How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists.

The most common forms of B-cell malignancy, non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), have seen a drastic shift in the treatment landscape over the last two decades with the introduction of targeted agents. Among them are Bruton's tyrosine kinase (BTK) inhibitors, which have demonstrated excellent efficacy in indolent B-cell NHLs and CLL. Although BTK inhibitors are generally thought to be more tolerable than chemoimmunotherapy, they are associated with a unique safety profile including varying rates of rash, diarrhea, musculoskeletal events, cardiovascular events, and bleeding. Ibrutinib was the first BTK inhibitor to gain a Health Canada indication, followed by second-generation BTK inhibitors acalabrutinib and zanubrutinib, which have better safety profiles compared to ibrutinib, likely due to their improved selectivity for BTK. As BTK inhibitors are oral agents given continuously until disease progression, long-term adverse event (AE) monitoring and management as well as polypharmacy considerations are important for maintaining patient quality of life. This paper intends to serve as a reference for Canadian nurses and pharmacists on dosing, co-administration, and AE management strategies when caring for patients with indolent B-cell NHL or CLL being treated with BTK inhibitors.

Risk factors for intracranial hemorrhage in adults with acute leukemia.

BACKGROUND: Intracranial hemorrhage (ICH) is a rare, but serious complication in patients with acute leukemia. Little is known about why some patients experience serious bleeding, including ICH, while others do not. MATERIALS AND METHODS: Adults between 18 and 80 years old with acute leukemia and ICH between January 1, 2009 and December 31, 2016 were included. Matched controls were identified using the propensity score matching method. Clinical and laboratory characteristics and outcome data were collected to identify variables associated with ICH. RESULTS: Of 2578 patients diagnosed with acute leukemia during the study period, 55 cases and 161 matched controls were included. Patients who experienced ICH were older (62 vs. 55 years, p = .004) and more likely to have diabetes mellitus (p = .04). Patients with ICH had a higher baseline white blood cell count (mean 84.5 ± 115.8 vs. 28.7 ± 58.5 × 109 /L, p = .001), peripheral blast count (61.3 ± 96.5 vs. 21.2 ± 50.8 × 109 /L, p = .004), and a longer PT (16.5 ± 2.06 vs. 15.3 ± 3.2 s, p = .002). Neither the platelet count at diagnosis, the platelet nadir, the number of days with a platelet count of less than 10 × 109 /L, or a diagnosis of platelet refractoriness were associated with ICH. CONCLUSIONS: Older age and more proliferative disease appear to be associated with ICH, whereas thrombocytopenia alone does not. In patients with newly diagnosed acute leukemia, aggressive cytoreduction in those with leukocytosis may help mitigate the risk of ICH.

Evaluation of Lymphadenopathy and Suspected Lymphoma in a Lymphoma Rapid Diagnosis Clinic.

PURPOSE: Lymphomas often present a diagnostic challenge, and for some a delay in diagnosis can negatively influence outcomes of therapy. We established a nurse practitioner-led lymphoma rapid diagnosis clinic (LRDC) with the goal of reducing wait times to definitive diagnosis. We examined the initial 30-month experience of the LRDC, and results were compared with time periods before implementation of the clinic to determine program impact. METHODS: All patients referred to LRDC with suspicion of lymphoma from June 1, 2015 to Nov 30, 2017 were evaluated. Time from initial consultation to diagnosis was compared with patients diagnosed at our center with lymphoma in 2008 and 2012. Patient symptoms and relevant laboratory/imaging findings were collected to identify patterns of presentation and predictive factors for benign diagnoses. RESULTS: Of the 126 patients evaluated, 66 (52%) had confirmation of lymphoma diagnosis. Median time to lymphoma diagnosis was 16 days for patients assessed in LRDC and 28 days for historical controls (P < .001). By univariable analysis, lymph node size greater than 3.4 cm and presence of mediastinal or abdominal adenopathy increased the likelihood of a diagnosis of malignancy, whereas younger age, being a nonsmoker, and prior rheumatologic condition were associated with a nonmalignant diagnosis. In multivariable analysis, lymph node size, age, and prior rheumatologic diagnosis remained significant. CONCLUSION: Establishing a nurse practitioner-led LRDC was effective in shortening time to diagnosis of lymphoma. Younger age, smaller lymph node size, and prior rheumatologic disorder reduced the likelihood of a cancer diagnosis in our patient population.

Clinical outcomes and transfusion management following intracranial hemorrhage in patients with acute leukemia.

