Incidence of Febrile Neutropenia in Autologous Hematopoietic Stem Cell Transplant (HSCT) Recipients on levofloxacin prophylaxis.

BACKGROUND: Autologous hematopoietic stem cell transplant (HSCT) recipients are not uniformly considered as "high risk" enough to receive fluoroquinolone (FQ) prophylaxis. The risks versus benefits of FQ prophylaxis in autologous HSCT require further investigation. METHODS: A retrospective chart review of patients > 19 years old who received an autologous HSCT at Nebraska Medicine analyzed two time periods (period 1: no prophylaxis [2013-2015] versus period 2: levofloxacin prophylaxis [2015-2016]) to characterize the clinical impact of levofloxacin prophylaxis on autologous HSCT recipients. RESULTS: A total of 224 autologous HSCT were screened with 214 included. Febrile neutropenia (FN) developed in 101/113 (89%) versus 60/101 (59%) patients in the no prophylaxis (NPx) versus prophylaxis (Px) group (P < .01). Time to onset of FN was a median 6 versus 7 days (P = .01), and total bloodstream infections (BSI) were 33/113 (29%) versus 7/101 (7%) (P < .01) in NPx and Px groups, respectively. Gram-negative BSI were absent in the Px group. Viridans group streptococci were the most common Gram-positive BSI overall, with FQ-resistance more common in Px recipients. Rates of Clostridium difficile infections, length of hospital stay, or death at 100 days post-HSCT did not differ between the groups. CONCLUSION: Fluoroquinolone prophylaxis introduced into autologous HSCT care at our institution in 2015 resulted in prevention of Gram-negative BSI, decreased rates of FN, microbiologically documented infections, and a delay in time to onset of FN compared with the prior NPx. FQ prophylaxis in autologous HSCT recipients should be evaluated per individual institution.

Olanzapine as a rescue antiemetic in hematopoietic stem cell transplant.

BACKGROUND: Chemotherapy-induced nausea and vomiting occurs in up to 80% of patients undergoing chemotherapy treatment and is associated with a deterioration in quality of life. Olanzapine is an atypical antipsychotic antagonist blocking a variety of neurotransmitters in the nausea and vomiting pathophysiology. OBJECTIVES: The primary objective of this study is to determine whether olanzapine is associated with improved breakthrough nausea and vomiting in patients undergoing hematopoietic stem cell transplant. Secondary outcomes include number of documented emesis episodes, an evaluation of patient oral intake, and number of rescue antiemetic agents administered after olanzapine initiation. METHODS: This is a retrospective cohort review examining the effects of olanzapine for the treatment of breakthrough nausea and vomiting following hematopoietic stem cell transplant. Patients undergoing autologous or allogeneic hematopoietic stem cell transplant between January 2014 and October 2017 were included. RESULTS: A total of 150 patients were included in the study. Olanzapine use was associated with a complete response in 30% of patients for breakthrough chemotherapy-induced nausea and vomiting (p < 0.0001). An improvement in nausea (p < 0.0001) and vomiting (p = 0.02) was also observed in patients. Olanzapine administration was associated with lower as needed antiemetic usage (p < 0.0001) as well as fewer emesis episodes (p < 0.0001) but had no effect on oral intake (p = 0.13). CONCLUSIONS: Olanzapine was associated with significant improvements in breakthrough nausea and vomiting control while reducing the number of emesis episodes and required antiemetic doses in the hematopoietic stem cell transplant population. Olanzapine may be beneficial in optimizing antiemetic regimens for breakthrough chemotherapy-induced nausea and vomiting control in patients undergoing hematopoietic stem cell transplant.

Brentuximab vedotin desensitization in a patient with refractory Hodgkin's lymphoma.

Brentuximab vedotin has emerged as a useful treatment option for relapsed or refractory Hodgkin's lymphoma; however, uncommon cases of anaphylactic reactions may require its permanent discontinuation. We report a 29-yr-old woman with refractory Hodgkin's lymphoma, who developed an anaphylactic reaction during the second dose of brentuximab vedotin. A 12-step desensitization protocol was followed; after premedicating with antihistaminic agents, methylprednisolone and montelukast, a total dose of 156 mg of brentuximab vedotin (1.8 mg/kg) was given as three infusions with increasing rate and concentration. Such desensitization protocol can allow safe administration of brentuximab vedotin and may have a broader applicability in managing hypersensitivity reactions with other monoclonal antibodies.

Alisertib: a review of pharmacokinetics, efficacy and toxicity in patients with hematologic malignancies and solid tumors.

INTRODUCTION: Aurora kinases are essential mediators in cell mitosis. Amplification of these kinases can lead to the development of malignancy and may be associated with inferior survival. Alisertib is an oral aurora kinase inhibitor which has been shown to induce cell-cycle arrest and apoptosis in preclinical studies. It is currently under investigation for a wide variety of malignancies including hematologic (specifically Non-Hodgkin's lymphoma) and solid tumors. Areas covered: A PubMed search was performed to identify clinical studies reporting outcomes with alisertib. Promising results are notable in patients with peripheral T cell lymphoma in particular, forming the basis for the first phase 3 randomized trial of alisertib. Although it did show encouraging response rates, it failed to demonstrate superiority over the comparator arm at an interim analysis, halting further enrollment. Expert opinion: Despite disappointing early results, alisertib remains under investigation in a number of cancer types both as monotherapy and in combination with traditional cytotoxic chemotherapy, with encouraging results. Most common toxicities in early trials include myelosuppression alopecia, mucositis and fatigue. The relatively manageable toxicity profile of alisertib along with ease of dosing may allow it to be combined with other oral agents or traditional chemotherapy across a wide variety of malignancy types.

Rhabdomyolysis during therapy with daptomycin.

The use of daptomycin has been associated with an elevation in creatine phosphokinase level, with a reported incidence of 2.8% in phase III clinical trials. Published case reports have documented the presence of myopathy in patients who received daptomycin; however, there have been no previously reported cases of rhabdomyolysis in animals or humans to date. We describe a case of rhabdomyolysis during therapy with daptomycin.

Oral targeted therapies: managing drug interactions, enhancing adherence and optimizing medication safety in lymphoma patients.

The advent of newer, targeted oral chemotherapy medications such as small molecule kinase inhibitors, ibrutinib and idelalisib, has created additional options for the treatment of lymphoma. The targeted nature of these agents offers many patient-identified advantages over older, intravenously administered chemotherapy regimens such as ease of self-administration and an increased sense of independence. However, newer oral agents also present unique challenges not previously experienced with older therapies that may affect safety, efficacy and patient adherence. In this article, we review oral agents for the treatment of lymphoma, how to evaluate and manage drug-drug and drug-food interactions with concomitant oral medications, and issues with patient adherence as well as methods to determine adherence for oral chemotherapy.