Expert consensus guidelines for the prophylaxis and management of tumor lysis syndrome in the United States: Results of a modified Delphi panel.

INTRODUCTION: Tumor lysis syndrome (TLS), which occurs spontaneously or in response to anticancer treatment, results in the release of intracellular potassium, phosphorus, and nucleic acids into the bloodstream, which results in secondary clinical complications that may be fatal. Prior TLS guidelines do not take into consideration potent novel oncologic agents or contemporary treatment paradigms with increased risk of TLS. Thus, a modified Delphi panel of experts was convened to provide an update for TLS management guidelines based upon a combination of supporting literature and practice consensus. METHODS: A three-round modified Delphi process was implemented. For round 1, nine expert panelists completed a web-based questionnaire developed using published literature. In round 2, panelists were asked to reconsider their answers to questions that did not reach consensus (defined as ≥ 66% agreement among voting panelists). Round 3 was an unblinded, moderated virtual meeting to discuss any remaining questions that did not reach consensus. RESULTS: Detailed recommendations are given for prophylaxis, monitoring, and management of TLS risks and complications, with hydration being a key element of TLS prophylaxis and management. Guidelines for the management of acute effects of TLS and prevention of long-term renal effects include management of hyperkalemia, hypocalcemia, hyperphosphatemia, and hyperuricemia. DISCUSSION: Although the control of uric acid levels is quite effective with currently available agents, panelists emphasize the importance of monitoring and treating other dangerous electrolyte abnormalities such as hyperkalemia and hyperphosphatemia. Guidelines from this modified Delphi panel should aid clinicians in preventing and managing TLS.

Evaluation of Clinical Pharmacy Services for Phase 1 Clinical Trials.

BACKGROUND: Phase 1 clinical trials have challenges relative to later-phase clinical trials. As of April 2020, there were 71 active phase 1 cancer clinical trials at the Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center (SKCCC), and limited clinical pharmacy services are dedicated to the unique needs of phase 1 clinical trials. OBJECTIVES: To characterize the current phase 1 cancer-specific clinical pharmacy services at National Cancer Institute (NCI)-designated institutions, and to develop a framework for the implementation of these services at Johns Hopkins Medicine SKCCC. METHODS: We queried the current pharmacy practices for phase 1 cancer clinical trials at NCI-designated institutions through an e-mailed 20-question national online survey to 208 pharmacists. The recipients were asked to rate how often specific pharmacy services were performed, using a 4-point Likert scale of rarely/never (<10%), sometimes (10%-49%), often (50%-80%), or almost always (>80%). The services were grouped into pretrial implementation support, phase 1 trial implementation support, medication profile review, medication therapy management, and miscellaneous support. Using the survey results, a framework for phase 1 trial clinical pharmacy services was developed concurrently to prioritize protocol complexity, monitoring requirements, and clinical pharmacy interventions. RESULTS: Of the 208 surveys e-mailed, 45 recipients responded, for an overall survey response rate of 22%. The responses were divided into 2 subgroups for the institutions that currently conduct phase 1 cancer clinical trials, including institutions with >40 active phase 1 cancer clinical trials and institutions with ≤40 active phase 1 cancer clinical trials. The institutions with >40 active phase 1 cancer clinical trials were more likely to have pharmacists involved with direct participant care (47% vs 18.8%, respectively) and document medication lists for phase 1 trial participants (41% vs 18.8%, respectively) than institutions with ≤40 active phase 1 cancer clinical trials. The survey results assisted in developing a framework to classify drug regimens as platinum level (ie, higher complexity) or standard level (ie, lower or average complexity) to prioritize clinical pharmacy services based on their complexity level. CONCLUSION: Our analysis of current phase 1 clinical trial pharmacy practices at NCI institutions enabled the development of a framework for increased collaboration with research teams and phase 1 clinical trial-specific clinical pharmacy services within Johns Hopkins Medicine SKCCC.

Advanced Practice Perspectives on Preventing and Managing Tumor Lysis Syndrome and Neutropenia in Chronic Lymphocytic Leukemia.

Tumor lysis syndrome (TLS) and neutropenia are significant toxicities in the treatment of chronic lymphocytic leukemia (CLL). Both TLS and neutropenia can lead to potentially life-threatening complications for patients with chronic lymphocytic leukemia undergoing antineoplastic therapy. This article focuses on diligent risk assessment, prophylaxis, early identification, monitoring, patient education, and prompt intervention for TLS and neutropenia. These are all necessary steps to reduce life-threatening complications. Guidelines are available for risk assessments for both TLS and neutropenia. Once risk is established, prophylaxis and monitoring recommendations can be found in available guidelines. There are no established guidelines or widely used decision-making standards for the treatment of clinical TLS. General management strategies are well documented in the literature, with some degree of customization to each individual patient. If fever occurs in the setting of neutropenia, there are well-established guidelines for management, including guidance on anti-infective agents and use of growth factors. In addition, awareness and proper actions regarding TLS and neutropenia are key to preventing treatment delays, dose reductions, or treatment discontinuation. Adequate planning for TLS and neutropenia is critical to optimize patient outcomes.

Improving Outcomes for Patients With Chronic Lymphocytic Leukemia.

Mazyar Shadman, MD, MPH, and Amy Goodrich, CRNP, reviewed data regarding the mechanistic activity, efficacy, and safety of approved and emerging therapeutic options for chronic lymphocytic leukemia (CLL) and strategies for managing adverse events associated with approved therapies for CLL.

Lymphoma Therapy and Adverse Events: Nursing Strategies for Thinking Critically and Acting Decisively.

