Acquired Hemophilia A in a Patient With Multiple Sclerosis.

Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against clotting factor VIII. It occurs most commonly in the elderly population. AHA is associated with malignancy, autoimmune diseases, pregnancy, and drugs. However, up to 50% of reported cases remain idiopathic. AHA is very rarely associated with multiple sclerosis. Case Presentation A 56-year-old patient with a history of MS presented with thigh and arm swelling and associated pain. Imaging revealed diffuse iliopsoas hematoma. Laboratory studies showed that prothombin time was not elevated and there was prolongation of activated partial thromboplastin time that was not corrected by mixing studies. Clotting factor VIII activity level was reduced, and the inhibitor level was elevated. He was treated with factor eight inhibitor bypassing agents, rituximab, and steroids. Conclusion AHA should be suspected in any patient with new-onset bleeding in the presence of a prolonged activated partial thromboplastin time. Prompt diagnosis and treatment are important as AHA carries a high mortality rate.

Intravascular Large B-Cell Lymphoma: A Diagnostic Dilemma.

Intravascular large B-cell lymphoma is a rare malignancy characterized by the presence of lymphoma cells within the lumen of blood vessels. The annual incidence of cases is fewer than 0.5 cases per 1,000,000. It usually affects the elderly with an average age of diagnosis around 70 years. Due to the absence of lymphoma cells in the peripheral smear and lymphadenopathy, it is difficult to diagnose these cases. Although the central nervous system and skin are the commonly involved organs, they can involve any organ system. Prompt diagnosis and initiation of treatment are very crucial as it carries a high mortality. We describe two patients who presented with constitutional symptoms and fever of unknown origin, later diagnosed as intravascular large B- cell lymphoma. The diagnosis was difficult in both cases as the presenting symptoms were atypical. One of the patients was diagnosed at autopsy. The delay in diagnosis often leads to fatal outcomes as the disease is very aggressive. A high degree of clinical suspicion is the key to prompt diagnosis and improved outcomes.

Salvage Radiation Treatment for Primary Refractory Diffuse Large B-cell Lymphoma After Chimeric Antigen Receptor (CAR) T-cell Therapy: A Case Report.

BACKGROUND: Treatment of refractory/relapsing diffuse large B cell (R/R DLBCL) lymphoma remains a challenge. Radiation therapy (RT) has versatile roles in R/R DLBCL treatment: it can be used in the peri-transplant setting for transplant-eligible candidates, or as a salvage or palliation therapy depending on the extent of the disease in transplant-ineligible patients. The introduction of chimeric antigen receptor (CAR) T-cell therapy has changed the landscape of R/R DLBCL. RT has been used as a bridging therapy to CAR T-cell therapy in order to control disease progression during its manufacturing period. However, optimal RT and CAR T-cell therapy integration is still unknown. Salvage strategies for R/R DLBCL post-CAR T-cell therapy have been little studied. CASE REPORT: Here, we present a case of primary refractory DLBCL with residual disease post-CAR T-cell therapy successfully treated with salvage RT. CONCLUSION: Radiotherapy could be an effective salvage strategy for R/R DLBCL post-CAR T-cell therapy. Exact mechanisms await exploring.

Remission of refractory granulomatous primary cutaneous anaplastic large cell lymphoma to brentuximab vedotin.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare non-Hodgkin's lymphoma that arises as a single, or multiple dome-shaped tumours on the skin. The histology is characterised by the presence of atypical lymphocytes with large irregularly shaped nuclei that express the surface marker CD30. There can be significant heterogeneity in clinical manifestation and histological pattern and in rare cases accurate diagnosis can be a challenge. Here, we present an unusual case presentation of cutaneous CD30+ anaplastic large cell lymphoma with significant granulomatous histology pattern that mimicked sarcoid. After a lack of durable response to treatments that included glucocorticoid and methotrexate, targeted treatment with anti-CD30 monoclonal antibody drug conjugate (brentuximab vedotin) yielded long-term clinical remission.

Hemophagocytic lymphohistiocytosis in adults.

Hemophagocytic lymphohistiocytosis (HLH) is an underrecognized disorder due to the variability of its presentation and the fact that in adults, its diagnosis is based on cumbersome, pediatric-based criteria. Data regarding demographics, underlying causes, clinical features, laboratory results, complications, treatments received, and clinical outcomes were collected and analyzed in 41 patients who were diagnosed and treated at University of Arkansas for Medical Sciences between 2007 and 2019. In this group, 51% were male, the median age at diagnosis was 47 years, and 85% (35/41) met the HLH-2004 diagnostic criteria (5/8 variables). When evaluating seven extended variables easily obtained by routine laboratory test, 93% (38/41) of patients met 8 out of 15 criteria. The overall mortality in our patient population was 54% (22/41). The 30-day and 1-year overall survival estimates were 0.73 (95% confidence interval 0.56, 0.84) and 0.46 (95% confidence interval 0.29, 0.62), respectively. Thirty-five patients (85.4%) received HLH-directed therapy, and 19 patients (46.3%) achieved remission. The most common regimen for treating HLH was dexamethasone plus etoposide (53.7%). The patients with malignancy-related HLH had a worse prognosis than those without underlying malignancy, with a 73.33% (11/15) vs 34.62% (9/26) mortality (P = 0.02). In conclusion, despite increasing recognition, HLH remains an enigmatic disorder with increased mortality, even more so with malignancy-associated HLH.

