Risk Of Infusion-related Reactions Research Articles

The utility of H2 receptor antagonists in preventing infusion-related reactions to paclitaxel chemotherapy.

Paclitaxel has a risk of infusion-related reactions (IRRs) and despite no prospective evidence, is often given with premedication including a corticosteroid, H1 antagonist, and H2 antagonist (H2RA). Backorders impacted the supply of intravenous H2RAs at our center, and it was removed as routine premedication. The authors compared the incidence of IRR in patients treated without H2RA to patients receiving standard H2RA premedication. The authors reviewed outpatients starting paclitaxel at the Ottawa Hospital from December 2019 to October 2021. Two cohorts were created: patients treated without H2RA premedication (intervention), and those receiving standard H2RA (control). Demographics, treatment, and IRR information were collected retrospectively. Primary end point was rate of grade ≥2 IRRs during first two doses of paclitaxel. A total of 182 patients were treated without H2RA premedication, compared to 184 control patients treated during non-backorder periods. Baseline characteristics included: median age, 63 years; 86% female; and primary tumor 52% breast/24% gynecologic/10% gastric/esophageal/8% lung/6% other. There were no significant differences between cohorts in baseline characteristics. There was no difference in the rate of grade ≥2 IRR between cohorts; 12.1% (22 of 182; 95% confidence interval [CI], 7.7%-17.7%) for patients treated without H2RA, and 15.1% (28 of 185; 95% CI, 10.3%-21.1%) for control patients. The rate of grade ≥3 IRRs were also similar, 4.4% in intervention cohort versus 3.8% in control cohort. The removal of H2RAs from premedication for paclitaxel did not result in an increased incidence of IRRs. The use of H2RAs in preventing IRRs to paclitaxel should be re-evaluated.

Ninety-Minute Daratumumab Infusion Is Safe in Multiple Myeloma

▪Background: Daratumumab, an anti-CD38 monoclonal antibody, was first approved for the treatment of relapsed and refractory multiple myeloma (MM) in December of 2015. The approved initial infusion lasts at least 6.5 hours, second infusion for 4.5 hours and all subsequent infusions over 3.5 hours. The risk of infusion related reactions (IRRs) is very low after the second infusion, and the prolonged continued infusion time results in long days for patients. Because of our success infusing other monoclonal antibodies over shorter times, such as rituximab (Dotson et al Support Care Cancer, 2016), we hypothesized that shortening the daratumumab infusion from 3.5 hours to 90 minutes beginning with the third infusion would not increase the incidence of IRRs.Methods: This is a single-center safety study of an accelerated daratumumab infusion in patients receiving standard of care daratumumab therapy. Patients were eligible once they received at least 2 prior doses of daratumumab, administered per standard prescribing information. Previous IRR was not an exclusion criterion. The accelerated infusion was calculated to deliver 20% of the dose over the first 30 minutes, then the remaining 80% over 60 minutes, resulting in an estimated 90 minute infusion (Table 1). Patients who tolerated the infusion well were allowed to continue the accelerated rate. Premedication regimens were allowed to be altered based on previous tolerability. Simon's two-stage optimal design was utilized to design the study based on the incidence of grade 3 or above IRR. With 80% power the design allows 7 patients to be treated in the first stage, and if no patients experienced ≥ grade 3 IRR, an additional 21 patients would be treated. Out of all 28 patients, if 2 or more experienced ≥ grade 3 IRR, the regimen would be declared as too toxic. The protocol was approved by the cancer institutional review board.Results: Baseline characteristics are listed in Table 2. Twenty eight patients were treated with daratumumab utilizing the accelerated rate, 8 of which received the accelerated infusion with their third dose of daratumumab. The premedication regimen varied patient-to-patient and did not impact tolerability of the accelerated infusion. There were 5 patients who did not receive any steroid premedication and 3 who received reduced doses (< 12 mg) of dexamethasone. Of the 28 patients treated, there was only 1 adverse reaction - a grade 2 hypertension during which the infusion was paused for a patient that had received 10 prior infusions at standard rates. The patient received a diuretic, the infusion was resumed and subsequently increased to the accelerated rate without further incidence of hypertension. There were no grade 3 or higher IRRs. At the 4-week follow-up, all patients remaining on daratumumab treatment continued at the accelerated infusion rate.Conclusion: An accelerated infusion rate of daratumumab delivering 20% of the dose over 30 minutes and 80% over 60 minutes is feasible and well-tolerated in patients who have received 2 prior doses of daratumumab at standard infusion rates. Starting with the third dose of daratumumab therapy, the 90-minute infusion is now standard practice at our institution. [Display omitted] DisclosuresHofmeister:Janssen: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Karyopharm: Research Funding; Celgene: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Thrassos: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab or panitumumab in patients with refractory solid tumors.

