Severe first infusion reaction related to cetuximab in cancer patients in Arkansas.

INTRODUCTION: Cetuximab, a chimeric monoclonal antibody, is a commonly used anticancer drug that prevents binding of epidermal growth factor to epidermal growth factor receptor. It has been widely used in a variety of cancers since its initial approval by the FDA in 2004. Despite its efficacy, it has met with some genuine concerns especially regarding the anaphylactoid reactions occurring after first infusions. Cetuximab-related first infusion reaction has been found to be much more prevalent in the Southeastern United States with several studies from the southern United States supporting it. The purpose of our study was to determine the rate of first infusion reaction in the state of Arkansas and the factors that could predispose to first infusion reaction. METHODS AND RESULTS: We performed a retrospective chart review of consecutive patients who received cetuximab between January 2004 and December 2016 at the University of Arkansas for Medical Sciences. We included a total of 220 patients in our analysis out of which 32 (14.5%) developed cetuximab-related first infusion reaction. There was a statistically significant increased risk in males versus females (18.2% vs. 8.4%, P = 0.045) and trend toward significance for the difference between Caucasians and Blacks (16.5% vs. 7.1%, P = 0.054). CONCLUSION: There is increased incidence of cetuximab-related first infusion reaction in Arkansas which is much higher than the national average but comparable to the incidence in other neighboring states in the Southeastern United States. This increased incidence tends to cluster in Caucasian males. Safer alternatives should be preferred for treatment of cancers particularly in the Southeastern United States whenever possible.

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma.

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next-generation flow cytometry (sensitivity of 10-5 cells) at 3- to 6-month intervals. With a median follow-up of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, whereas 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95% vs 84%; P = .001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 years (range, 0-4.9). However, 27% of MRD conversion-positive patients had not yet experienced a clinical relapse, with a median follow-up of 9.3 years (range, 2.2-21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared with patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

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.

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.

Acquired Amegakaryocytic Thrombocytopenia Misdiagnosed as Immune Thrombocytopenia: A Case Report.

INTRODUCTION: Acquired amegakaryocytic thrombocytopenia (AATP) is a rare bleeding disorder that causes severe thrombocytopenia with preserved hematopoiesis of other cell lineages. Many cases are misdiagnosed and treated as immune thrombocytopenia. CASE PRESENTATION: We report a case of AATP, in a 50-year-old man, that was treated as immune thrombocytopenia for years with no clinical response. The disorder later was diagnosed as AATP after bone marrow biopsy and was successfully treated with cyclosporine. DISCUSSION: The exact mechanism of AATP remains unclear; it is suspected to be an immune-mediated process. Patients with AATP present with severe bleeding and thrombocytopenia, which is usually unresponsive to high-dose corticosteroids. There are no standard treatment guidelines for AATP. Cyclosporine and antithymocyte globulin are found to be effective in some cases. The prompt diagnosis of AATP is vital because it carries high mortality because of excessive bleeding, and it can progress into aplastic anemia or myelodysplastic syndrome.

Immunotherapy Outcomes in Advanced Melanoma in Relation to Age.

INTRODUCTION: Older age is a melanoma risk factor. Elderly individuals are likelier to have immunosenescence, which could help melanoma cells escape immune surveillance. Hence, it is believed that elderly people cannot mount a potent immune response to checkpoint inhibitors to eliminate melanoma. OBJECTIVES: To investigate age-related differences in the time to progression, overall survival, and immunotherapy-related adverse events among patients with metastatic melanoma who received checkpoint inhibitors. METHODS: We retrospectively identified patients at our institution between January 2012 and December 2016 with stage IV melanoma who received at least 1 dose of ipilimumab, pembrolizumab, nivolumab, or combined ipilimumab and nivolumab. Demographic, pathologic, and clinical characteristics were obtained. Immune-related response criteria were used to define responses. RESULTS: Twenty-nine patients were younger than age 65 years and 31 were age 65 years or older. Time to progression was comparable between the age groups (hazard ratio = 0.79, 95% confidence interval = 0.37-1.70, p = 0.46). Overall survival was not significantly different after immunotherapy between groups (hazard ratio = 0.75, 95% confidence interval = 0.31-1.82, p = 0.491). Overall, immunotherapy-related adverse events were comparable between groups, with 62% in younger patients (18/29) and 45% in older patients (14/31 p = 0.19). Of 60 patients, 30 responded to immunotherapy. Nonresponders were more likely than responders to have BRAF-mutated melanomas (16 [53.3%] vs 8 [27.6%]; p = 0.04) and less likely to have immunotherapy-related adverse events (12 [40%] vs 20 [66.7%]; p = 0.04). CONCLUSION: Aging does not seem to affect response to checkpoint inhibitors. Elderly patients with metastatic melanoma should be treated similarly to younger patients.