Nivolumab-induced immune-mediated neurotoxicity in Hodgkin lymphoma.

Nivolumab, a monoclonal antibody against programmed cell death-1 used to treat multiple cancers, has fewer side effects than traditional chemotherapy but has displayed a propensity to cause a host of immune-related adverse events. We describe a case of nivolumab immune-mediated neurotoxicity in a 42-year-old Hispanic man with relapsed Hodgkin lymphoma who presented with unilateral facial droop, dysarthria, and dysphagia 1 week after receiving nivolumab. His symptoms rapidly improved with steroids, intravenous immunoglobulin, and infliximab.

Acquired hemophilia A.

Acquired inhibitors of coagulation are a group of rare but potentially life-threatening blood disorders characterized by the presence of autoantibodies directed against clotting factor. Autoantibody against factor VIII is the most common form of clotting factor inhibitor, a condition also known as acquired hemophilia A. We present a clinical series of nine patients diagnosed and treated for acquired hemophilia A at our institution. Among these nine patients, there were five men and four women with a median age of 64 years. All patients presented with bleeding diathesis. Factor eight inhibitor bypassing agent and/or recombinant factor VIIa were predominantly used for control of active bleeding. For elimination of autoantibodies, either steroids alone or the combination of steroids with rituximab or oral cyclophosphamide was used. Despite aggressive measures, two of the patients had a poor outcome; seven of the nine patients (77%) had a good clinical outcome. Acquired hemophilia A should be strongly suspected in any patient presenting with bleeding and a prolonged activated partial thromboplastin time. Early initiation of factor bypassing agents such as activated prothrombin complex concentrates or recombinant factor VIIa, along with the use of immunosuppressive agents, can be lifesaving.

Vitamin B12 deficiency mimicking acute leukemia.

Vitamin B12 deficiency can cause extensive hematologic alterations such as pancytopenia, macrocytosis, hypersegmentation of neutrophils, and hypercellular bone marrow with blastic differentiation. These dysplastic changes can sometimes be so profound that they mimic myelodysplastic syndromes or even acute leukemia, leading to extensive workup and aggressive treatment measures. We present a patient who was referred to our tertiary care medical center for treatment of suspected acute myeloid leukemia on the basis of peripheral smear and bone marrow biopsy findings, and induction chemotherapy was considered. However, the patient was found to have vitamin B12 deficiency, with improvement in pancytopenia and blastic changes with parenteral vitamin B12 supplementation. This highlights the importance of recognizing that dysplastic changes in patients with vitamin B12 deficiency could be misleading.

Diarrhea-associated Hemolytic Uremic Syndrome in Adults: Two Case Reports and Review of the Literature.

Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy syndrome (TMA) defined as a triad of non-immune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin (Stx) or diarrhea-associated HUS is one of the major categories of secondary HUS, which is seen predominantly in children and is regarded as a rare entity in the adult population. We present two cases of sporadic Stx or diarrhea-associated HUS in adult females. Our first case is a 74-year-old Caucasian woman who presented to the emergency department with nausea, vomiting, and bloody diarrhea for five days. The patient reported a history of consuming meatloaf from a local store three days prior to the onset of symptoms. On presentation, laboratory workup was consistent with hemolytic anemia, thrombocytopenia, and acute kidney injury. Thrombocytopenic purpura was ruled out with normal ADAMTS13 activity. The patient's kidney function improved and the platelet count recovered to normal with supportive measures and did not require renal replacement therapy. In the second case, we describe a 79-year-old Caucasian woman with a history of metastatic lung cancer who presented with abdominal pain, nausea, vomiting, and bloody diarrhea. History was positive for consuming meat from a local restaurant a day prior to the onset of symptoms. Initial laboratory work showed severe thrombocytopenia, microangiopathic hemolytic process, and acute kidney injury requiring continuous renal replacement therapy. Due to the unfavorable prognosis of her metastatic lung cancer, the patient and the family members decided to opt for hospice care and she was subsequently transferred to the inpatient hospice. Diarrhea-associated HUS or Stx-HUS is a relatively underreported entity among the adult population. The treatment of typical or Stx-HUS is mainly supportive, but it is critical to rule out other causes of TMAs, especially thrombotic thrombocytopenic purpura (TTP), as it is a medical emergency that requires prompt plasmapheresis.

