Search

Mary Lou Affronti,1 Joseph Bubalo2 1Duke University Medical Center, Durham, NC, 2Oregon Health and Science University Hospital and Clinics, Portland, OR, USA Abstract: Prevention of chemotherapy-induced nausea and vomiting (CINV) is a key component of treatment for patients with cancer. Guidelines are available to assist prescribers in the management of CINV associated with single-day chemotherapy regimens. However, currently there are no clear guidelines for management of CINV in patients receiving multiple-day chemotherapy regimens. Serotonin (5-HT3) receptor antagonists are a mainstay in preventing CINV, and palonosetron, given its longer half-life and duration of action relative to other 5-HT3 receptor antagonists, may be a useful option for managing CINV in multiple-day chemotherapy. Here we provide an overview of CINV and CINV treatment options, with a focus on palonosetron. We describe existing challenges in managing CINV, and discuss two patients receiving multiple-day chemotherapy, in whom CINV was managed successfully with palonosetron. Keywords: chemotherapy-induced nausea and vomiting, palonosetron, multiple-day chemotherapy, 5-HT3 receptor antagonist

Introduction'Real-world' data for mold-active triazoles (MATs) in the treatment of invasive fungal infections (IFIs) are lacking. This study evaluated usage of MATs in a disease registry for the management of IFIs.MethodsData were collected for this multicenter, observational, prospective study from 55 US centers, between March 2017 and April 2020. Eligible patients received isavuconazole, posaconazole, or voriconazole as MAT monotherapy (one MAT) or multiple/sequenced MAT therapy (more than one MAT) for prophylaxis or treatment. Patients were enrolled within 60 days of MAT initiation. The primary objective was to characterize patients receiving a MAT and their patterns of therapy. The full analysis set (FAS) included eligible patients for the relevant enrollment protocol, and the safety analysis set (SAF) included patients who received ≥ 1 MAT dose.ResultsOverall, 2009 patients were enrolled in the SAF. The FAS comprised 1993 patients (510 isavuconazole; 540 posaconazole; 491 voriconazole; 452 multiple/sequenced MAT therapies); 816 and 1177 received treatment and prophylaxis at study index/enrollment, respectively. Around half (57.8%) of patients were male, and median age was 59 years. Among patients with IFIs during the study, the most common pathogens were Aspergillus fumigatus in the isavuconazole (18.2% [10/55]) and voriconazole (25.5% [12/47]) groups and Candida glabrata in the posaconazole group (20.9% [9/43]); the lungs were the most common infection site (58.2% [166/285]). Most patients were maintained on MAT monotherapy (77.3% [1541/1993]), and 79.4% (1520/1915) completed their MAT therapies. A complete/partial clinical response was reported in 59.1% (591/1001) of patients with a clinical response assessment. Breakthrough IFIs were reported in 7.1% (73/1030) of prophylaxis patients. Adverse drug reactions (ADRs) were reported in 14.7% (296/2009) of patients (3.9% [20/514] isavuconazole; 11.3% [62/547] posaconazole; 14.2% [70/494] voriconazole).ConclusionsIn this 'real-world' study, most patients remained on their initial therapy and completed their MAT therapy. Over half of patients receiving MATs for IFIs had a successful response, and most receiving prophylaxis did not develop breakthrough IFIs. ADRs were uncommon.

