Carboplatin desensitization - simplified 4-step 2-bag method.

INTRODUCTION: Our cancer program adopted a method for carboplatin desensitization (4-step 2-bag method) that administers the same intensity of drug exposure with a simplified approach to product management in comparison to a published protocol (4-step 4-bag method). METHODS: The intensity of carboplatin administration for 1:1,000, 1:100, 1:10, and 1:1 dilutions and concomitant fluid administration were compared for the 4-step 2-bag (bags A, B) and 4-step 4-bag (bags 1, 2, 3, 4) methods. Pharmacy preparation of bags A and B is described. A succinct overview of the desensitization procedure is provided. Important considerations germane to pharmacy practice are presented. Chart review of patients who underwent carboplatin desensitization with the 4-step 2-bag method between 7/13/2021 and 11/22/2023 was performed to demonstrate institutional use. RESULTS: The 4-step 2-bag method delivers similar rates of drug intensity from start of desensitization to completion of the planned dose as the previously published 4-step 4-bag method. Accuracy of regimen-based dose administration is assured by infusion of bag B contents irrespective of infusion interruptions or rate changes necessitated by patient tolerance. Bag A provides the 1:1000 dilution in a pharmaceutically elegant manner using administration rates and volumes compatible with clinical practice. CONCLUSION: The 4-step 2-bag method for carboplatin desensitization administers controlled drug titration corresponding to 1:1000, 1:100, 1:10, and 1:1 dilutions for dose administration using two compounded admixture bags. Inaugural clinical use of the 4-step 2-bag method for carboplatin desensitization at our healthcare facility has proceeded with expected patient tolerance.

A Prospective Survey of Outpatient Medication Adherence in Adult Allogeneic Hematopoietic Stem Cell Transplantation Patients.

Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) population. The objective of this cross-sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo-HSCT. An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow-up after allo-HSCT. Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses. In the entire cohort, 51% of subjects (n = 102) reported nonadherence to nonimmunosuppressant medications (95% confidence interval [CI], 44.07% to 57.93%) on the Morisky Medication Adherence Scale. Of the 153 patients taking oral immunosuppressant medications at the time of the survey, 58 (37.9%) reported nonadherence to immunosuppressant therapy (95% CI, 30.22% to 45.6%), as measured by the Immunosuppressant Therapy Adherence Scale. Younger age and distress were associated with medication nonadherence. Nonadherence to immunosuppressant therapy was associated with mild chronic graft-vs-host disease (cGVHD), and a similar trend was observed for moderate cGVHD. Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo-HSCT recipient, and further study to identify interventions to improve adherence in these patients is warranted.

Low incidence of pneumocystis pneumonia utilizing PCR-based diagnosis in patients with B-cell lymphoma receiving rituximab-containing combination chemotherapy.

Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R-CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R-CHOP administration in patients with B-cell lymphoma. Consecutive patients diagnosed with B-cell lymphoma receiving R-CHOP were evaluated from chemotherapy initiation until 180 days after the last administration. The primary outcome was cumulative incidence of PJP infection. Secondary endpoints included the association of rituximab, prednisone and subsequent chemotherapy with PJP infection risk. A total of 689 patients (53% male, median age 66 years) were included. Seventy-three percent of patients completed at least 6 cycles of R-CHOP treatment. Median rituximab and prednisone cumulative doses were 3950 mg and 5325 mg, respectively. Median daily prednisone dose through end of treatment was 45 mg (range 7.6 mg to 119 mg). The cumulative incidence of PJP was 1.51% (95% CI 0.57-2.43, at maximum follow-up of 330 days), below 3.5%, the conventional threshold for prophylaxis. Univariate analysis did not detect a statistically significant association between PJP and rituximab, steroids, or receipt of additional chemotherapy in this patient population. Our results demonstrate a low occurrence of Pneumocystis pneumonia during R-CHOP treatment of B-cell lymphoma and argue against universal anti-Pneumocystis prophylaxis in this setting. Further investigations should focus on targeted anti-Pneumocystis prophylaxis for patients presenting with high-risk baseline characteristics or when receiving rituximab-inclusive intensive combination chemotherapy regimens as treatment for other aggressive lymphoma subtypes. Am. J. Hematol. 91:1113-1117, 2016. © 2016 Wiley Periodicals, Inc.

Relationship of Sulfamethoxazole Therapeutic Drug Monitoring to Clinical Efficacy and Toxicity: A Retrospective Cohort Study.

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is the treatment of choice for infections caused by Pneumocystis jiroveci, Stenotrophomonas maltophilia, and Nocardia species, but the utility of therapeutic drug monitoring (TDM) is unclear. The objective of this study was to evaluate the association between peak sulfamethoxazole (SMX) serum levels and clinical outcomes to determine the utility of TDM of TMP/SMX. METHODS: This study was conducted in patients receiving treatment with TMP/SMX for culture-positive infection who underwent TDM from 2003 to 2013. Peak SMX levels were classified as below target (<100 mcg/mL), within target (100-150 mcg/mL), or above target (>150 mcg/mL). The effect of initial SMX levels on clinical outcomes was compared using propensity score adjusted multivariable Cox models. RESULTS: A total of 279 patients had SMX monitoring performed. The primary infecting organisms were P. jiroveci (47%) and S. maltophilia (38%). A majority of patients (74%) had an SMX peak level outside of the target range. Using direct regression propensity score adjustment, there was no significant difference between rates of clinical failure and initial peak SMX level (<100 mcg/mL versus 100-150 mcg/mL: hazard ratio 0.92, 95% confidence interval, 0.28-3.07 and >150 mcg/mL versus 100-150 mcg/mL: hazard ratio 1.92, 95% confidence interval, 0.72-5.09). Similarly, there was no relationship between SMX level and toxicity (P = 0.42). CONCLUSIONS: Sulfamethoxazole serum levels outside the target range were not associated with increased rates of clinical failure in patients treated with TMP/SMX. There was also no association found between peak SMX levels and rates of adverse events. Although this study cannot disprove that dose adjustments after the initial SMX peak level may have affected clinical outcomes, the results suggest that the utility of SMX TDM may be limited to a subset of patients and requires further prospective investigation.

Antineoplastic agents and the associated myelosuppressive effects: a review.

Bone marrow is a complex organ responsible for the regulation of hematopoietic cell distribution throughout the human body. Patients receiving antineoplastic agents as a therapeutic intervention for hematologic malignancy often experience varying degrees of myelotoxicity. Antineoplastic agents cause hypocellularity in marrow resulting in a reduction in hematopoietic tissue activity and a corresponding decline in cell production. Quantifying the adverse effects on hematopoiesis is based on the properties of a single agent, the use of individual drugs within a combination chemotherapy regimen, and the course, or courses, of chemotherapy designed to treat cancer. The direct or indirect suppression of erythrocytes, granulocytes, and megakaryocytes has potential for multiple negative clinical consequences ranging from increased monitoring of blood counts to life-threatening infection and death. This review will provide an overview of the structure and function of competent adult bone marrow, describe the process of hematopoiesis, and characterize the myelotoxicities associated with common antineoplastic agents currently used in the treatment of cancer.