2522 Background: The phase I GATTO study explored the feasibility, tolerability and preliminary activity of combining Gatipotuzumab (GAT), a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin-1 (TA-MUC1), and an anti-EGFR antibody. Preclinical evidence suggests a complex interaction between TA-MUC1 and EGFR on the cell surface of epithelial tumors and synergistic antibody dependent cell cytotoxicity activity with the double targeting. Methods: Initially 20 patients with refractory metastatic disease were treated with GAT administered at 1400 mg Q2W in combination with the glyco-optimized anti-EGFR antibody Tomuzotuximab (TOM) at 1200 mg Q2W. Due to the risk of infusion related reactions, three cycles of TOM were given before start of combined treatment with GAT. After this regimen was proven safe and no DLT was observed, 30 additional patients including colorectal cancer (CRC) already treated with anti-EGFR antibodies, non-small cell lung cancer (NSCLC), head and neck and breast cancers received TOM and GAT administered at the same doses, with GAT treatment starting already one week after the first dose of the anti-EGFR antibody. As allowed in the study expansion, Panitumumab (PAN) was used in place of TOM in 9 CRC patients at investigator’s choice. Results: By the time of the final analysis in January 2021, 52 patients were enrolled, and 50 received at least one dose of both GAT and anti-EGFR antibodies. Safety was overall good and results are reported in a separate abstract. Because of the difference in treatment schedule, activity results of the two parts of the study are summarized separately. There were 2 and 4 RECIST partial responses in the first and second part of the study, all in CRC patients. In the expansion phase, the median Progression Free Survival (PFS) of CRC patients who received TOM (10) and PAN (9) was 1.9 and 5.5 months, respectively. There were 2 responses in each subgroup and the duration of response was 3.8 and 7.2 months in patients receiving TOM and PAN, respectively. The PFS for NSCLC was 5.3 months and 2 heavily pretreated patients achieved a prolonged control of disease of 10.6 and 9.4 months. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 in serum. In the extension phase patients with baseline values above median appeared to have improved PFS and overall survival; this was not the case for patients of the first part of the study who received GAT only after 3 doses of TOM. Conclusions: Combination of TA-MUC1 and EGFR targeting antibody is safe and feasible. Interesting anti-tumor activity was observed in heavily pretreated CRC and NSCLC patients. Levels of soluble TA-MUC1 may have predictive value and potentially be a companion biomarker for further development of the combination Clinical trial information: NCT03360734.

Safety and tolerability results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab or panitumumab in patients with refractory solid tumors.

2524 Background: The phase I GATTO study explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab (GAT), a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin-1 (TA-MUC1) and an anti-EGFR antibody. Preclinical evidence suggests a complex interaction between TA-MUC1 and EGFR on the cell surface of epithelial tumors driving carcinogenesis processes and synergistic antibody dependent cell cytotoxicity activity with the dual targeting. Methods: Initially the study enrolled in a primary phase (PP) 20 patients with EGFR positive metastatic solid tumors, for whom no standard treatment was available. The first 6 patients were enrolled into a safety run-in phase and the number of dose-limiting toxicities (DLTs) was evaluated, in order to de-escalate the doses if needed. Patients received GAT administered at 1400 mg Q2W in combination with the glyco-optimized anti-EGFR antibody tomuzotuximab (TOM) at 1200 mg Q2W. Due to the risk of infusion related reactions (IRR), the first dose of TOM was reduced to 720 mg split over 2 consecutive days and three cycles of TOM monotherapy were given before start of treatment with GAT. As this regimen was proven safe, no DLT was observed and the initial dose remained unchanged, the study was amended to enroll in an expansion phase (EP) 30 additional patients with refractory colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck and breast cancers. TOM and GAT were given at the same doses and GAT treatment started already one week after the first dose of the anti-EGFR antibody. Additionally investigator had the choice to use a commercial anti-EGFR antibody in place of TOM. Results: By the time of the final analysis in January 2021, 52 refractory patients were enrolled and 50 received at least one dose of both GAT and anti-EGFR antibodies. Panitumumab (PAN) was used in 9 CRC patients. Because of the difference in treatment schedule, results are summarized separately for the 20 and 30 patients in PP and EP. Overall, the combined treatment was well tolerated and no DLT was observed in the whole study, nor related SAE or death. There were no treatment emergent adverse events (TEAEs) leading to dose interruptions or reductions in the PP and 2/30 (6.7%) patients in EP stopped both TOM and GAT. 16 IRRs were reported in 8/20 (40%) PP patients, and 40 IRRs in 10 (33.3%) EP patients. Only one event of chills was severe and only 6 events were related to GAT in the EP, all others to TOM. Other frequent TEAEs were those commonly observed with anti-EGFR treatment such as skin toxicity in 17 (85%) PP and 26 (86.7%) EP patients and hypomagnesemia in 10 (50%) PP and 7 (23.3%) EP patients. Conclusions: Combination of TA-MUC1 and EGFR targeting antibody is safe and feasible. Future studies should test this combination together with chemotherapy Clinical trial information: NCT03360734.