Background: Despite prophylaxis, acute graft-versus-host disease (aGVHD) occurs in up to 40% to 60% of patients undergoing an allogeneic hematopoietic stem cell transplantation (alloHSCT). Tacrolimus remains a common GVHD prophylactic medication used in combination with mycophenolate or methotrexate., Objective: The purpose of this study was to compare tacrolimus levels up to day +56 to clinical outcomes in patients who underwent alloHSCT., Methods: This was a retrospective cohort study of adult patients who underwent alloHSCT between January 2009 and April 2019 at Oregon Health and Science University (OHSU) Hospital. A logistic regression analysis was performed using SAS software to evaluate the association between tacrolimus concentration range and the GVHD grade outcome., Results: There were 295 patients included in the study. The median patient age was 53 years (range 18-72), the majority were males (55%), with a median comorbidity index of 2 (range 0-9). Most patients received peripheral blood stem cell transplant (95%). The median tacrolimus levels were divided into 4 groups: (1) between 3.8 and 4.9 ng/mL, (2) 5.0 and 7.9 ng/mL, (3) 8.0 and 9.9 ng/mL, and (4) 10.0 and 10.7 ng/mL in 8 (2.7%), 206 (69.8%), 71 (24.1%), and 10 (3.4%) of patients, respectively. The odds ratio of 0.193 (95% confidence interval [CI]: 0.045-0.836) suggested that patients in the tacrolimus 8 to 12 ng/mL range were approximately 80.5% less likely to have grade 3 to 4 aGVHD compared to those in the 5 to 8 ng/mL range., Conclusion and Relevance: Overall, we found that higher levels of tacrolimus (range 8-12 ng/mL) in the first 8 weeks post-transplant were associated with improved outcomes without increased rate of relapse., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Addition of midostaurin to standard "7+3" (cytarabine and anthracycline) significantly prolongs overall and event-free survival. At University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (R/R) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated. There is limited data on the use of FLT3-inhibitors with high-dose cytarabine regimens in AML., Objective: This study aimed to evaluate the safety and efficacy of the combination of midostaurin with CLAG-M versus midostaurin plus 7+3 in FLT3-mutated AML patients., Methods: This is a retrospective, multicenter review including FLT3-mutated AML patients undergoing (re)induction chemotherapy with either CLAG-M or 7+3 at UW/FHCC, Oregon Health & Science University, and Swedish Cancer Institute. The primary outcome was incidence of adverse events. Secondary outcomes included disease response per ELN2017 criteria and 28-day mortality. Excluded were patients on clinical trials or who started midostaurin 30 days after chemotherapy., Results: Eighty patients treated from September 2016 to December 2023 were included; 36 patients received CLAG-M, and 44 patients 7+3. Baseline characteristics were similar across all institutions. Adverse event rates were similar between the 2 cohorts, except diarrhea and bleeding which were more common in the 7+3 cohort. The rate of complete remission (CR) plus CR with incomplete blood count recovery did not significantly differ between the 2 cohorts: CLAG-M, 86% versus 7+3, 70% ( P = 0.11)., Conclusion & Relevance: The toxicity profile of CLAG-M combined with midostaurin is comparable with the combination of 7+3 with midostaurin, and induces high remissions rates in adults with FLT3-mutated AML., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GB: Honorarium for presentation from Postgraduate Healthcare Education, LLC (supported by educational grant from Bristol Myers Squibb). JB: Research funding from Angiocrine Bioscience. AC: Honorarium for presentation from Oncology Pharmacy Network. JC: Currently employed by Servier Pharmaceuticals. AH: Research funding from Jazz Pharmaceuticals, Imago Pharma, Bayer, Gilead/Forty Seven, Incyte, Karyopharm Therapeutics, Disk Medicine. Honoria for lectures/presentation from Curio sciences. Consulting with Agios, Abbive, and Notable labs. SN: Consulting or advisory role with Bristol Myers Squibb/Celgene/Juno, Janssen, Sanofi, Regeneron, ORIC Pharmaceuticals. Honoraria from Medscape. MO: Consulting or advisory role with GlycoMimetics, Cascadia Labs, Merck, Daiichi Sankyo, Biosight. Other relationships with Celgene, GlycoMimetics, Grifols.

