Jill S. Bates

Clinical Utility of Rituximab in Chronic Graft-Versus-Host Disease

Objective: To evaluate the use of rituximab in the clinical management of steroid-refractory chronic graft-versus-host disease (GVHD). Data Sources: Literature was accessed through MEDLINE and International Pharmaceutical Abstracts (1990–September 2008), both indexed and nonindexed citations, using the terms rituximab, graft-versus-host disease, monoclonal antibodies, and CD20. In addition, reference citations from the publications identified were reviewed. Study Selection and Data Extraction: All articles discussing rituximab as a therapeutic option in the treatment of GVHD that were published in English and enrolled human study participants were evaluated. Data Synthesis: Rituximab is a genetically engineered chimeric murine monoclonal antibody that binds to the CD20 differentiation antigen found on B-lymphocytes. GVHD is the leading cause of procedural-related morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Chronic GVHD (cGVHD) occurs in up to 70% of individuals undergoing HSCT, and approximately 40% of those patients are refractory to conventional T-lymphocyte–directed therapies. Limited treatments are available for individuals with steroid-refractory cGVHD. Rituximab therapy in individuals with extensive cGVHD has demonstrated clinical efficacy with manageable toxicities in retrospective and prospective studies. Conclusions: Available data suggest that rituximab is a treatment option for patients with extensive steroid-refractory cGVHD. Rituximab may be particularly effective for individuals with steroid-refractory cGVHD manifesting as thrombocytopenia or with sclerodermatous, cutaneous, and rheumatologic involvement.

Denosumab for the Management of Hypercalcemia of Malignancy in Patients With Multiple Myeloma and Renal Dysfunction

Hypercalcemia and renal dysfunction are common sequelae associated with multiple myeloma and portend poor outcomes. Resistance to bisphosphonates and uncertainty regarding dosing in the setting of renal dysfunction could limit the utility of these agents. Weight-based denosumab dosing might be a reasonable alternative for patients with multiple myeloma in the setting of recalcitrant hypercalcemia and renal dysfunction; such a strategy might minimize the risk of profound and prolonged hypocalcemia. The serum calcium levels should be routinely monitored in all patients receiving denosumab for hypercalcemia of malignancy.

Management of menorrhagia associated with chemotherapy-induced thrombocytopenia in women with hematologic malignancy.

Abnormal uterine bleeding in women with a blood dyscrasia, such as leukemia, or who experience thrombocytopenia secondary to myelosuppressive chemotherapy is a clinical condition associated with significant morbidity. Consequently, effective management is necessary to prevent adverse outcomes. Prevention of menorrhagia, defined as heavy regular menstrual cycles with more than 80 ml of blood loss/cycle or a cycle duration longer than 7 days, in this patient population is the goal of therapy. Gonadotropin‐releasing hormone analogs (e.g., leuprolide) are promising therapies that have been shown to decrease vaginal bleeding during periods of thrombocytopenia and to have minimal adverse effects other than those associated with gonadal inhibition. In patients who experience menorrhagia despite preventive therapies, or in patients who have thrombocytopenia and menorrhagia at diagnosis, treatment is indicated. For these women, treatment options may include platelet transfusions, antifibrinolytic therapy (e.g., tranexamic acid), continuous high‐dose oral contraceptives, cyclic progestins, or other therapies for more refractory patients such as danazol, desmopressin, and recombinant factor VIIa. Hormonal therapies are often the mainstay of therapy in women with menorrhagia secondary to thrombocytopenia, but data for these agents are sparse. The most robust data for the treatment of menorrhagia are for tranexamic acid. Most women receiving tranexamic acid in randomized trials experienced meaningful reductions in menstrual bleeding, and this translated into improved quality of life; however, these trials were not performed in patients with cancer. Further clinical trials are warranted to evaluate both preventive and therapeutic agents for menorrhagia in premenopausal women with cancer who are receiving myelosuppressive chemotherapy.

The role of screening and monitoring for bleomycin pulmonary toxicity.

Bleomycin-induced pulmonary toxicity can have a significant impact on patient outcomes. However, no guidelines for ideal screening and monitoring are available. This paper reviews the literature to identify the best way to monitor and reduce patient risk for bleomycin pulmonary toxicity. We have created evidence-based guidelines to help healthcare professionals identify patient risk factors and provide appropriate assessment and monitoring for patients receiving bleomycin therapy.

A Study of layered learning in oncology

Objective. To explore use of pharmacy learners as a means to expand pharmacy services in a layered learning practice model (LLPM), to examine whether an LLPM environment precludes achievement of knowledge-based learning objectives, and to explore learner perception of the experience. Design. An acute care oncology pharmacy practice experience was redesigned to support the LLPM. Specifically, the redesign focused on micro discussion, standardized feedback (eg, rubrics), and cooperative learning to enhance educational gain through performing clinical activities. Assessment. Posttest scores evaluating knowledge-based learning objectives increased in mean percentage compared to pretest values. Learners viewed the newly designed practice experience positively with respect to perceived knowledge attainment, improved clinical time management skills, contributions to patient care, and development of clinical and self-management skills. A fifth theme among students, comfort with learning, was also noted. Conclusion. Layered learning in an oncology practice experience was well-received by pharmacy learners. Data suggest a practice experience in the LLPM environment does not preclude achieving knowledge-based learning objectives and supports further studies of the LLPM.

