Comprehensive geriatric assessment is useful in an elderly Australian population with diffuse large B-cell lymphoma receiving rituximab-chemotherapy combinations.

Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy-associated toxicities. We describe the morbidity of rituximab-chemotherapy combinations among 205 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients aged ≥60 years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively-assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy-three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166 (23%) had chemotherapy delays and 26/198 (13%) ceased therapy early. CGA was associated with pre-emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three-year overall survival (OS) of CGA-fit, CGA-unfit and CGA-frail patients was 82%, 60% and 53%, respectively. Three-year progression-free survival (PFS) of CGA-fit, CGA-unfit and CGA-frail patients was 66%, 58% and 46%, respectively. OS of CGA-fit patients was not statistically different from CGA-unfit patients, but was superior to CGA-frail patients (hazard ratio 2·892, 95% confidence interval 1·275-6·559, P = 0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA-adapted treatment strategies minimize morbidity and improves survival.

Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit.

OBJECTIVES: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD. METHODS: A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective. RESULTS: Ninety-eight patients were included in the audit; 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal amphotericin B and an azole. Five proven/probable and six possible IFD cases were identified. Proven/probable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven/probable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4%; P = 0.024). For every five patients receiving PAP, one proven/probable IFD case would be prevented. Proven/probable IFD was associated with an additional median cost of 121,520 Australian dollars (95% CI: 90,781-180,141 Australian dollars; P < 0.001) compared with patients without IFD. CONCLUSIONS: This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk.

Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy.

BACKGROUND: Fluconazole, posaconazole and voriconazole are used prophylactically in patients with acute myeloid leukaemia (AML). This study evaluated the clinical and economic outcomes of these agents when used in AML patients undergoing consolidation chemotherapy. METHODS: A retrospective chart review (2003-10) of AML patients receiving consolidation chemotherapy was performed. Patients were followed through their first cycle of consolidation chemotherapy. Antifungal prescribing patterns, clinical outcomes and resource consumptions were recorded. A decision analytical model was developed to depict the downstream consequences of using each antifungal agent, with success defined as completion of the designated course of initial antifungal prophylaxis without developing invasive fungal disease (IFD). Cost-effectiveness and sensitivity analyses were performed. RESULTS: A total of 106 consecutive patients were analysed. Baseline characteristics and predisposing factors for IFD were comparable between groups. Three IFDs (one proven, one probable and one suspected) occurred, all in the posaconazole group. Patients receiving posaconazole had the highest rate of intolerance requiring drug cessation (13% versus 7% in each of the fluconazole and voriconazole groups). Fluconazole conferred overall savings per patient of 26% over posaconazole and 13% over voriconazole. Monte Carlo simulation demonstrated a mean cost saving with fluconazole of AU$8430 per patient (95% CI AU$5803-AU$11 054) versus posaconazole and AU$3681 per patient (95% CI AU$990-AU$6319) versus voriconazole. One-way sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This is the first study to show that, in the setting of consolidation therapy for AML, fluconazole is the most cost-effective approach to antifungal prophylaxis compared with posaconazole or voriconazole.

The impact of a regular erythrocytapheresis programme on the acute and chronic complications of sickle cell disease in adults.

Thirteen adult patients aged 22-63 (median 30) years with sickle cell disease (SCD) were enrolled in a regular erythrocytapheresis (ECP) programme at a single institution between December 1998 and November 2008. The indications for enrolment were recurrent painful crises (PC), acute chest syndrome (ACS), silent cortical ischaemia, pulmonary hypertension, multi-organ crises and pregnancy. Endpoints retrospectively evaluated included the incidence of SCD-related acute events requiring hospitalization following and prior to regular ECP, the development of new and progression of pre-existing related end-organ damage, the effectiveness in reducing HbS levels acutely and prior to the next exchange and the transfusion-related complications. Sixteen acute sickle-related events occurred in five patients in 846 months of patient follow-up. In all patients with reliable data available pre-ECP, the frequency of such events was reduced following commencing regular ECP. No patient experienced stroke, multi-organ crises or developed new and/or progression of end-organ dysfunction. Regular ECP reduced HbS levels to the target of <30% immediately post-exchange. Alloimmunization rates were comparable to the literature and ECP was effective in preventing progressive iron overload. Regular ECP was demonstrated to be an effective, well-tolerated therapy for both acute and chronic complications of SCD in adults.

Pharmacoeconomic evaluation of voriconazole versus posaconazole for antifungal prophylaxis in acute myeloid leukaemia.

BACKGROUND: Voriconazole and posaconazole are used prophylactically against invasive fungal infection (IFI) in patients with acute myeloid leukaemia (AML). The current study attempted to evaluate the economics of voriconazole versus posaconazole for prophylaxis in AML. METHODS: A 6 year (2003-09) retrospective chart review of AML patients was performed at a major Australian tertiary hospital. Patients were followed through the induction stage of chemotherapy, estimating outcome probabilities and prescribing patterns of antifungal prophylaxis. Cost inputs were obtained from the latest Australian sources. A decision analytical model was developed to depict options and consequences involved in the prophylaxis, including success, survival, possible and proven IFIs, and discontinuations due to intolerance. A cost-benefit analysis and an uncertainty study through sensitivity analyses were performed. RESULTS: Fifty-six and 38 patients were evaluated in the voriconazole and posaconazole groups, respectively. Baseline demographic characteristics were not significantly different between the study cohorts. Posaconazole was associated with an overall cost saving of AU$17,458 (29%) per patient over voriconazole. The posaconazole group was associated with lower rate of death, as well as lower probability of discontinuation because of possible infections and intolerance to oral administration. The voriconazole group was associated with fewer proven infections. As per sensitivity analyses, results were highly robust over variations in all costs and probabilities in the model. Monte Carlo simulation suggested a 91.6% chance for posaconazole to cost less than voriconazole. CONCLUSIONS: This is the first economic evaluation of voriconazole versus posaconazole; where posaconazole appears to be more cost-beneficial than voriconazole as antifungal prophylaxis in AML.