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.

Late breast cancer recurrence with bone marrow metastases and acute pulmonary hypertension.

Bone marrow is one of the most common sites of metastasis from breast cancer. Micrometastases to the bone marrow usually evade the systemic therapies used for the treatment of cancer and eventually lead to relapse later in the course of the illness. We report here a unique case of parallel progression of these bone marrow metastases in a patient with breast cancer who had a relapse a few years after treatment of her primary breast cancer, and she presented with diffuse marrow involvement and pulmonary hypertension without any definitive metastases elsewhere.

Pembrolizumab-Induced Pancytopenia: A Case Report.

INTRODUCTION: Programmed death receptor-1 blockade with pembrolizumab is approved by the US Food and Drug Administration to treat patients with metastatic melanoma. Activating T cells to fight cancer may cause immune-mediated adverse events. Pembrolizumab-induced pancytopenia has not been previously reported in the medical literature, to our knowledge. CASE PRESENTATION: A 52-year-old Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced multiple adverse events along her course of therapy with pembrolizumab, ranging from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia after the 18th cycle of pembrolizumab. Severe pancytopenia improved after high-dose corticosteroids and a 5-day course of intravenous immunoglobulin therapy. DISCUSSION: In our case, pembrolizumab-induced Grade 4 pancytopenia resolved via a combination of corticosteroids and intravenous immunoglobulins. Pancytopenia reached a nadir in 10 weeks, and it took 16 weeks for meaningful recovery.

Well-Differentiated Neuroendocrine Tumor-A Low b-Grade Tumor's Aggressive Course and Dismal Outcome: A Case Report.

INTRODUCTION: Incidence of well-differentiated neuroendocrine tumors (NETs) of the colon and rectum is increasing and is now approximately 1 per 100,000 in the US. NETs are either well-differentiated (indolent) or poorly differentiated (aggressive). The majority of these tumors are found incidentally during screening colonoscopies and rarely are associated with symptoms of hormonal syndrome, even during the advanced stage. Metastatic well-differentiated NETs of the colon and rectum are incurable, hard to treat, and associated with a poor prognosis and survival rates similar to colorectal adenocarcinoma survival. CASE PRESENTATION: A 56-year-old man presented to our clinic with right-sided weakness and a 40-pound weight loss during the previous 2 months. A neurologic examination was remarkable for atrophy of the right trapezius muscle and decreased strength in the right upper extremity. Imaging revealed extensive blastic and lytic lesions involving the axial skeleton, a large rectal mass, a large necrotic nodal mass extending from the left iliac region to the level of the left renal veins, and multiple necrotic liver metastasis. Liver lesion fine-needle aspiration findings were consistent with metastatic well-differentiated neuroendocrine carcinoma. DISCUSSION: This case illustrates how a low-grade tumor can have an aggressive course with poor outcomes. Metastatic well-differentiated NETs of the colon and rectum remain difficult to treat because evidence is scarce. More research is needed on this topic.

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.

Successful Management of Neobladder Variceal Bleeding.

Hematuria from a neobladder can occur due to a variety of pathologies including tumors, stones, and fistulas. Variceal bleeding in a neobladder is a very rare condition with only one case reported in literature. We present a case of a patient with cirrhosis and portal hypertension and an ileocolic orthotopic neobladder presenting with hematuria. Computed tomographic angiography showed dilated varices around the neobladder which were successfully embolized. To the best of our knowledge, this is the first report case of variceal bleeding in a neobladder successfully managed with the combination of TIPS (transjugular intrahepatic portosystemic shunt) procedure and embolization.