Clinical and genetic characteristics in lymphoma patients with a second solid malignancy

Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the clinical and genetic features of multiple primary malignancies in patients with synchronous or metachronous lymphoma and another solid tumor. We retrospectively analyzed 11 cases with lymphoma and another solid tumor. The germline mutations in plasma cell-free DNA samples and somatic mutations in lymphoma and solid tumor tissue samples were identified using targeted next-generation sequencing. In the 11 lymphoma patients, the most common type of concurrent solid tumor was colon adenocarcinoma (case 3, 5, 9 11) followed by papillary thyroid carcinoma (case 1, 7, 10). Metachronous lymphoma and solid tumor in 6 patients were treated with corresponding standard therapy asynchronously. Chemotherapy for colon adenocarcinoma during the interval of lymphoma chemotherapy led to excellent outcome in two patients. Immediate chemotherapy for lymphoma plus elective surgery for synchronous papillary thyroid carcinoma also yielded good prognosis in two patients with synchronous double primaries. Interestingly, we found that 10 of 11 patients with lymphoma and another solid tumor harbored germline mutations in Fanconi anemia complementation group (FANC) genes, including FANCI, FANCA, FANCG, FANCL, FANCD1, FANCF, FANCJ, and FANCS. In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy

Carfilzomib in multiple myeloma: unraveling cardiac toxicities - from mechanisms to diagnosis and management

The survival rates of patients with hematological malignancies such as multiple myeloma have improved with advances in cancer treatment. However, the risk of cardiovascular disease associated with novel therapeutic agents, including proteasome inhibitors (PIs), is becoming increasingly evident. PIs act on proteasome peptidases, leading to cell cycle arrest or apoptosis. Carfilzomib (CFZ), an intravenously administered irreversible PI, exhibits pronounced cardiovascular toxicity that is characterized by heart failure, hypertension, arrhythmia, and ischemic heart disease (IHD). This review focuses on CFZ, details its applications in treating multiple myeloma, presents its potential mechanisms of cardiotoxicity and the incidence of cardiotoxic events, and provides recommendations for the evaluation and management of adverse cardiac events during the early treatment of patients with this drug

A rapid evaluation method for design strategies of high-rise office buildings achieving nearly zero energy in Guangzhou

The construction of nearly zero energy buildings (NZEB) has achieved dramatical impact on global warming and energy crises. It is still a challenge for designers to derive design strategies on how to achieve NZEB in the early design stage, because a complex modelling process with many input parameters of the current NZEB design and evaluation tool is still unavoidable. This article, therefore, aims to introduce a tool suitable for the rapid and reliable evaluation of NZEB design strategies for high rise office building in the city of Guangzhou in China. Firstly, a high-rise office building with typical geometry features is established by sensitivity analysis and survey, thereby the reference building consumption is obtained. Secondly, comprehensive simulations on cases with various envelope features, air conditioning performances and lighting control methods is carried out. Based on the sensitivity analysis on simulation results, key influencing parameters are selected out, effective strategies which fulfills "Technical standard for nearly zero energy buildings (NZEBTS)" are put forward. Finally, a parametric building energy evaluation model is built by regression analysis on simulation results. Combined with energy efficiency index from "NZEBTS", an evaluation tool is developed to help designer determine NZEB strategies. The results revealed that the most effective strategies to achieve NZEB in Guangzhou are to apply high performance external windows, improve air conditioning systems and utilize intelligent zone-controlled lighting systems, meanwhile, the utilization ratio of renewable energy (eta(s)) should be more than 40% of building total annual energy consumption

Blastic plasmacytoid dendritic cell neoplasm with genetic mutations in multiple epigenetic modifiers: a case report

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematodermic malignancy derived from plasmacytoid dendritic cell precursors. Despite advances in our understanding of tumor cell surface markers, the pathogenesis of BPDCN remains largely unknown. No standard or optimal treatments are available for BPDCN, and the prognosis is usually poor. We report herein a case of BPDCN that harbored multiple genetic mutations in epigenetic modifiers such as TET2 and ZRSR2. Genetic studies in patients with BPDCN may provide insights into the underlying pathogenesis, prediction of clinical prognosis, and development of better targeted therapeutics for this rare clinical entity. </jats:p

Patient-derived xenograft mouse model for personalized treatment in patients with multiple myeloma

Abstract Background: This study aimed to establish patient-derived xenografts (PDX) models of multiple myeloma and to evaluate the feasibility of using the PDX model to test chemotherapy responsiveness. Methods: Three patients with multiple myeloma were enrolled. Fresh multiple myeloma cells isolated from bone marrow or ascites samples were inoculated subcutaneously into flanks of NCG mice. Then, engrafted tumor pieces were inoculated into flanks of NCG mice. When tumor volumes reached 100–300 mm3, the mice were divided into groups to receive corresponding chemotherapy treatments. The volume and weight of tumors were quantified.Results: The first patient responded well to BCD (bortezomib, dexamethasone, and cyclophosphamide) chemotherapy, so did the patient’s PDX model. The second patient did not response to BCD, nor the patient’s PDX model. The third patient had a transient remission after treated with BCD, MPT (melphalan, prednisone, and thalidomide), or ILD (ixazomib, lenalidomide, and dexamethasone) regimens. The third patient’s PDX model, at least partially, responded to these regimens. Conclusion: Drug responses of the patients with multiple myeloma and their PDX mouse models were consistent. The PDX mouse model is a valid experimental platform that can be utilized in a clinical setting to select personalized therapies for patients with multiple myeloma.</jats:p

Patient-Derived Intrafemoral Orthotopic Xenografts of Peripheral Blood or Bone Marrow from Acute Myeloid and Acute Lymphoblastic Leukemia Patients: Clinical Characterization, Methodology, and Validation

Abstract Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are malignant clonal diseases of the hematopoietic system with an unsatisfactory overall prognosis. The main obstacle is the increased resistance of AML and ALL cells to chemotherapy. The development and validation of new therapeutic strategies for acute leukemia require preclinical models that accurately recapitulate the genetic, pathological, and clinical features of acute leukemia. A patient-derived xenograft (PDX) model is established by transplanting patient tumor tissue or cells into immunocompromised or humanized mice. They closely resemble human tumor progression and microenvironment and are more reliable translational research tools than other models. A patient-derived orthotopic xenograft (PDOX) model that transplants tumor cells into the corresponding anatomical site in mice better recapitulates human tumor behavior than subcutaneous or intravenous xenografts. In this study, we established bone marrow and peripheral blood cell models of AML and ALL patients, characterized their pathology, cytology, and genetics, and compared the model's characteristics and drug responsiveness with those of the corresponding patients.</jats:p

Langerhans cell histiocytosis with multisystem involvement in an infant: A case report

Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells, with a wide range of clinical presentations that vary from a solitary lesion to more severe multifocal or disseminated lesions. The disease can affect any age group; however, the peak incidence rate is in infants aged between 1 and 3 years-old. Diagnosis of LCH should be based on the synthetical analysis of clinical presentations, in addition to features of imaging and histopathology. Although certain cases regress spontaneously, other patients require systemic chemotherapy together with the administration of steroids. The present study reports the case of an infant with LDH with multisystem involvement, including that of the bone, skin, orbit, spleen and lungs. The patient received chemotherapy and obtained rapid improvement in the involved systems. A total of 2.5 years after completion of the therapy, the patient still remains in follow-up and no evidence of active disease has been noted