Pooja Motwani

Successful Management of a Possible Antibiotic-Related Acquired Factor V Inhibitor: A Case Report and Review of the Literature

Acquired factor inhibitors are rare. We report a case of an elderly male who presented with a bleeding diathesis associated with an elevated prothrombin time and an activated partial thromboplastin time. Work-up revealed undetectable factor V activity and a factor V inhibitor level of >50 Bethesda units. The inhibitor may have been triggered by antibiotics. With a multimodality approach using steroids, platelet transfusions, intravenous immunoglobulin, factor VIII inhibitor bypass activity agent and cyclophosphamide, we successfully eliminated the inhibitor and controlled the bleeding.

Targeting nano drug delivery to cancer cells using tunable, multi-layer, silver-decorated gold nanorods

Multifunctional nanoparticles have high potential as targeting delivery vehicles for cancer chemotherapy. In this study, silver‐decorated gold nanorods (AuNR\Ag) have been successfully used to deliver specific, targeted chemotherapy against breast cancer (MCF7) and prostate carcinoma (PC3) cell lines. Doxorubicin, a commonly used chemotherapy, and anti‐Epithelial cell adhesion molecule (anti‐EpCAM) antibodies were covalently bonded to thiolated polyethylene glycol‐coated AuNR\Ag, and the resultant system was used to deliver the drugs to cancer cells in vitro. Furthermore, these nanoparticles have a unique spectral signature by surface enhanced Raman spectroscopy (SERS), which enables reliable detection and monitoring of the distribution of these chemotherapy constructs inside cells. The development of interest in a plasmonic nano drugs system with unique spectroscopic signatures could result in a clinical approach to the precise targeting and visualization of cells and solid tumors while delivering molecules for the enhanced treatment of cancerous tumors.

Acquired Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab

Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition who presented with left-sided weakness and seizure-like activity preceded by headache and easy bruising. She did not achieve optimal response to plasma exchange, corticosteroids, rituximab, and vincristine. We initiated treatment with eculizumab, following which she had durable remission that continued for 30 months after discontinuation of the drug. We later found that our patient has homozygous deletion in two closely related genes, complement factor H–related 1 and complement factor H–related 3.

Acute Lymphoblastic Leukemia evolving from atypical Chronic Myelogenous Leukemia: Case Report and Review of the Literature

Atypical chronic myeloid leukemia (aCML) is a rare chronic myeloproliferative disorder characterized by leukocytosis, absence of Philadelphia chromosome or BCR-ABL rearrangement, and marked myeloid dysplasia. The diagnosis of aCML is difficult and challenging, more so if the initial presentation is with blast crisis. In the absence of characteristic mutational profile, blast crisis of aCML can lead to significant diagnostic dilemma. We describe a case of refractory acute lymphoblastic leukemia (ALL), needing critical evaluation of hemopathological and cytogenetic abnormalities. It was hypothesized that patient had undiagnosed aCML and presented with lymphoid blast crisis. To our knowledge, this is the first described case of aCML presenting with lymphoid blast crisis.

Pruritus Reduction with Systemic Anti-lymphoma Treatments in Patients with Cutaneous T Cell Lymphoma: A Narrative Review

AbstractCutaneous T-cell lymphomas (CTCL) are a heterogeneous and relatively rare group of non-Hodgkin lymphomas arising from neoplastic skin-homing memory T cells. There is no known cure for CTCL, and current treatments focus on achieving and maintaining remission, controlling symptoms, limiting toxicities and maintaining or improving quality of life. Patients with CTCL often suffer from pruritus (itching), which can be debilitating and can have a significant impact on physical well-being and quality of life. Although progress has been made towards understanding the mechanisms of pruritus, the pathophysiology of CTCL-related pruritus remains unclear. Currently, there is neither a step-wise treatment algorithm for CTCL nor a standardized approach to treating pruritus in patients with CTCL. Treatments which specifically target pruritus have been reported with varying effectiveness. However, systemic treatments that target CTCL have the potential to alleviate pruritus by treating the underlying disease. Several systemic CTCL treatments have reported anti-pruritic properties, some in both objective responders and nonresponders, but the lack of a standardized method to measure and report pruritus makes it difficult to compare the effectiveness of systemic treatments. In this review, we provide an overview of approved and investigational systemic CTCL treatments that report anti-pruritic properties. For each study, the methods used to measure and report pruritus, as well as the study design are examined so that the clinical benefits of each systemic treatment can be more readily evaluated. Funding: Financial support for medical editorial assistance and article processing charge were provided by Celgene Corporation.