Ten-year experience with rituximab for induction and maintenance therapy in patients with ANCA-associated systemic vasculitis

Rituximab (RTM), a monoclonal antibody against CD20+ receptors on the membrane of B-cells, is becoming increasingly important for the induction and maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (ANCA-SV). The challenge facing us is to optimize its efficacy, while limiting adverse events (AEs).Objective: to evaluate the efficacy and safety of RTM used for the induction and maintenance of remission in ANCA-SV on the basis of 10-year single-center experience.Patients and methods. The paper presents the authors’ own 10-year experience with RTM used for the induction and maintenance of remission in 103 patients with ANCA-SV, including granulomatosis with polyangiitis (GPA) (n=58), microscopic polyangiitis (MPA) (n=35), ANCA-positive eosinophilic granulomatosis with polyangiitis (EGPA) (n=4), and ANCA-negative EGPA (n=6). The duration of a follow-up after initiation of RTM treatment was more than a year (with the exception of death cases) and averaged 25 to 58 months in different ANCA-SV groups. The patients were monitored every 3 months. The intervals between repeated cycles were dependent on the time course of changes in clinical and laboratory parameters. The mean cumulative RTM dose exceeded 3 g; 75% of patients received repeated cycles of RMT usually at a cumulative dose of 0.5–1.0 g at a 4–12-month interval.Results and discussion. Repeated RTM cycles for ANCA-SV were highly effective; the clinical response rate was 97%, while 90–93% of patients with different types of ANCA-SV achieved complete clinical response. Despite the fact that the examined population included a high proportion of patients with a severe or refractory course of the disease; ANCA-SV patients showed 10% mortality rates during the entire follow-up period. Anti-B-cell therapy with RTM is of great importance in obtaining long-term optimal results, making it possible to improve ANCA-SV control and to minimize the cumulative dose of glucocorticoids. Since in ANCA-SV, the use of repeated cycles of RTM, including that at a reduced dose of 0.5 g, contributes to the higher efficiency of treatment and to the lower risk of relapse, it is advisable to perform long-term (≥2 years) RTM therapy, by controlling the parameters of clinical and immunological activities and the levels of circulating CD20+ B cells and serum immunoglobulins, deficiency of which can potentially increase the risk of infectious AEs. When planning RTM therapy, it is necessary to consider the specific features of the safety profile for individual nosological entities and to make a careful appropriate monitoring of ANCA-SV patients receiving RTM. The risk of late-onset neutropenia was highest in patients with all types of ANCA-SV (3–10%). Infections in patients with GPA and MPA constitute a substantial proportion (10–11%) in serious AEs. Management of EGPA patients requires alertness to the risk of infusion-related reactions, primarily bronchospasm.Conclusion. There is a need for further investigation of an anti-B-cell therapy strategy, including the efficacy and safety of RTM in ANCA-SV and for clarification of indications and optimal RTM treatment regimens.

