Case Report: ASCENIV use in three young children with immune abnormalities and acute respiratory failure secondary to RSV infection.

Respiratory syncytial virus (RSV) is the most common etiology of bronchiolitis in young children. While most children clinically improve with care at home, RSV is the leading cause of hospitalization among infants aged 12 months or less. Common modalities of treatment for children with immune dysregulation include respiratory support and best supportive care, which may include immunoglobulin therapy. All immunoglobulin therapies adhere to Food and Drug Administration (FDA) - established standards for antibodies against measles, polio, and diphtheria, but there are no required standards for problematic respiratory viral pathogens, including RSV and others. ASCENIV is an approved IVIG that is manufactured from blending normal source plasma with plasma from donors that possess high antibody titers against RSV and other respiratory pathogens of concern. ASCENIV was developed, in part, to the unmet need that exists in immunocompromised patients who lack sufficient antibodies against problematic viral pathogens. ASCENIV is not a currently approved treatment for severe RSV and other viral infections. There is a lack of research regarding its potential benefits in the acute treatment period for RSV and in the pediatric population. Therefore, this case series was developed to describe real-world experiences of ASCENIV use in this less well studied clinical scenario. This case series reviews three pediatric patients ≤ 5 years of age with immune dysregulation and who were severely ill with RSV. Despite receiving best supportive care, and standard immunoglobulin therapy for some, the patients' clinical status continued to decline. All patients received ASCENIV in an intensive care setting. Each patient had ultimately recovered due to the various medical interventions done. This case series demonstrated that ASCENIV (500mg/kg) administration may have contributed to the treatment outcomes of a less well studied age-cohort of patients. In addition, no adverse side effects were observed after ASCENIV administration. Further analysis of the benefits of ASCENIV for the acute and preventative treatment in patients younger than 12 years of age with immune dysregulation should continue to be explored.

ASCENIV utilization in a primary immunodeficiency patient with recurrent viral infections.

Primary immunodeficiency (PI) patients may still experience persistent viral and bacterial respiratory infections with ongoing treatments. We report a challenging case of a PI patient who experienced recurrent viral respiratory infections despite receiving standard immunoglobulin replacement therapy. The patient was subsequently managed with immune globulin intravenous, human-slra (ASCENIV™) that contains elevated antibodies against multiple respiratory pathogens. The patient demonstrated significant clinical improvement with a resolution of persistent and debilitating viral respiratory infections and associated sequela.

Rapid infusion rituximab for maintenance therapy: is it feasible?

Rituximab is an anti-CD-20 monoclonal antibody used in the management of lymphoproliferative disorders. The use of maintenance rituximab has improved progression free survival and overall survival in follicular lymphomas. Although rapid rituximab infusions have been studied extensively, there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas. The primary objective of this retrospective analysis was to evaluate the incidence of Grade 3 and 4 toxicities with maintenance rapid infusion rituximab according to the Common Terminology Criteria for Adverse Events version 4 (CTC v. 4). Secondary objectives included evaluating all grade infusion related adverse events and correlation of adverse events with varying schedules of rituximab maintenance therapy. All patients who received rapid infusion rituximab as maintenance therapy for low grade lymphoma between December 2007 and November 2011 were included. Rapid rituximab infusions were administered over 90 minutes. Demographic, laboratory and clinical data were collected. A total of 109 patients received 647 rapid rituximab infusions. Three patients experienced an adverse reaction which resulted in one grade 1 infusion reaction and three grade 3 infusion reactions. No patients required hospitalization. All 3 patients received pharmacological and/or supportive care to relieve symptoms associated with the reaction.

Optimizing premedications in the prevention of bendamustine infusion-related reactions.

BACKGROUND: Bendamustine is indicated for the treatment of chronic lymphocytic leukemia (CLL) and rituximab refractory indolent non-Hodgkin lymphoma. Clinical trials have reported a 25% incidence of infusion-related reactions (IRRs) in patients receiving bendamustine. While these reactions are well documented, there is no consensus on the optimal premedication regimen for the prevention of these adverse effects. At our center, we utilize a regimen of ondansetron 16 mg orally and dexamethasone 10 mg IV push prior to each infusion of bendamustine. This report describes our experience with our current premedication regimen with regard to IRRs and the incidence of febrile neutropenia (FN). METHODS: We retrospectively analyzed 73 consecutive patients receiving bendamustine infusions at our institute from June 2008 to June 2010 to determine the incidence of IRRs and FN. The primary objective was to determine the incidence of IRRs. Secondary objectives included incidence of FN and hospital admission rate. RESULTS: A total of 478 infusions of bendamustine were administered to 73 consecutive patients. The median patient age was 69 years. IRRs affected 19% of our population, and 10.9% experienced FN. Notably, all IRRs were attributed to rituximab infusions and no patients experienced an IRR when receiving bendamustine alone. This compares favorably to the initial reported IRRs of 25% with bendamustine alone. CONCLUSIONS: Based on our experience with bendamustine, ondansetron and dexamethasone provide a safe and effective prevention of IRRs associated with bendamustine. By avoiding the use of other premedications, the likelihood of additional complications or adverse affects can be minimized.