Integrating Collaborative Learning and Competition in a Hematology/Oncology Training Program.

New educational methods and structures to improve medical education are needed to face the challenge of an exponential increase and complexity of medical knowledge. Collaborative learning has been increasingly used in education, but its use in medical training programs is in its infancy, and its impact is still unknown; the role of competition in education is more controversial. We introduced these pedagogical methods to the hematology/oncology fellowship program at the University of Arkansas for Medical Sciences to improve attendance and performance at didactic activities and different educational outcomes. One year after the adoption of these methods, the fellowship program has reached many of the expected goals from this intervention without the negative consequences of competition observed in younger learners. The most important conclusion of this project is that collaboration and cross-generational team work provide a healthy and effective learning environment and competition may not add further benefit. Analysis, interpretation, and discussion of our experience are provided. This study was approved by the University of Arkansas for Medical Sciences IRB as a low risk educational intervention not requiring a consent form.

Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years

ABSTRACT Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified. Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS. Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002–2015). Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n = 19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n = 12), 35% for CD68 (n = 8), 30% for CD34 (n = 7), and 26% for lysozyme (n = 6). Cytogenetic abnormalities were seen in 63% (n = 12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n = 3) or monosomal (n = 2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4–24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p = 0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p < 0.001). All patients who underwent allogeneic hematopoietic stem cell transplant attained long-term remissions, with a median follow-up of 54 (range 32–120) months. Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.

Complement Regulatory Genetic Mutations in the Setting of Autoimmune Thrombotic Thrombocytopenic Purpura: A Case Series

Objective To explore the benefits of adding eculizumab for the treatment of refractory autoimmune thrombotic thrombocytopenic purpura (iTTP) with complement dysregulation. Patients and Methods From January 1, 2014, through July 1, 2017, we identified patients with iTTP defined by ADAMTS13 (disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels less than 5% and the presence of ADAMTS13 inhibitor. Patients who progressed after receiving standard of care management for iTTP were subjected to a comprehensive evaluation to look for evidence of complement activation. Herein, we share our single-institute experience regarding the clinical course and treatment algorithm for 3 patients with refractory iTTP. Results All the patients had clinical deterioration despite treatment with plasma exchange, corticosteroids, rituximab, and vincristine, which prompted us to look for evidence of complement activation and associated genetic mutations. Complement-related genetic aberrations were present in all 3 patients, who had had different degrees of complement activation. The first 2 patients did not benefit from eculizumab when treatment was started before complete clearance of inhibitors to ADAMTS13. However, they had durable remissions when eculizumab was introduced after clearance of ADAMTS13 inhibitors. The third patient started eculizumab therapy after inhibitor levels were undetectable. Conclusion We found eculizumab therapy to be effective in all 3 patients. However, its efficacy was prominent only after clearance of antibodies against ADAMTS13 via therapeutic plasma exchange.

Heparin-induced Thrombocytopenia in Patients Receiving Plasma Exchange

Heparin-induced thrombocytopenia is a rare complication of heparin use. Based on pathogenesis, it is classified into 2 types. Type 1 thrombocytopenia is a transient decrease in platelet count, which improves spontaneously, even with continuation of heparin. Heparin-induced thrombocytopenia Type 2, which is more severe, is caused by the formation of an antibody to the heparin-platelet factor 4 complex. The binding of the antibody to the complex results in platelet activation and widespread thrombosis by platelet consumption. Heparin-induced thrombocytopenia is a clinical diagnosis. A 4T score (Timing, degree of Thrombocytopenia, Thrombosis, other causes of Thrombocytopenia) is used to assess the likelihood of heparin-induced thrombocytopenia. It is treated by the discontinuation of heparin and the initiation of a nonheparin anticoagulant. We describe 2 cases of heparin-induced thrombocytopenia that arose in patients receiving heparin while on treatment with plasma exchange for other indications. Patient 1 was a 33-year-old man admitted to our hospital with newly diagnosed acute inflammatory demyelinating polyradiculopathy. Starting on day 3 of admission, he underwent 5 sessions of plasmapheresis, on alternating days. Thrombocytopenia was noticed on day 11. A 4T score of 5 was calculated, and subcutaneous heparin, which was being used for deep vein thrombosis prophylaxis, was discontinued. Heparin antibody assay was positive, with >50% inhibition and level >0.4 optical density units. The patient was started on bivalirudin. Platelets recovered to normal range (150-450 10/L) by day 19 (Figure).