Single Arm, Prospective, Open-Label Phase II Trial to Evaluate the Efficacy of Isatuximab in Patients with Monoclonal Gammopathy of Renal Significance

Background: Monoclonal gammopathy of renal significance (MGRS) is a monoclonal B cell disorder, not meeting the definition of lymphoma or myeloma, that produces monoclonal proteins which deposit in the kidneys. Permanent renal damage can occur either as a consequence of direct deposition of toxic proteins or by an induced inflammatory response. Due to the low burden of the plasma cell clone, patients do not otherwise qualify for potentially toxic anti-plasma cell treatments and treatment is generally based on consensus opinion. To date there are no clinical trials exploring treatment options. Isatuximab is a chimeric mouse/human IgG1k monoclonal antibody which targets CD38 on both malignant and normal plasma cells and exhibits it antitumor effects primarily by antibody-dependent cellular toxicity. Isatuximab has recently been shown to be an active drug in the treatment of multiple myeloma, with improvements seen in hematologic and renal markers, and has been shown to have manageable toxicity. Given the efficacy of isatuximab in multiple myeloma, we propose a trial evaluating isatuximab monotherapy to treat the small plasma cell clone in MGRS with the hopes of maximizing response and minimizing toxicity. Study Design and Methods: The primary objective of this study is to evaluate efficacy of isatuximab monotherapy in patients with MGRS in order to establish a standard of care treatment for patients with this disease. Adult patients with proteinuria of at least 1 gram in 24 hours and a histopathological diagnosis of MGRS on renal biopsy in the last 24 months will be eligible for the trial. Patients will be excluded if their estimated GFR is below 30 mL/min, they have multiple myeloma, high risk smoldering myeloma, other B cell neoplasm meeting criteria for treatment, concurrent diabetic nephropathy, or require dialysis. Patients will be screened for B cell disorders with bone marrow biopsy and aspirate, serum protein electrophoresis (SPEP) with immunofixation (IFE), 24-hour urine protein electrophoresis (UPEP), free light chain (FLC) testing and screening PET/CT at time of enrollment. Enrolled patients will be administered isatuximab 20 mg/kg IV weekly for 4 weeks and then will receive the same dose every 2 weeks thereafter for a total of 6 months. Patients may be continued on treatment following completion of the 6 months at the discretion of the provider. To reduce the risk of infusion related reactions, patients will receive premedications with corticosteroids, diphenhydramine, H2 blockade and acetaminophen at least 60 minutes prior to infusion. Patients will have repeat SPEP + IFE, 24-hour UPEP + IFE and FLC testing every 4 weeks. There will be an optional repeat kidney biopsy 9-12 months following treatment initiation to assess pathologic response in the kidneys. Statistical Methods: The study will be comprised of 20 patients being treated with isatuximab over a span of 24-30 months. Ten patients will be initiated on the therapy for a period of 6 months. Interim analysis will be done after these patients have completed all the treatment cycles. If 4 out of 10 patients show response in form of improved/stable renal function, the study will proceed to include next 10 patients. If &gt;50% of the first group of 10 patients show doubling of creatinine while on therapy, that would be considered as an indication to discontinue the therapy and the study due to drug toxicity. Endpoints: The primary endpoint will be efficacy as measured by renal response and hematologic response. Renal response will be measured by assessing the amount of proteinuria in a 24 hour urine sample. A sustained reduction in proteinuria by 30% from the patient's baseline amount of proteinuria with stable renal function (serum eGFR within 20% of baseline) will be considered a positive renal response. Hematologic response will be quantified per the 2016 International Myeloma Working Group (IMWG) uniform response criteria for multiple myeloma. An important secondary endpoint will be safety and will be analyzed from all patients who receive any study drug. Adverse events will be characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Other endpoints include time to dialysis and rate of minimal residual disease (MRD) negativity. Disclosures Lentzsch: Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; BMS: Consultancy; Proclara: Consultancy; Abbvie: Consultancy; Clinical Care Options: Speakers Bureau; Sanofi: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Honoraria; International Myeloma Foundation: Honoraria; Karyopharm: Research Funding; Columbia University: Patents &amp; Royalties: 11-1F4mAb as anti-amyloid strategy. Bhutani:Sanofi: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Our trial will be evaluating the efficacy of targeting CD38 on plasma cells with isatuximab in patients with monoclonal gammopathy of renal significance (MGRS). We will evaluate the effects of this drug on 24 hour proteinuria and hematologic response.

Ninety-minute daratumumab infusion is safe in multiple myeloma.