Autologous stem cell transplantation is a standard treatment strategy for patients with multiple myeloma that requires effective mobilization and apheresis of peripheral blood progenitor cells; however, in the current era of novel myeloma induction therapies, the optimal mobilization regimen to enhance stem cell yield while limiting toxicity and resource utilization remains unknown. In this multicenter retrospective study, we assessed apheresis and transplant outcomes in myeloma patients mobilized with granulocyte colony stimulating factor (G-CSF) alone (n = 62), G-CSF with chemotherapy (n = 43), or G-CSF with the CXCR4 antagonist plerixafor (n = 417). Compared to patients treated with G-CSF alone, the plerixafor group required significantly fewer median apheresis sessions (1 vs 2, p = 0.0023) with higher CD34+ stem cell yield (9.9 vs 5.8 × 10 6 cells/kg, p < 0.001) and had significantly faster engraftment of neutrophils (HR 1.54, 95% CI 1.17-2.03) and platelets (HR 2.24, 95% CI 1.69-2.96) after transplant. Additionally, the plerixafor group showed a significantly better toxicity profile and lower adverse event rate than patients treated with G-CSF alone (p = 0.0028) or chemomobilization (p < 0.0001), with a trend toward reduced survival in chemomobilization patients. Taken together, these data support the routine use of plerixafor-based mobilization to increase apheresis efficiency and reduce toxicity in myeloma patients undergoing transplant., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Acute encephalopathy, manifesting clinically as delirium, is a common but often unrecognized complication of hematopoietic cell transplantation (HCT). Delirium can occur in patients of any age and is observed after autologous or allogeneic HCT. Although delirium has been studied primarily during initial HCT hospitalizations in recipients of myeloablative conditioning, recent investigations have identified delirium later post-transplantation and in recipients of reduced-intensity conditioning. Acute encephalopathy can be driven by infectious complications, medications, tissue damage, and/or organ dysfunction. Altered consciousness, either mild or profound, is often its only clinical manifestation. Identifying delirium is essential to overall HCT care, because patients who experience delirium have longer hospitalization and recovery times and are at risk for other poor post-HCT outcomes. Given the critical nature of this common complication and the ongoing expansion of HCT for more vulnerable populations, the American Society of Transplantation and Cellular Therapy (ASTCT) recommends intensifying research into post-HCT cognitive changes and establishing standardized definitions that encompass the full spectrum of altered consciousness for clinical care purposes and to provide benchmark endpoints for future research studies. To capture a range of acute neurocognitive changes specifically found in HCT patients (often referred to as acute encephalopathy), the ASTCT proposes a new diagnosis, transplantation-associated altered mentation and encephalopathy (TAME). The TAME diagnosis includes HCT patients who meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for delirium and those with acute neurocognitive changes who do not meet all the DSM-5 criteria for delirium (subsyndromal delirium). Early TAME is defined as occurring during conditioning or ≤100 days post-HCT, whereas late TAME occurs >100 days post-HCT in patients with additional HCT-related complications. This manuscript establishes clear diagnostic criteria and discusses factors that can potentially impact the development of TAME, as well as the workup and management of TAME., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AJP reports consulting fees from AbbVie, BeiGene, Pfizer, Sanofi-Aventis, and Servier. MRB serves as a member on an advisory board or as a consultant for Autolus Therapeutics, BMS/JUNO Therapeutics, Chimeric Therapeutics, CRISPR Therapeutics, IN8bio, Incyte, Iovance Biotherapeutics, KITE/Gilead, Novartis, PhysIQ, and Sana Biotechnology and is on the speakers’ bureau for ADC Therapeutics, Agios, BMS, Kite/Gilead, Incyte, Sanofi, and Servier. JB reports consulting fees from Sanofi-Aventis. MBG reports research support from Actinium Pharmaceuticals, Amgen, and Sanofi and has served on an advisory board for Sanofi and as a consultant for Novartis. AG reports consulting fees from Sanofi-Aventis. SCH has served as a speaker for Jazz Pharma and Sanofi, has received grant funding from Jazz Pharma, and has served as a consultant for Servier. JK reports consulting fees from Sanofi-Aventis. SM reports grant funding from Horizon; service on advisory boards for Calliditas, Chinook, Travere, and US Renal Care; and service on speaker’s bureaus for Bayer and Calliditas. MSC serves on the speaker’s bureau and as a consultant for Sanofi. C-HP reports support by grant CA21765 from the National Cancer Institute and American Lebanese Syrian Associated Charities, and honorarium from Amgen and Novartis., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed the real-world use of mold-active triazoles (MATs) for the prevention of IFDs., Methods: This subgroup analysis of a multicenter, observational, prospective registry in the United States from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient characteristics and patterns of MAT use. Exploratory assessments included the frequency of breakthrough IFDs and MAT-related adverse drug reactions (ADRs)., Results: A total of 1177 patients (256 isavuconazole, 397 posaconazole, 272 voriconazole, and 252 multiple/sequenced MATs at/after index/enrollment) were included in the prophylaxis subgroup analysis. Patient characteristics were similar across MAT groups, but risk factors varied. Hematological malignancy predominated (76.5%) across all groups. Breakthrough IFDs occurred in 7.1% (73/1030) of patients with an investigator's assessment (5.0% [11/221] isavuconazole; 5.3% [20/374] posaconazole; 4.0% [9/226] voriconazole; and 15.8% [33/209] multiple/sequenced MATs). Aspergillus (29.5% [18/61]) and Candida (36.1% [22/61]) species were the most common breakthrough pathogens recovered. ADRs were reported in 14.1% of patients, and discontinuation of MATs due to ADRs was reported in 11.1% of patients (2.0% [5/245] isavuconazole; 8.2% [30/368] posaconazole; and 10.1% [27/267] voriconazole)., Conclusions: Breakthrough IFDs were uncommon in patients who received MATs for prophylaxis. Candida and Aspergillus species were the most commonly reported breakthrough pathogens. The discontinuation of MATs due to ADRs was infrequent. These findings support prophylactic strategies with isavuconazole, posaconazole, and voriconazole in high-risk patients., Competing Interests: Potential conflicts of interest. M.H.N. reports grants from Astellas Pharma Global Development, Inc., Scynexis, Mayne Pharma, Pulmocide, and T2 Biosystems and serves as consultant to T2 Biosystems and MiraVista. L.O.Z. reports grants from Gilead, Pfizer, Scynexis, Cidara, and Pulmocide; payment or honoraria from Pfizer and F2G; and participation on boards for Cidara, F2G, Pfizer, Eurofins, and Appili. P.G.P. reports grants from Scynexis, Mayne Pharma, Astellas, and Cidara and consulting fees from F2G, Matinas, and Cidara. T.J.W. reports grants for experimental and clinical antimicrobial pharmacology, therapeutics, and diagnostics to his institution from Allergan, Amplyx, Astellas, Lediant, Merck, The Medicines Company, Scynexis, Shionogi, T2 Biosystems, Tetraphase, and Viosera and has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Karyopharm, Leadiant, The Medicines Company, Merck, Methylgene, Partner Therapeutics, Pfizer, Scynexis, Shionogi, Statera, and T2 Biosystems. J.B. reports payment or honoraria from medSynergy and participation on an advisory board for Pfizer. B.D.A. reports grants from Leadiant; royalties from UpToDate; participation on advisory boards for HealthTrackRx, Merck, and ThermoFisher; leadership or fiduciary roles on other boards for the IDSA; and acting as principal investigator for clinical trial sites for F2G, Scynexis, Cidara, and Shire/Takeda. M.H.M. reports grants and consulting fees from Astellas; grants from F2G and Scynexis; and consulting fees from Scynexis and PSI. J.J. and Y.S. are/were employees of Astellas Pharma Global Development, Inc. G.R.T. has nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The purpose of this single-center retrospective case series was to evaluate the efficacy and safety of 300-mg once-monthly intravenous (IV) pentamidine prophylaxis in 702 adult allogeneic hematopoietic stem cell transplant (HSCT) patients. We observed no cases of Pneumocystis jirovecii pneumonia (PJP) following IV pentamidine administration. Breakthrough Nocardia and Toxoplasma infections were observed in 7 (1%) and 5 (0.7%) patients, respectively. The most commonly reported adverse event was nausea. Monthly IV pentamidine is a reasonable alternative to trimethoprim-sulfamethoxazole (TMP-SMX).