Impact of a new assay for measuring serum creatinine levels on carboplatin dosing

PURPOSE The impact of converting to the isotope dilution mass spectrometry (IDMS)-traceable serum creatinine (SCr) assay for determining the calculated and delivered dose of carboplatin was studied. METHODS A single-center, retrospective, observational chart review of adult patients who received a dose of carboplatin within one month before and after implementation of the IDMS-traceable SCr assay was conducted using information available in medical records and chemotherapy orders. Patient-specific data were collected and used to calculate a carboplatin dose before and after the SCr assay change using the Cockcroft-Gault equation, with the Calvert et al. formula used to calculate the carboplatin dose based on the target area under the concentration-time curve in the chemotherapy order forms. The primary outcome was the difference in calculated carboplatin dose, assessed as the percent difference between the mean carboplatin dose before and after the assay change. Results Fifty-six patients were included in the data analysis. The mean calculated carboplatin dose was 9.6% greater when the IDMS-traceable assay was used compared with the previous institutional standard enzymatic assay. This difference was statistically significant (p < 0.005). Nearly 50% of patients received a dose of carboplatin that was increased by >10% compared with the dose received before conversion to the IDMS-traceable assay for SCr measurement. CONCLUSION After implementation of the IDMS-traceable assay, the mean calculated carboplatin dose was 9.6% larger than before implementation, and nearly 50% of patients received a dose of carboplatin that was increased by greater than 10% compared with the dose received before the assay change.

Substitution of sodium acetate for sodium bicarbonate for urine alkalinization in high-dose methotrexate therapy

Drug shortages are associated with suboptimal therapy, delayed recovery, increased adverse effects, and higher healthcare costs.[1][1] The FDA Safety and Innovation Act requires manufacturers to provide early notification of any product discontinuation or supply issues.[2][2] This action helped to

A Comparison of Clofarabine-based (GCLAC) and Cladribine-based (CLAG) Salvage Chemotherapy for Relapsed/Refractory AML

Background Salvage regimens for patients with relapsed/refractory acute myeloid leukemia (rrAML) lack comparative data for superiority. Thus, we conducted a retrospective analysis of clofarabine‐based (GCLAC; granulocyte colony‐stimulating factor [filgrastim], clofarabine, high‐dose cytarabine) versus cladribine‐based (CLAG; cladribine, cytarabine, granulocyte colony‐stimulating factor [filgrastim]) regimens in rrAML. Patients and Methods We identified 41 consecutive patients with rrAML who had received either GCLAC or CLAG from 2011 to 2014. The primary outcome measure was the complete remission (CR) rate defined according to the International Working Group criteria. The secondary outcomes included the proportion of patients who underwent allogenic stem cell transplantation and the rate of relapse‐free survival and overall survival. Results We found no significant differences in the baseline characteristics of the patients treated with GCLAC (n = 22) or CLAG (n = 19). The outcomes with these 2 regimens were not significantly different. Patients treated with GCLAC had a CR/CR with incomplete blood count recovery rate of 64% compared with 47% for the patients treated with CLAG (P = .36). Of the GCLAC patients, 45% underwent allogeneic stem cell transplantation compared with 26% of the CLAG patients (P = .32). The median relapse‐free survival after GCLAC and CLAG was 1.59 years and 1.03 years, respectively (P = .75). The median overall survival after GCLAG and CLAG was 1.03 years and 0.70 years, respectively (P = .08). The drug costs were significantly different for GCLAC versus CLAG. Using an average wholesale price, the cost per patient per cycle was

Start using a checklist, PRONTO: Recommendation for a standard review process for chemotherapy orders:

60,821.60 for GCLAC and

Continuous Care Provided Through Comprehensive Medication Management in an Acute Care Practice Model

4910.60 for CLAG. Conclusion A single‐institutional retrospective analysis found no significant differences in the outcomes between GCLAC and CLAG for rrAML patients, although formal comparisons should be performed in a randomized clinical trial. The cost of GCLAC was greater than that of CLAG, which should be considered when evaluating the choice for the salvage chemotherapy options. Micro‐Abstract The data for savage regimens in relapsed/refractory AML is largely based on phase 2, single arm studies and comparative data is scarce. The purpose of this retrospective study was to compare two salvage AML chemotherapy regimens, GCLAC (clofarabine‐based) and CLAG (cladribine based) in 41 patients (22 and 19 in each arm, respectively). There were no statistically significant differences in complete response rates (GCLAC = 64%; CLAG = 47%, P = .36) as well as other endpoints including safety endpoints. GCLAC was associated with significantly higher costs compared with CLAG (