Background: Daratumumab, an anti-CD38 monoclonal antibody, was first approved for the treatment of relapsed and refractory multiple myeloma (MM) in December of 2015. The approved initial infusion lasts at least 6.5 hours, second infusion for 4.5 hours and all subsequent infusions over 3.5 hours. The risk of infusion related reactions (IRRs) is very low after the second infusion, and the prolonged continued infusion time results in long days for patients. Because of our success infusing other monoclonal antibodies over shorter times, such as rituximab (Dotson et al Support Care Cancer, 2016), we hypothesized that shortening the daratumumab infusion from 3.5 hours to 90 minutes beginning with the third infusion would not increase the incidence of IRRs. Methods: This is a single-center safety study of an accelerated daratumumab infusion in patients receiving standard of care daratumumab therapy. Patients were eligible once they received at least 2 prior doses of daratumumab, administered per standard prescribing information. Previous IRR was not an exclusion criterion. The accelerated infusion was calculated to deliver 20% of the dose over the first 30 minutes, then the remaining 80% over 60 minutes, resulting in an estimated 90 minute infusion (Table 1). Patients who tolerated the infusion well were allowed to continue the accelerated rate. Premedication regimens were allowed to be altered based on previous tolerability. Simon9s two-stage optimal design was utilized to design the study based on the incidence of grade 3 or above IRR. With 80% power the design allows 7 patients to be treated in the first stage, and if no patients experienced ≥ grade 3 IRR, an additional 21 patients would be treated. Out of all 28 patients, if 2 or more experienced ≥ grade 3 IRR, the regimen would be declared as too toxic. The protocol was approved by the cancer institutional review board. Results: Baseline characteristics are listed in Table 2. Twenty eight patients were treated with daratumumab utilizing the accelerated rate, 8 of which received the accelerated infusion with their third dose of daratumumab. The premedication regimen varied patient-to-patient and did not impact tolerability of the accelerated infusion. There were 5 patients who did not receive any steroid premedication and 3 who received reduced doses ( Conclusion: An accelerated infusion rate of daratumumab delivering 20% of the dose over 30 minutes and 80% over 60 minutes is feasible and well-tolerated in patients who have received 2 prior doses of daratumumab at standard infusion rates. Starting with the third dose of daratumumab therapy, the 90-minute infusion is now standard practice at our institution. Disclosures Hofmeister: Janssen: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Karyopharm: Research Funding; Celgene: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Thrassos: Honoraria, Membership on an entity9s Board of Directors or advisory committees.

Pegloticase: a guide to its use in treatment-refractory chronic gout in the EU

Intravenous pegloticase (KRYSTEXXA®), a recombinant polyethylene glycol-conjugated form of uricase (a uric acid-specific enzyme lacking in humans), is a novel approach to treating chronic gout refractory to conventional therapy. Pegloticase 8 mg every 2 weeks provides sustained reductions in plasma uric acid levels to less than the therapeutic target of 6 mg/dL (360 μmol/L) in a substantial proportion of patients with chronic refractory gout. The risk of infusion-related reactions can be minimized by following the recommended precautions, which include monitoring of serum uric acid levels.

Development of a single paediatric infliximab administration guideline

<h3>Objective</h3> Three separate infliximab prescribing and administration guidelines were being used within the paediatric departments at LTHT. Over a 6 month period this caused selection errors which resulted in a number of administration rate errors. The aim of this project was to develop a single paediatric infliximab administration guideline which could be used by all paediatric specialities at LTHT to help reduce prescribing and administration errors. <h3>Methods</h3> An extensive literature search was conducted to determine the ideal rate of administration of infliximab, the relationship between infusion reactions and infusion rate, and to establish what evidence there was for using a titrated infusion schedule when administering infliximab. Purposive sampling was utilised to contact 16 paediatric centres across the country to determine what guidelines and local practices they had in place for prescribing and administering infliximab. All LTHT infliximab guidelines and local guidelines from other paediatric centres were collated and critically appraised against the evidence base and discussed with stakeholders. <h3>Results</h3> Ten relevant papers were included in the literature review; four of these were review articles. None of the studies specified the rate at which the infliximab infusions were given. All the studies were clear that infliximab is associated with infusion related reactions including acute reactions, delayed hypersensitivity and immunogenicity. Although there does not appear to be a direct correlation between infusion rate and infusion related reactions, some authors suggested using a titrated infusion schedule to reduce the risk of infusion related reactions; previously recommended in the American datasheet for infliximab. Of 16 paediatric centres contacted 12 had infliximab guidelines in place; 6 of these were for rheumatology and 8 were for gastroenterology indications. Only three centres had guidelines in place for both gastroenterology and rheumatology. Nine out of the 12 centres used a titrated infusion schedule when administering infliximab. The hospital protocols that advocating using titrated infusion schedules were based on a clinical trial (Protocol C0168T32). One centre had an infliximab administration drug chart in use and three centres used specific infliximab administration record sheets. Local stakeholders were consulted with the evidence. It was decided a titrated infusion schedule would only be used for children with previous infusion reactions to infliximab. The format chosen for the guideline was a combined drug chart and guideline so that the guidance would be on hand as infliximab was prescribed and administered by the doctors and nurses. <h3>Conclusion</h3> An infliximab drug chart which doubles as a guideline has been developed and is used for all paediatric patients receiving infliximab. We hope a single guideline will aid prescribing and reduce administration rate errors. An audit to evaluate the guideline and determine whether it has resulted in reduced errors is to be conducted shortly.