Netupitant/palonestron (NEPA, Akynzeo™) is a fixed combination of netupitant 300 mg and palonosetron 0.5 mg that is indicated for the prevention of chemotherapy-induced nausea and vomiting (CINV). NEPA is supplied as a hard gelatin capsule and indicated to be administered whole with or without food. The efficacy of NEPA was maintained when administered as an oral dose of netupitant given concomitantly (in separate formulations after removal from the hard gelatin capsule) with a single oral dose of palonosetron. At our institution, two patients experienced difficulty swallowing the capsule leading to opening the capsule and individual administration of the medications. We observed that the efficacy was maintained when the opened NEPA capsule was administered as individual medications. We report the details of these two patient cases.

The thrombopoietin receptor agonists (TPO-RAs) romiplostim, eltrombopag, avatrombopag, and lusutrombopag carry unique US Food and Drug Administration (US FDA)- and European Medicines Agency (EMA)-approved indications and may be used to increase platelet counts in a variety of conditions. Current indications for available TPO-RAs include treatment of chronic immune thrombocytopenia (ITP) in cases of insufficient response to prior treatment (avatrombopag, eltrombopag, romiplostim), management of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure (avatrombopag, lusutrombopag), management of severe aplastic anemia (eltrombopag), and management of thrombocytopenia associated with interferon-based therapy for hepatitis C (eltrombopag). Across current indications, pharmacists can assist in stabilizing platelet counts and help to reduce large undulations commonly seen when starting, stopping, or transitioning between these agents. If therapy modifications may benefit the patient, pharmacists should discuss possible changes with the patient's treatment team or treating physician. When used for ITP, romiplostim, eltrombopag, and avatrombopag stimulate TPO receptors on hematopoietic stem cells (also known as c-Mpl, or CD110) to promote platelet production; however, romiplostim is the only TPO-RA that binds at the same site as endogenous TPO. These subtle mechanistic differences may explain why switching TPO-RA may be clinically advantageous in some situations. As pharmacists are called to counsel patients on TPO-RA use, a deep understanding of potential adverse events and management strategies, as well as appropriate monitoring, will increase the likelihood that patients meet their goals of therapy in the shortest timeframe. Other uses of TPO-RAs are also discussed in this review, including use following hematopoietic stem cell transplant, use in myelodysplastic syndrome, and use in chemotherapy-induced thrombocytopenia., (© 2021. The Author(s).)