BACKGROUND: Multiple treatment options, combined with disease heterogeneity, have created nursing challenges in the management of adverse events (AEs) during antilymphoma therapy. Testing has revealed that less than half of participating nurses correctly graded peripheral neuropathy and neutropenia related to antilymphoma regimens. OBJECTIVES: This article identifies nursing challenges in the management of AEs associated with therapy for lymphomas and describes how strategies in critical thinking can help meet those challenges. METHODS: A comprehensive literature search in oncology nursing, nursing education, and critical thinking was conducted; participant responses to pre- and post-tests at nursing education programs were evaluated; and a roundtable meeting of authors was convened. FINDINGS: Oncology nurses can cultivate critical thinking skills, practice thinking critically in relation to team members and patients, leverage information from the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events, and manage workflow to allow more opportunity for critical thinking.

Bendamustine: a novel cytotoxic agent for hematologic malignancies.

A significant need exists for effective and well-tolerated treatments for patients with hematologic malignancies. Bendamustine hydrochloride is a novel cytotoxic agent that possesses alkylator and purine-like structural groups, which may confer a unique mechanism of action. Bendamustine recently was approved by the U. S. Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL) and currently is being used in clinical trials for a number of hematologic and solid tumors. Bendamustine has demonstrated promising clinical activity in patients with hematologic malignancies and has manageable toxicities when administered as monotherapy or in combination with other agents. In clinical trials, nausea, fatigue, vomiting, fever, diarrhea, constipation, and headache were the most commonly reported nonhematologic side effects. Reversible myelosuppression also was reported. Nurses need to understand the efficacy and safety profiles of bendamustine to educate patients and their families about its use and expected side effects. Knowledge of specific measures for preventing and managing associated side effects and dose modifications is integral to the provision of optimal care.

Constitutional duplication of a region of chromosome Yp encoding AMELY, PRKY, and TBL1Y: implications for sex chromosome analysis and bone marrow engraftment analysis.

Amelogenin has chromosome X (AMELX) and Y (AMELY) homologs that can be differentiated based on the length of polymerase chain reaction (PCR) amplification products. In addition to being useful for gender identification, analysis of amelogenin has utility for monitoring bone marrow engraftment in patients after a sex-mismatched bone marrow transplant, characterizing sex chromosome abnormalities, and for forensic purposes for analyzing mixtures of male and female DNA. Here, we describe two brothers in which PCR analysis demonstrated twofold greater AMELY products compared with AMELX products. Karyotype and X/Y fluorescence in situ hybridization analysis demonstrated a single copy of the X and Y chromosomes without any identifiable abnormalities. Oligonucleotide comparative genomic hybridization array analysis demonstrated a duplication of a portion of chromosome Yp that encompassed a region of at least 2.6 Mb but not greater than 4.0 Mb. The amplified region contains the genes AMELY, transducin (beta)-like 1 protein Y (TBL1Y), and protein kinase Y (PRKY). To our knowledge, duplication of this region has not previously been reported. The family history is unremarkable, and the brothers are without ap-parent dysmorphic features. Although this and other genetic variants involving AMELY are uncommon, one should use caution when using amelogenin for sex chromosome analysis and bone marrow engraftment analysis.

Emerging therapeutic options for B-cell disorders: idiopathic thrombocytopenic purpura and chronic lymphocytic leukemia.

B-cell disorders include a large group of malignant and nonmalignant diseases with tremendous variation in incidence, natural history, treatment, and prognosis. This article will focus on adult idiopathic thrombocytopenic purpura (ITP) and chronic lymphocytic leukemia (CLL). Clinicians must individualize treatment for ITP and CLL to each patient. Observation without intervention is appropriate for some patients, whereas immediate treatment is indicated for others. Deciding when to treat and which agents to use can be difficult, but new therapeutic options are emerging for both conditions.

A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

In an attempt to exploit bcl-2 overexpression and aberrant p53 function, two frequently encountered aberrations that predict marked treatment resistance and worse prognosis in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), we combined theophylline, pentostatin, and chlorambucil at two dose levels (cohort I: 30 mg/m(2); cohort II: 20 mg/m(2)) on a 21-day cycle for up to six courses. We employed a phase I/II design to determine feasibility, define the maximum tolerated dose (MTD), and explore the impact of biologic modulation on response and time to progression (TTP) in 20 patients with relapsed or refractory CLL and NHL. Eight patients were enrolled in cohort I. They demonstrated a response rate (RR) of 28% and a 16.5-month TTP after receiving a median of two cycles. A 50% RR was observed in this cohort when patients with adverse histologies were excluded. Because of myelotoxicity, this dose level defined the MTD, and de-escalation occurred. All 12 patients in cohort II received 20 mg/m(2) chlorambucil. A 50% RR and an 18-month TTP were observed after a median of 5.5 cycles. An RR of 47% and a complete remission (CR) of 5% were observed for the entire group, although responses and TTP varied greatly by histology. Significant activity was observed in patients with B-cell CLL and follicular lymphoma (FL). RR and TTP for fludarabine-sensitive/naïve and fludarabine-refractory (FR) B-cell CLL patients were 66 vs 25% and 20 vs 8.5 months, respectively. Both FL patients responded (one with partial remission and one with CR), with a 22.5-monthly median TTP. For responding patients, median TTP and overall survival (OS) was 21 and 69 months, respectively, compared to a median TTP of 2 months and an OS of 13.5 months for nonresponders. The combination of pentostatin, chlorambucil, and theophylline is the active regimen in patients with FL and B-cell CLL.