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.

An unusual presentation of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a B-cell lymphocytic neoplasm with indolent clinical course. If identified early, observation is opted. Many variables lead to the initiation of treatment. Authors describe a 62-year-old male presenting with shortness of breath and found to have white cell count of 1360 × 109/L and subsequently was diagnosed with CLL/SLL. The patient received leukapheresis along with tumor lysis treatment and systemic chemotherapy with fludarabine, cyclophosphamide, and rituximab regimen. His course was complicated with deep venous thrombosis, extensive cutaneous, and sinus mucosa involvement by CLL/SLL. The patient clinically improved and on follow-up clinic visits documented normalization of his white cell counts. The case report brings up a rare presentation of CLL/SLL with such an extreme high white cell count, leukostasis symptoms and extramedullary involvement of disease and encourages providers to be vigilant of rare presentation of CLL/SLL.

Cytomegalovirus appendicitis after hematopoietic stem cell transplantation.

We present the case of a young man with acute lymphoblastic leukemia who developed cytomegalovirus (CMV) appendicitis after receiving alemtuzumab for acute refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT). CMV appendicitis is a rare complication; and we are reporting the first case to our knowledge of CMV appendicitis following HSCT. Our case highlights the importance of recognition of CMV viral reactivation following the use of alemtuzumab. Using a preemptive strategy of checking CMV PCR, with initiation of early effective treatment on detection of CMV replication, may be appropriate following use of alemtuzumab in hematologic malignancies in patients after HSCT.

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.

Correction: Spectrum of Cerebrovascular Disease in Patients with Multiple Myeloma Undergoing Chemotherapy-Results of a Case Control Study.

[This corrects the article DOI: 10.1371/journal.pone.0166627.].

Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management.

Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.

Addressing Opioid-Associated Constipation Using Quality Oncology Practice Initiative Scores and Plan-Do-Study-Act Cycles.

Using the Quality Oncology Practice Initiative, an affiliate program of ASCO, we outlined opioid-associated constipation (OAC) as a subject in need of quality improvement (QI) in our fellowship program at the University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System. We initiated a fellow-led QI project to advance the quality of patient care and provide a valuable avenue for QI training of young physicians. Fellows organized meetings with all stakeholders, addressed the scope of the problem, and devised strategies for OAC management. Monthly meetings were organized using Plan-Do-Study-Act principles. Mandatory check boxes were inserted into our electronic medical record templates to remind all physicians to identify patients on opioid medications and assess and address OAC. Final chart audit and patient satisfaction surveys were performed 6 months after project initiation. Assessment of OAC improved from 52% at baseline to 92% ( P < .003). This improvement corresponded with high patient satisfaction scores, with 90% of surveyed patients reporting adequate management of their constipation. In this QI initiative, we showed that participation in ASCO's Quality Oncology Practice Initiative helps identify areas in need of QI, and such fellow-led QI projects can serve as models for QI training of young physicians.

Chronic Lymphocytic Leukemia with Translocation (2;14)(p16;q32): A Case Report and Review of the Literature.

We report the case of a young African American male with no significant past medical history presenting with low back and bilateral leg pain; presenting CBC and chemistries revealed elevated white blood cell count of 250,000, with anemia (Hb 6.8 g/dL) and thrombocytopenia (platelets 9 K/µL), and elevated LDH, 1008. Physical examination findings were notable for diffuse lymphadenopathy and lower extremity skin nodules. Interestingly the bone marrow biopsy revealed involvement by CLL/SLL with translocation (2;14)(p16;q32) and trisomy 12. The patient was treated with fludarabine-based chemotherapy and steroids for CLL-related ITP with excellent response. After three cycles of chemotherapy, all the enlarged lymph nodes and skin nodules disappeared, and patient had achieved complete hematologic response. In this paper we also reviewed the available literature of CLL patients with translocation (2;14).

Diffuse large B-cell lymphoma of the colon--a rare presentation.

Patients with diffuse large B-cell lymphoma (DLBCL) can present with nodal or extra-nodal disease. The most common extra-nodal site is the gastrointestinal tract, including the stomach or illeo-cecal region. Primary colonic diffuse large B-cell lymphoma (DLBCL) is uncommon and presents a unique diagnostic and therapeutic challenge. We present a case of a middle-aged man who presented with abdominal pain and pathological weight loss and underwent hemi-colectomy for suspected adenocarcinoma. Final pathology revealed DLBCL, completely changing the prognosis and subsequent management. We will discuss some of the aspects of this rare presentation and shed light on therapeutic strategies currently available.