Background: The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilars Task Force was charged to develop educational activities and resources to assist members when implementing biosimilar medicines into their local practice. To facilitate the process, the task force conducted a survey in order to understand biosimilar implementation practice by ISOPP members across the world and the challenges that oncology pharmacists face when adopting biosimilars into their clinical practice., Methods: A cross-sectional survey was conducted between 20 April 2019 and 27 May 2019. Members of ISOPP and a number of national oncology pharmacy groups were invited to complete the survey. The survey contained 29 items and consisted of three sections: respondents’ demographics, respondents’ institutional practice relating to biosimilar implementation and post implementation practice at the respondents’ institutions. Descriptive statistics were utilized to analyze the survey results., Results: A total of 265 ISOPP members were surveyed, with 50 members providing a response (response rate = 19%). In addition, 40 nonmembers participated in the survey, bringing the total to 90 respondents. The most common factors that influence the decision to implement use of a biosimilar as reported by respondents are medication costs/pricing (92%), available clinical data (73%), and product availability (63%). Respondents also commented on the barriers to biosimilar implementation at their institutions, which included a reluctance of prescribers to use biosimilars (due to the lack of familiarity or perceived inferiority), a reluctance to switch established patients from an originator to a biosimilar and the preferences of insurance companies or funding bodies., Conclusion: The results of this survey reinforce the need for greater education and training for health care professionals in the use of biosimilars, the importance of sharing good practice, and a need for standardization.

Background: The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilar Task Force was charged to develop educational resources to address the learning needs related to biosimilars use of oncology pharmacy practitioners. To facilitate the process, the task force conducted a survey in order to identify unmet education needs as well as barriers for obtaining biosimilar education among oncology pharmacy practitioners., Methods: A cross sectional survey was conducted between 10 December 2018 and 18 February 2019. Members of International Society of Oncology Pharmacy Practitioners and national oncology pharmacy groups were invited to complete the survey. The survey contained 22 items and consisted of four sections. Descriptive statistics were utilized to analyze the survey results., Results: A total of 363 International Society of Oncology Pharmacy Practitioners members were surveyed, with 75 members providing a response (response rate = 21%). In addition, 11 non-International Society of Oncology Pharmacy Practitioners members also participated in the survey, bringing the total to 86 respondents. The top three areas in which respondents reported learning needs included evaluating comparative efficacy of a biosimilar to an originator’s product (74.4%), managing the switchover to a biosimilar from the original product (74.4%), and understanding medication safety issues in relation to biosimilars use (73.3%). The most common challenges faced in obtaining education on biosimilars included limited financial support for education on biosimilar products (38.4%), heavy workload (31.4%), and inadequate educational resources (27.9%)., Conclusion: This survey has identified numerous biosimilar learning needs as well as challenges faced in obtaining biosimilars education among oncology pharmacy practitioners. Educational activities should be created to address these learning needs, and innovative strategies should be considered to overcome practitioner’s barriers in obtaining biosimilars education.

With the development of innovative cancer treatments over recent decades, the cost of cancer care has risen exponentially, limiting patient access to patented originator biotherapeutics in many countries. The introduction of biosimilars to the market has created new opportunities as well the need for changes in practice within healthcare institutions. A ‘biosimilar’ is a biotherapeutic product which is highly similar in terms of quality, safety and efficacy to an already licensed originator product. Although biosimilars lack clinically meaningful differences in therapeutic activity as compared to the originator product, these complex biological molecules are not considered identical chemical copies, unlike generics, and minor differences in molecular structure and inactive compounds may exist. A thorough understanding of these differences and their clinical implications is necessary for optimising medicines-use practices involving biosimilars. This position statement, developed by the International Society of Oncology Pharmacy Practitioners Biosimilars Taskforce, aims to provide the global oncology pharmacy community with guidance to support decisions around biosimilar use. The 11 statements cover the regulation and evaluation of biosimilars, practical issues around local implementation, the education of healthcare staff and patients, and the requirement for ongoing pharmacovigilance and outcome monitoring.