411: Rituximab Monitoring in Hematopoietic Stem Cell Transplant: How much is Necessary?

Background: Rituximab, an uncongugated monoclonal antibody that reacts with the CD20 molecule present on most malignant B-cells, is standard treatment for patients with lymphoma. Most rituximab infusions are well tolerated with a mild infusion related symptom complex (fever, chills/rigors) usually occurring within 1 hour after initiation. Severe infusion related reactions (IRR), such as bronchospasm and hypotension, occur infrequently; most often within 2 hours after initiating the first dose. Reactions are caused by cytokine release associated with high numbers of circulating tumor cells. Incidence of IRRs decreases markedly with subsequent infusions. At a university based comprehensive cancer center, controlled trials using rituximab for treatment of NHL are underway in hematopoietic stem cell transplant patients to determine optimal dosing and scheduling. Patients participating in these trials are heavily pretreated with rituximab, and are in partial or complete remission before admission for transplant. Based on phase I and II trials, frequent vital sign (VS) monitoring and concurrent administration of normal saline are recommended. Current organizational clinical practice standards require between 10–16 sets of VS over 5–6 hours for average rituximab infusions; interfering with patient comfort and requiring significant nursing time. Purpose: To determine the frequency and risk of IRRs in patients admitted for transplant and an optimal vital sign monitoring schedule. Method: A nurse initiated, IRB-approved, retrospective review of 200 medical records was conducted. Data analysis is in progress to determine IRR frequency, identify patients at high risk for reactions, and determine an appropriate VS schedule. Results: Study findings will be reported.

A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations

Objective: A systematic review was performed to compare the effectiveness and tolerability of lipid-based amphotericin B (AmB) formulations and conventional AmB in the treatment of systemic fungal infections. Methods: The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases. Search terms included: amphotericin, liposom ∗, lipid ∗, colloid ∗, antifungal agents , and mycoses. Studies were selected according to predetermined criteria. The outcome measures reviewed were efficacy, mortality, renal toxicity, and infusion-related reactions. Meta-analyses and number-needed-to-treat (NNT) analyses were performed. Results: Seven studies (8 publications) met the entry criteria. Meta-analysis showed that lipid-based formulations significantly reduced all-cause mortality risk by an estimated 28% compared with conventional AmB (odds ratio [OR], 0.72; 95% CI, 0.54 to 0.97). There was no significant difference in efficacy between the lipid-based formulations and conventional AmB (OR, 1.21; 95% CI, 0.98 to 1.49). AmB lipid complex (ABLC) and liposomal AmB (L-AmB) significantly reduced the risk of doubling serum creatinine by an estimated 58% (OR, 0.42; 95% CI, 0.33 to 0.54). There was no significant reduction in risk of infusion-related reactions with lipid-based formulations, although this was difficult to interpret given the lack of consistent control of confounding factors. Comparing the lipid-based formulations with conventional AmB, the overall NNT to prevent 1 death was 31. The NNT to prevent a doubling of serum creatinine for both ABLC and L-AmB compared with conventional AmB was 6. Conclusions: This study demonstrates advantages with lipid-based formulations over conventional AmB in terms of reduced risk of mortality and renal toxicity. Future trials in patients with proven fungal infection should control for factors such as premedication, infusion rates, fluid preloading, sodium/potassium supplementation, and concomitant medication.