Idelalisib: Practical Tools for Identifying and Managing Adverse Events in Clinical Practice.

Idelalisib is a first-in-class oral selective inhibitor of phosphatidylinositol 3-kinase delta, which is selectively expressed in hematopoietic cells, where it is critical to B-cell receptor signaling and B-cell development and function. Idelalisib is approved in the United States for the treatment of relapsed chronic lymphocytic leukemia (CLL; in combination with rituximab), relapsed follicular lymphoma (FL), and small lymphocytic lymphoma (SLL) and in the European Union for the treatment of CLL (in combination with rituximab). Approval was based on clinical activity in a phase II trial in indolent non-Hodgkin lymphoma and a phase III trial in CLL. Because idelalisib is a relatively new treatment option for patients with relapsed CLL, SLL, and FL, with a safety profile distinct from other agents, it is important for advanced practitioners (APs) to familiarize themselves with the adverse event (AE) profile and educate their patients as well. As active members of the oncology care team, APs can play a vital role in optimizing outcomes in patients receiving idelalisib therapy. This review will familiarize APs with the AE profile of idelalisib and provide practical information about the identification and management of AEs associated with idelalisib therapy.

Blood pressure and renal function after kidney donation from hypertensive living donors.

BACKGROUND: Rising numbers of patients reaching end-stage kidney disease intensify the demand for expansion of the living-kidney-donor pool. On the basis of low risk in white donors with essential hypertension, our transplant center undertook a structured program of accepting hypertensive donors if kidney function and urine protein were normal. This study reports outcomes of hypertensive donors 1 year after kidney donation. METHODS: We studied detailed measurements of blood pressure (oscillometric, hypertensive therapy nurse [RN], and ambulatory blood pressure monitoring [ABPM]), clinical, and renal characteristics (iothalamate glomerular filtration rate [GFR], urine protein, and microalbumin) in 148 living kidney donors before and 6 to 12 months after nephrectomy. Twenty-four were hypertensive (awake ABPM>135/85 mm Hg and clinic/RN BP>140/90 mm Hg) before donation. RESULTS: After 282 days, normotensive donors had no change in awake ABPM pressure (pre 121 +/- 1/75 +/- 2 vs. post 120 +/- 1/ 5 +/- 1 mm Hg), whereas BP in hypertensive donors fell with both nonpharmacologic and drug therapy (pre 142 +/- 3/85 +/- 2 to post 132 +/- 2/80 +/- 1 mm Hg, P<.01). Hypertensive donors were older (53.4 vs. 41.4 years, P<.001) and had lower GFR after kidney donation (61 +/- 2 vs. 68 +/- 1 mL/min/1.73m, P<.01). After correction for age, no independent BP effect was evident for predicting GFR either before or after nephrectomy. Urine protein and microalbumin did not change in either group after donor nephrectomy. CONCLUSIONS: Our results indicate that white subjects with moderate, essential hypertension and normal kidney function have no adverse effects regarding blood pressure, GFR, or urinary protein excretion during the first year after living kidney donation. Although further studies are essential to confirm long-term safety, these data suggest that selected hypertensive patients may be accepted for living kidney donation.

Clinical staging and prognostic markers in chronic lymphocytic leukemia.

In this article we provide a brief review of the two staging systems in chronic lymphocytic leukemia, and we discuss the more recently identified, new prognostic markers that are of interest to clinicians and researchers in this field.

Alemtuzumab maintenance may safely prolong chemotherapy-free intervals in chronic lymphocytic leukemia.

This prospective, single-arm study utilized alemtuzumab as a single agent in a novel maintenance schedule in previously treated chronic lymphocytic leukemia patients with the goal of delaying progression of disease and requirement for chemotherapy. In previously treated CLL patients who had achieved stable disease or better, the following schedule of subcutaneous alemtuzumab was administered: a dose escalation in the first week (3, 10 and 30 mg), followed by 7 weeks of 30 mg alemtuzumab once weekly, 16 weeks of 30 mg once every 2 weeks, followed by once every 3 weeks for 24 weeks. Thus, the entire duration of the planned treatment was 48 weeks. A total of 12 patients were enrolled 11 of which had at least one marker of poor prognosis (unmutated, Zap 70+, CD38+, del11q and del17p). The median chemotherapy-free interval was 13 months, and the median time to disease progression was 10 months. Three patients achieved a CR, one achieved nPR, one had a PR, five failed and two had shown a beneficial response but because of recurrent ITP had to stop alemtuzumab. In six of the 10 patients with previously relapsed disease, the chemotherapy-free interval was longer than their prior chemotherapy-free period. One patient had a reactivation of CMV antigenemia, and another had a bacterial pneumonia. There were no grade 3 or 4 toxicities. Alemtuzumab used in a maintenance schedule is a potentially safe and useful tool in delaying disease progression and chemotherapy-free intervals in previously treated CLL patients.

A combination of rituximab, cyclophosphamide and dexamethasone effectively treats immune cytopenias of chronic lymphocytic leukemia.

Auto-immune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) are known complications of chronic lymphocytic leukemia (CLL). Rituximab, cyclophosphamide and dexamethasone (RCD) effectively target lymphocytes and inhibit autoimmune processes. We reviewed 21 patients with CLL treated for AIHA alone (n = 18), ITP alone (n = 1) or both (n = 2) with the following RCD regimen: rituximab 375 mg/m(2) i.v. infusion given on day 1, cyclophosphamide 750-1000 mg/m(2) i.v. on day 2 and dexamethasone 12 mg day 1-7 given every 3 weeks. Response to treatment was seen in all 20 patients with CLL with AIHA. Median hemoglobin pre-treatment was 8 g/dL. The median change in hemoglobin was 5.2 g/dL and the median post-treatment hemoglobin level was noted to be 13.1 g/dL. Median duration of response was 22 months. Nine relapsed patients responded as well. Fifty percent of evaluable patients converted to Coombs negative with median duration of response of 41 months vs. 10 months for those who did not convert. This difference was not statistically significant (p = 0.0674). Steroid-refractory immune thrombocytopenia was present in three patients and all responded to RCD. There were no hospitalisations or infections directly related to RCD. RCD is a safe and effective regimen in the treatment of immune cytopenias associated with CLL.