High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative antiepileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Lower exposure to active CY metabolites with the use of alternative AEMs could decrease the risk of toxicity but might increase the risk of recurrent malignancy after HCT. Previous studies have not determined whether outcomes with alternative AEMs differ from those with phenytoin in patients treated with BU/CY before allogeneic HCT. We studied a cohort of 2155 patients, including 1460 treated with phenytoin and 695 treated with alternative AEMs, who received BU/CY before allogeneic HCT between 2004 and 2014. We found no differences suggesting decreased overall survival or relapse-free survival or increased risks of relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or regimen-related toxicity associated with the use of alternative AEMs compared with phenytoin. The risk of dialysis was lower in the alternative AEM group than in the phenytoin group. Alternative AEMs are safe for prevention of seizures after BU administration and can avoid the undesirable toxicities and drug interactions caused by phenytoin., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m 2 . Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Doxorubicin, cisplatin, and high-dose methotrexate (HDMTX) are the backbone of pediatric osteosarcoma treatment. However, due to toxicity concerns and the lack of data regarding efficacy in adults, high-dose methotrexate is rarely used in the adult population., Methods: This single-center retrospective study examined 33 patients who received HDMTX (12 g/m 2 , maximum 20 g) for the treatment of osteosarcoma at Oregon Health and Science University (OHSU) from 2011 to 2017. Time to serum methotrexate level ≤0.1 µmol/L was the primary outcome. Secondary outcomes included number of HDMTX doses received, methotrexate-related toxicities, and disease outcomes including histologic response at resection and metastasis-free survival., Results: Median age was 20 years [range 7-38]; 14 patients ≤18 years old and 19 patients >18 years old. Median time to clearance for patients ≤18 years was 79 hours (range 63-116) compared to 120 hours (range 77-315) for patients >18 years (P < 0.001). No correlation between age and histologic response at resection was observed (P = 0.50), but there was a significant positive correlation between the number of HDMTX doses received before resection and histologic response (r = 0.49, P = 0.006). There was no significant difference in metastasis-free survival between age groups, although a trend toward improved survival was noted for patients who received at least seven doses of HDMTX., Conclusion: Age over 18 years correlates with delayed methotrexate clearance and fewer administered doses of methotrexate, without increased toxicity. The potential benefit of HDMTX in young adults with osteosarcoma may outweigh toxicity risks., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The aim of this study was to evaluate the safety and efficacy of aprepitant when used prophylactically to prevent nausea and vomiting during cyclophosphamide-based conditioning regimens. The primary objective of this study was to determine if there was a difference in the number of emesis-free days in patients who received aprepitant as compared to those who received placebo. This prospective, randomized, double blind, placebo-controlled study was performed in 40 adult patients who received a cyclophosphamide-containing HSCT conditioning regimen. Twenty patients were randomized to receive aprepitant, ondansetron, and dexamethasone, and 20 were randomized to receive placebo, ondansetron, and dexamethasone. Complete response (CR) was defined as the absence of emesis and the absence of mild to moderate nausea. The average number of emesis-free days was 14.25 (standard deviation 1.48 days) in the aprepitant group compared to 12.45 days (standard deviation 2.16 days) for patients in the placebo group. Eight patients (40%) in the aprepitant group achieved CR as compared to four patients (20%) in the placebo group. In the setting of cyclophosphamide-containing conditioning regimens, the addition of aprepitant to a standard antiemetic regimen decreased the incidence of emesis as compared to placebo. Aprepitant was well tolerated.

Purpose of Review: To highlight the breadth and types of mental distress experienced by hematopoietic stem cell transplant (HSCT) patients and highlight the need for better prevention and management of delirium., Recent Findings: Recent publications highlight additional risks factors which predict for mental distress during the HSCT process. Despite new medications and additional psychological reports, there is little progress in non-pharmacologic or medication therapy in the prevention and treatment of delirium. Mental distress, especially delirium, is common during the HSCT process. The morbidity associated with delirium and other mental distress can still be significant at 6-12 months after the completion of the procedure affecting patient functioning and quality of life (QOL). Medication interventions may be helpful but should be used sparingly for targeted patients during HSCT. Additional interventions are needed to prevent and treat delirium in HSCT patients.

