Case Series of Hepatosplenic T-Cell Lymphoma: A Rare and Aggressive Disease.

Hepatosplenic T-cell lymphoma is a rare form of T-cell lymphoma that predominantly emerges from neoplastic proliferation of cytotoxic T cells of γ/δ T-cell receptor-expressing lymphocytes. Isochromosome 7q and trisomy 8 are the most prevalent chromosomal abnormalities associated with hepatosplenic T-cell lymphoma, and most patients have mutations in genes related to chromatin remodeling or the JAK/STAT system. Hepatosplenic T-cell lymphoma can mimic various infectious diseases, immunological conditions, and other malignancies. Patients usually present with nonspecific constitutional symptoms and spleen and liver enlargement, with variable degrees of cytopenia. The rarity of this disease, coupled with the lack of lymph node involvement that is usually seen in lymphomas, causes significant difficulty in diagnosis, which inevitably delays the initiation of treatment. Managing this lymphoma is arduous because of its late presentation and aggressive nature, frequently resulting in rapid progression in its clinical course and refractoriness to conventional chemotherapy. There is a lack of international guidelines for its treatment, and in most cases, treatment is guided by case series. Here, we highlight the clinicopathological features and management of hepatosplenic T-cell lymphoma over a 10-year span in a single hematology referral center and review the literature.

Plasma Cell Leukemia with Successful Upfront Venetoclax in Combination with Allogeneic Transplantation.

BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.

Occult Disseminated Metastatic Breast Carcinoma Presenting as Acquired Thrombotic Thrombocytopenic Purpura.

Cancer-related microangiopathic hemolytic anemia (MAHA) is a rare and life-threatening condition. We present a patient who had been treated for invasive lobular breast carcinoma in clinical remission with fever and hemolytic anemia. The peripheral blood film showed MAHA and thrombocytopenia, and a functional deficiency of ADAMTS13 activity of 23% consistent with acquired thrombotic thrombocytopenic purpura. Bone marrow aspirate and trephine biopsy confirmed metastatic carcinoma. Further evaluation revealed the involvement of multiple bone sites without recurrence of the primary tumor. The patient received a daily plasma exchange with cryosupernatant and was pulsed with corticosteroids. MAHA related to breast cancer appears to be a rare occurrence.

A Review of Candidate Genes and Pathways in Preeclampsia-An Integrated Bioinformatical Analysis.

: Preeclampsia is a pregnancy-specific disorder characterized by the presence of hypertension with the onset of either proteinuria, maternal organ or uteroplacental dysfunction. Preeclampsia is one of the leading causes of maternal and fetal mortality and morbidity worldwide. However, the etiopathologies of preeclampsia are not fully understood. Many studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in preeclampsia. An electronic search was performed through 2019 through PubMed, Scopus, Ovid-Medline, and Gene Expression Omnibus where the following MeSH (Medical Subject Heading) terms were used and they had been specified as the primary focus of the articles: Gene, placenta, preeclampsia, and pregnancy in the title or abstract. We also found additional MeSH terms through Cochrane Library: Transcript, sequencing, and profiling. From 687 studies retrieved from the search, only original publications that had performed high throughput sequencing of human placental tissues that reported on differentially expressed genes in pregnancies with preeclampsia were included. Two reviewers independently scrutinized the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. For each study, study design, sample size, sampling type, and method for gene analysis and gene were identified. The genes listed were further analyzed with the DAVID, STRING and Cytoscape MCODE. Three original research articles involving preeclampsia comprising the datasets in gene expression were included. By combining three studies together, 250 differentially expressed genes were produced at a significance setting of p < 0.05. We identified candidate genes: LEP, NRIP1, SASH1, and ZADHHC8P1. Through GO analysis, we found extracellular matrix organization as the highly significant enriched ontology in a group of upregulated genes and immune process in downregulated genes. Studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of preeclampsia. Integrated bioinformatics could identify differentially expressed genes which could be candidate genes and potential pathways in preeclampsia that may improve our understanding of the cause and underlying molecular mechanisms that could be used as potential biomarkers for risk stratification and treatment.

Importance of extended blood group genotyping in multiply transfused patients.

Blood group antigen systems are not limited to the ABO blood groups. There is increasing interest in the detection of extended blood group systems on the red cell surface. The conventional method used to determine extended blood group antigens or red cell phenotype is by serological testing, which is based on the detection of visible haemagglutination or the presence of haemolysis. However, this technique has many limitations due to recent exposure to donor red cell, certain drugs or medications or other diseases that may alter the red cell membrane. We aimed to determine the red cell blood group genotype by SNP real time PCR and to compare the results with the conventional serological methods in multiply transfused patients. Sixty-three patients participated in this study whose peripheral blood was collected and blood group phenotype was determined by serological tube method while the genotype was performed using TaqMan® Single Nucleotide Polymorphism (SNP) RT-PCR assays for RHEe, RHCc, Kidd and Duffy blood group systems. Discrepancies were found between the phenotype and genotype results for all blood groups tested. Accurate red blood cell antigen profiling is important for patients requiring multiple transfusions. The SNP RT-PCR platform is a reliable alternative to the conventional method.