BACKGROUND: There is little evidence to guide management of patients with acute leukemia and intracranial hemorrhage (ICH). Predictors of long-term outcome following ICH are unknown. STUDY DESIGN AND METHODS: This study included adult patients with acute leukemia and ICH over an 8-year period. The primary outcome was data regarding 90-day mortality. Secondary outcomes included data related to the proportion of patients receiving post-remission therapy and predictors of 90-day mortality. RESULTS: ICH occurred in 101 patients; 12 patients died within 72 hours. For the 89 others, 90-day mortality was 40%. Of 43 patients who received induction, 30 achieved remission and 26 received post-remission therapy. Older age (p = 0.03) and higher white count (p = 0.02) at the time of ICH were predictive of inferior survival. During 90-day follow-up, median platelet count was 37 x 109 /L (0-1526 x 109 /L). Lower platelet count during follow-up was predictive of 90-day mortality (p = <0.01). Twenty-one percent of platelet transfusions were provided when the platelet count was less than 10 x 109 /L, 54% between 10 and 29 x 109 /L, and 25% greater than 30 x 109 /L. New or progressive ICH occurred in 23 patients. There was no difference in the median platelet transfusion trigger between patients who had new or progressive ICH and those who did not. CONCLUSION: In patients with acute leukemia, survival following ICH is poor. Older age and higher white count is associated with increased mortality, perhaps reflecting higher risk disease. Following ICH in acute leukemia platelet transfusions do not appear to alter the risk of progressive bleeding or mortality.

Sharing post-AML consolidation supportive therapy with local centers reduces patient travel burden without compromising outcomes.

Acute myeloid leukemia (AML) is frequently treated with induction and consolidation chemotherapy. Consolidation chemotherapy can be delivered on an ambulatory basis, requiring some patients to travel long distances for treatment at specialized centers. We developed a shared care model where patients receive consolidation chemotherapy at a quaternary center, but post-consolidation supportive care at local hospitals. To evaluate the impact of our model on patient travel and outcomes we conducted a retrospective analysis of AML and acute promyelocytic leukemia patients receiving consolidation over four years at our quaternary center. 73 patients received post-consolidation care locally, and 344 at the quaternary center. Gender, age and cytogenetic risk did not significantly differ between groups. Shared care patients saved mean round trip distance of 146.5km±99.6 and time of 96.7min±63.4 compared to travelling to quaternary center. There was no significant difference in overall survival between groups, and no increased hazard of death for shared care patients. 30, 60, and 90day survival from start of consolidation was 98.6%, 97.2%, and 95.9% for shared care and 98.8%, 97.1%, and 95.3% for quaternary center patients. Thus, a model utilizing regional partnerships for AML post-consolidation care reduces travel burden while maintaining safety.

Feasibility of outpatient consolidation chemotherapy in older versus younger patients with acute myeloid leukemia.

Intensive consolidation chemotherapy for acute myeloid leukemia (AML) patients in complete remission is being increasingly administered on an outpatient basis. Although this approach has been found to be safe and feasible in younger patients, its safety in older patients remains unknown. We therefore undertook an evaluation of outpatient-based consolidation chemotherapy in older AML patients, and compared results to younger patients treated at the same institution over the same time period. The overall rate of readmission was ~50%, mostly for infections, with mean admission duration of 2 weeks. The overall mortality rate was 2.2%. Readmission rates and duration of readmission were somewhat higher in older patients, but infection rate, intensive care (ICU) admissions, and mortality rates were comparable to those in the younger patient cohort. However, we also observed that rates of febrile neutropenia, bacteremia, ICU admission, and death were significantly higher during the second consolidation, as compared with the first, in both younger and older patients. We conclude that outpatient-based consolidation therapy can be safely undertaken in a substantial proportion of fit older patients with AML.

Counselling and adverse event management for patients with myelodysplastic syndromes undergoing azacitidine therapy: a practice standard for Canadian nurses.

Azacitidine (5-azacytidine, VIDAZA) is a disease-modifying agent that improves survival, reduces transfusion dependence, and reduces progression to acute myeloid leukemia in patients with higher risk myelodysplastic syndromes. Azacitidine injection is associated with characteristic adverse events (AEs) that must be managed in order for patients to stay on therapy and achieve optimal therapeutic outcomes. These AEs include injection-site reactions, cytopenias, and gastrointestinal effects. Oncology nurses are uniquely positioned to provide patient support and counselling, thereby helping patients and their families set clear expectations for azacitidine therapy. This article presents a nursing standard designed to support Canadian oncology nurses in the key areas of counselling for patients initiating and continuing azacitidine, as well as nursing strategies for prevention and management of azacitidine-associated AEs. Many of the general principles discussed in this nursing standard can be applied broadly to many diseases and treatments.