The Practice Guidelines Committee of the American Society of Blood or Marrow Transplantation (ASBMT) sought to develop an evidence-based review about personalizing busulfan-based conditioning. The Committee sought to grade the relevant published studies (June 1, 2008 through March 31, 2016) according to criteria set forth by the Steering Committee for Evidence Based Reviews from ASBMT. Unfortunately, the published literature was too heterogeneous and lacked adequately powered and sufficiently controlled studies for this to be feasible. Despite this observation, the continued interest in this topic led the Practice Guidelines Committee to develop a list of most frequently asked questions (FAQs) regarding personalized busulfan dosing. This "Considerations" document is a list of these FAQs and their responses, addressing topics of practical relevance to hematopoietic cell transplantation clinicians., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose: Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors., Summary: This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care., Conclusion: The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the antineoplastic population, benefit from many other technologies may have to be inferred based on data from other patient populations. As health systems begin to widely adopt and implement new technologies it is important to critically assess their effectiveness in improving patient safety., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aims: Prophylaxis against Pneumocystis jiroveci pneumonia (PJP) is currently recommended for patients receiving chemoradiation with temozolomide for newly diagnosed glioblastoma multiforme. At our institution, PJP prophylaxis during temozolomide treatment has not been routinely given because of the paucity of supporting data. We investigated the rate of PJP infections in our patients., Patients & Methods: We conducted a retrospective chart review of 240 brain tumor patients treated between 1999 and 2012 with temozolomide and no PJP prophylaxis, 127 of which received concurrent chemoradiation., Results: One in 240 patients (0.4%; 95% CI: 0.01-2.00; median total dose: 7375 mg/m(2); interquartile range: 1300) were diagnosed with PJP., Conclusion: There was a <1% rate of PJP for brain tumor patients treated with temozolomide until progression without PJP prophylaxis.

Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the nontransplantation patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence are unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Survival after hematopoietic stem cell transplantation (HSCT) has improved and the number of allogeneic HSCTs performed annually in the United States is expected to reach 10,000 by 2015. The National Marrow Donor Program created the System Capacity Initiative to formulate mechanisms to care for the growing number of HSCT recipients. One proposed method to increase capacity is utilization of pharmacists to manage drug therapy via collaborative practice agreements (CPAs). Pharmacists have managed drug therapy in oncology patients with CPAs for decades; however, there are limited HSCT centers that employ this practice. Engaging in collaborative practice and billing agreements with credentialed pharmacists to manage therapeutic drug monitoring, chronic medical conditions, and supportive care in HSCT recipients may be cost-effective and enable physicians to spend more time on new or more complex patients. The goal of this paper is to provide a framework for implementation of a CPA and address how it may improve HSCT program capacity., (Copyright © 2013 American Society for Blood and Marrow Transplantation. All rights reserved.)

Objective: To provide pharmacists with a current, comprehensive review of medication adherence challenges and solutions., Data Sources: A computerized search of the PubMed and Medline databases (through July 2008) identified English language review articles on medication adherence using the MeSH terms patient compliance or adherence and medication, drug regimen, or treatment., Study Selection: By the authors., Data Extraction: The results were filtered to include those published in pharmacy journals, and 117 publications were selected based on the content of their abstracts. The final version of this review article used 55 of the 117 publications. An additional 15 publications that provided examples of specific adherence issues were included. A vignette from the authors' experience was used as a case study., Data Synthesis: This article introduces the challenge of patient medication adherence, discusses the various methods by which to monitor medication adherence, describes various treatment- and condition-related barriers to adherence, and discusses the effectiveness of numerous adherence intervention strategies., Conclusion: Nonadherence to a medication regimen may have multiple underlying causes, some of which may be easier to address than others. Open discussion between the pharmacist and patient regarding barriers to adequate medication adherence, followed by a multifaceted, personalized intervention to address these barriers, plays a key role in encouraging patients to adhere to the recommendations of the health care team.

To date there has been no general consensus regarding the effectiveness of N-acetylcysteine as a protective therapy against contrast medium-induced nephropathy. Several phase III clinical trials have been conducted without a proper understanding of N-acetylcysteine pharmacology, particularly with regard to first-pass hepatic metabolism. A review was conducted of the literature concerning contrast medium-induced nephropathy and new studies of human N-acetylcysteine pharmacology were performed. After an analysis was performed, it was concluded that further phase I and phase II trials are needed. The efficacy of N-acetylcysteine in the prevention of contrast medium-induced nephropathy may be demonstrated with the use of higher doses than used in earlier studies, in combination with parenteral administration.

