Patients with Systemic Sclerosis. J Rheumatol. 2015 Feb; 42(2): 222–7. Disclosure of InterestNone declared
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