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome.

BACKGROUND: Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline-based induction therapy. METHODS: This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS). RESULTS: The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%-71%), and median OS was 6.5 (95% CI, 3.9-8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04-0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38-13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01). CONCLUSIONS: Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy.

Salvage chemotherapy regimens for acute myeloid leukemia: Is one better? Efficacy comparison between CLAG and MEC regimens.

There is no standard salvage regimen for AML. We retrospectively compared two commonly used regimens at our institution: CLAG and MEC. The complete response rate (CR) was 37.9% for CLAG (n=97) and 23.8% for MEC (n=65) (P=0.048), with median overall survival (OS) of 7.3 and 4.5 months, respectively (P=0.05). In primary refractory disease, CR was 45.5% for CLAG and 22.2% for MEC (P=0.09), with median OS of 11 and 4.5 months, respectively (P=0.07). In first relapse, CR was 36.8% and 25.9% (P=0.35) and median OS was 6.7 and 6.7 months, respectively (P=0.87). Our data support use of CLAG for RR-AML.

Chronic myeloid leukemia therapy: focus on second-generation tyrosine kinase inhibitors.

BACKGROUND: Chronic myeloid leukemia, the most common adult leukemia, is characterized by the Ph+ chromosome produced by the fusion of the BCR gene from chromosome 22 and the ABL gene from chromosome 9. Inhibition of the deleterious effects of this potent oncogene by the tyrosine kinase inhibitor (TKI) imatinib has revolutionized care of this disease, but intolerance and resistance does occur. METHODS: The authors have reviewed both the preclinical and the clinical data concerning second-generation TKIs intended to circumvent or ameliorate issues with imatinib intolerance or resistance. RESULTS: Two second-generation TKIs, dasatinib and nilotinib, are currently approved by the US Food and Drug Administration. Both have shown significant clinical activity in patients with chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) who are resistant or intolerant to imatinib or other therapies. CONCLUSIONS: The TKIs are a superb example of an effective targeted approach for a malignant disease. As more clinical data become available and additional novel agents are developed, specific therapy and dosing strategies for individuals with CML will depend on the status of their disease, the anticipated side effects, and concurrent drug therapy.

Mould breakthrough in immunosuppressed adults receiving anidulafungin: a report of 2 cases.

Anidulafungin is a semi-synthetic echinocandin antifungal agent indicated for treatment of candidemia and invasive candidiasis. In vitro and clinical data indicate activity of anidulafungin toward invasive mould infections, however, clinical data in human subjects is limited. A paucity of data exists regarding breakthrough mould infections in immunocompromised patients receiving anidulafungin. We report on two immunocompromised adult patients undergoing therapy for hematologic malignancies who developed probable breakthrough mould infections while receiving anidulafungin.

Abbreviated rasburicase dosing for the prevention and treatment of hyperuricemia in adults at risk for tumor lysis syndrome.

BACKGROUND: The purpose of this study is to report the experience of using abbreviated rasburicase dosing for adult patients at risk for developing hyperuricemia secondary to tumor lysis syndrome. PATIENTS AND METHODS: All patients who received rasburicase from January 2003 through March 2004 were identified, and a retrospective chart review was conducted. RESULTS: Thirteen patients received >/= 1 dose of rasburicase for the prevention or treatment of hyperuricemia. Of these patients, 8 patients received 1 dose, 3 patients received 2 doses, and 2 patients received 3 doses of rasburicase. All 13 patients experienced normalization of plasma uric acid levels within 24 hours (mean uric acid decreased from 9.1 mg/dL to 0.68 mg/dL). Mean serum creatinine decreased from 2.3 mg/dL to 1.6 mg/dL. No patients required hemodialysis. CONCLUSION: Our experience supports that abbreviated courses of rasburicase are effective in managing hyperuricemia in patients at risk for tumor lysis syndrome.