Goals of Work: The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors., Materials and Methods: Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation., Main Results: This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%)., Conclusions: Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.

To date, all available therapies for prostate cancer are plagued by adverse effects. Chemotherapy is no exception. The mechanisms of activity of chemotherapy agents are not cancer-specific. Normal tissues, particularly those that require rapid cell proliferation, are vulnerable to the effects of growth inhibition by these cytotoxic agents. Furthermore, both predictable as well as idiosyncratic toxicities unrelated to the antineoplastic activity of these agents can occur. In some cases, the cause of adverse events may be linked to the vehicle required to suspend water-insoluble chemotherapy drugs. Patient-specific factors can also significantly contribute to the risk of chemotherapy side-effects. However, with optimal clinical care the toxicity of antineoplastic agents can be substantially reduced. Long before chemotherapy is contemplated, it is imperative to limit treatments that reduce patients' capacity to tolerate subsequent chemotherapy. Moreover, offering treatment before patients' performance status declines can significantly improve tolerance of treatment. Once chemotherapy is initiated, the incidence and severity of adverse effects can be reduced through individualized selection of chemotherapy regimens and appropriate use of adjunct medications. Finally, aggressive management of toxicities after they occur lessens their duration and severity. The common toxicities of current chemotherapy regimens for prostate cancer, as well as strategies to limit and manage these toxicities are reviewed.

Carboplatin is effective in the treatment of malignant brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin ototoxicity. Patients underwent monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin-induced hearing loss. STS delayed to 4 h after carboplatin significantly decreased time to development of ototoxicity and rate of ototoxicity when compared with HCG.

A prospective open-label trial was performed to compare the efficacy of dolasetron with that of ondansetron or granisetron (standard therapy) for prevention of nausea and vomiting associated with high-dose chemotherapy with or without total body irradiation followed by hematopoietic stem cell transplantation (HSCT). In a university teaching hospital setting, 62 patients were randomized to receive either dolasetron 100 mg daily or standard doses of ondansetron or granisetron. In addition to objective data such as number of episodes of emesis and quantity of rescue antiemetics required, 100 mm visual analogue scales were used to rate nausea, appetite, and changes in taste. A post-hoc subgroup analysis was performed between groups of patients that were matched for conditioning regimens. Sixty-five percent of the dolasetron-treated patients and 87% of patients in the standard therapy group achieved a major or complete response (P < .05) based on emetic episodes and nausea score. Patients in the standard therapy group used fewer rescue antiemetics and also rated more favorably on selected questions of the visual analogue scale. No differences in safety parameters or adverse effects were reported. At doses prescribed in this study, dolasetron was less effective than granisetron or ondansetron in preventing nausea and vomiting associated with high-dose chemotherapy/total body irradiation followed by HSCT.

Background: The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers., Methods: Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures)., Results: Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment., Conclusions: Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers., (Copyright 2000 American Cancer Society.)

Sodium thiosulfate (STS) provides protection against carboplatin-induced ototoxicity in an animal model. The purpose of this study was to determine the STS dose required for otoprotection, in patients with malignant brain tumors treated with carboplatin in conjunction with osmotic blood-brain barrier disruption. Twenty-nine patients received STS intravenously 2 hr after carboplatin. Doses were escalated from 4 g/m2 to 8, 12, 16 and 20 g/m2 on consecutive months. Audiologic assessment was performed at baseline and monthly. The audiograms were compared with those of 19 similarly treated historical control patients who did not receive STS. The incidence of ototoxicity in the historical control group of patients was 79% (15/19). This group had an average loss of 20.8 +/- 5.9 dB (n = 19) at 8 kHz after one treatment with carboplatin, whereas the STS treatment group lost only 3.7 +/- 2 dB (n = 15) after one treatment. This difference was statistically significant as assessed by Student's t test (P < .05). Furthermore, patients in the STS treatment group with excellent base-line hearing showed little change in hearing thresholds at 8 kHz after the second treatment (8.0 +/- 8.3 dB) (n = 5) compared with the historical control patients with excellent base-line hearing, (40.5 +/- 8.6 dB) (n = 11). Our data support that doses of 16 or 20 g/m2 of STS decrease carboplatin-induced hearing loss without central nervous system entry. Clinical demonstration of an otoprotective effect with a two-compartment system to prevent drug-induced hearing loss, while preserving central nervous system cytotoxicity, has not been reported previously.