Alexei Shimanovsky

Immune alterations in malignant melanoma and current immunotherapy concepts.

Introduction: Malignant melanoma is a highly aggressive, immunogenic tumor that has the ability to modulate the immune system to its own advantage. Patients with melanoma present numerous cellular immune defects and cytokine abnormalities, all leading to suppression of the host anti-tumor immune response. Innovative treatment strategies can be achieved through employing our knowledge of the melanoma-induced immune alterations. Areas covered: The authors review comprehensively the immune abnormalities in individuals with melanoma, and provide a summary of currently available melanoma immunotherapy agents that are currently on the market or undergoing clinical trials. Expert opinion: Ipilimumab, a monoclonal antibody directed against the CTLA-4, is one of the current forefront treatment strategies in malignant melanoma. Novel immunomodulating agents have shown clear activity in patients with malignant melanoma. These include anti-PD-1 and anti-PD-1 ligand antibodies that may soon become important items in the anti-melanoma armamentarium. Combinations of different immunotherapy agents, between themselves or with other agents, are currently being studied in an attempt to further enhance the antineoplastic effect in patients with malignant melanoma.

Autoimmune manifestations in patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Background Multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS), have been linked with several autoimmune conditions in the medical literature. Yet, significance of these associations is not well understood. Methods Herein, we provide a comprehensive literature review on autoimmune disorders identified in patients with MM and MGUS. Most relevant papers were identified via searching the PubMed/Medline and EMBASE databases for articles published from inception until May 1, 2016. Findings Scientific literature on autoimmune conditions in patients with MM and MGUS consists of several case series and a multitude of case reports. Our analysis suggests an increased prevalence of autoimmune conditions in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), including various autoimmune hematologic and rheumatologic conditions among other entities. Conversely, persons with various autoimmune conditions tend to have a higher prevalence of MGUS and MM than the general population. Conclusions Future research is required to explore further the link between MGUS/MM and autoimmune disorders. Inflammation in the setting of autoimmunity may serve as a trigger for MGUS and MM. In addition, a common genetic susceptibility for developing both an autoimmune disease and MM/MGUS might also exist. Autoimmune hematologic and rheumatologic diseases may pose important clinical problems for the MM patients. Therefore, a catalogue of these problems is important so that physicians are able to consider, identify and address them promptly.

Collision tumors: pancreatic adenocarcinoma and mantle cell lymphoma.

CONTEXT Collision tumors are very rare entities composed of two or more distinct tumor components, each separated by normal tissue. Perhaps due to technical advances in the last decade, the incidence of collision tumors has been on the rise. To the best of our knowledge, collision tumors featuring mantle cell lymphoma and pancreatic adenocarcinoma have not been previously described in the scientific literature. CASE REPORT For the first time, we describe herein the clinical course of a collision tumor between pancreatic adenocarcinoma and mantle cell lymphoma. DISCUSSION We hypothesize several aspects in the pathogenesis of a such event and review the existing literature on collision tumors.

Levocarnitine and vitamin B complex for the treatment of pegaspargase-induced hepatotoxicity: A case report and review of the literature

Asparaginase is a chemotherapeutic agent that is commonly used in combination with other medications for the treatment of acute lymphoblastic leukemia. An adverse effect of asparaginase includes hepatotoxicity, which can lead to severe liver failure and death. Several reports have documented successful treatment of asparaginase-induced hepatotoxicity using levocarnitine (l-carnitine) and vitamin B complex. Herein, we report a patient with acute lymphoblastic leukemia that experienced acute liver injury following pegaspargase administration. Our patient was successfully treated with l-carnitine and vitamin B complex for 8 days and achieved recovery of hepatic function. Furthermore, we review the current literature and provide a recommendation on a regimen that can be used as an option for the treatment of asparaginase-induced hepatic injury.

Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma.

Introduction: Pralatrexate is a novel antifolate agent that belongs to the class of 10-deazaaminopterins. Its clinical efficacy as a single agent in relapsed or refractory peripheral T-cell lymphoma (PTCL) has been established in randomized trials. Treatment with this agent is generally safe. Areas covered: This paper discusses the pharmacokinetics and efficacy of pralatrexate in T-cell lymphoma in clinical trials. In addition, the authors highlight pralatrexate-associated adverse effects and safety concerns. Expert opinion: Although established as a second-line therapy, pralatrexate offers a clinical benefit to less than one-third of patients with PTCL. In addition, toxicity of this agent can be significant, especially mucositis, immunosuppression and thrombocytopenia. Currently, the potential synergy between pralatrexate and other agents in T-cell lymphoma is being explored in a number of studies. These results will hopefully prove the validity of this approach, leading to improved quantity of life in these patients, with an acceptable comfort index.

Interstitial Deletion of Chromosome 9q in Therapy-Related Acute Promyelocytic Leukemia with Pathognomonic t(15;17) in a Patient Exposed to Radioactive Iodine

Citation: Bindal P, Goel H, Shimanovsky A, Ryan JM, Wasser JS, et al. (2017) Interstitial Deletion of Chromosome 9q in Therapy-Related Acute Promyelocytic Leukemia with Pathognomonic t(15;17) in a Patient Exposed to Radioactive Iodine. Int J Blood Res Disord 4:027. doi.org/10.23937/24695696/1410027 Received: July 26, 2017: Accepted: September 27, 2017: Published: September 29, 2017 Copyright:

Updates on immunotherapy in non-small cell lung cancer

Immunotherapy has made significant progress in patients with non-small cell lung cancer (NSCLC) in the last years. Early tumor vaccine studies showed trends toward better clinical outcomes, and larger trial results are currently being awaited. Immune checkpoint inhibitors are promising therapeutic agents in advanced NSCLC. While ipilimumab, a cytotoxic T-lymphocyte antigen 4 inhibitor, has clearly improved outcomes in metastatic malignant melanoma, its safety and efficacy in NSCLC are not yet known. Programmed death-1 (PD-1) and PD-1 ligand inhibitors such as nivolumab, MK3475 and MPDL3280 have demonstrated clinical efficacy in patients with advanced/metastatic NSCLC in early clinical trials. Their validation in larger Phase III trials is anxiously being awaited. Furthermore, exploring efficacy of these molecules in patients with early stages of lung cancer is also necessary.