Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Adequate asparagine depletion is believed to be an important factor in achieving optimal therapeutic outcomes. Measurement of asparaginase activity allows practitioners to evaluate the potential effectiveness of therapy in real time. Asparaginase activity levels can be used to identify patients with silent inactivation and modify therapy in these patients. Patients with silent inactivation to asparaginase who are switched to therapy with an immunologically distinct asparaginase exhibit outcomes similar to patients who never developed silent inactivation. Despite these benefits, there exists no universally agreed-upon guideline for treatment adjustments based on asparaginase activity levels. The goal of this manuscript is to review the clinical evidence linking asparaginase activity levels to outcomes in patients with ALL and to provide an overview of how asparaginase activity levels may be used to guide treatment.

The posaconazole extended release tablet formulation was developed to improve bioavailability relative to the oral suspension. Therapeutic drug monitoring has been used to optimise posaconazole dosing to achieve a target trough level ≥0.7 μg ml(-1). We retrospectively evaluated 28 patients with haematological malignancies who received posaconazole tablets for antifungal prophylaxis. Posaconazole serum trough levels were obtained 5 days after initiation of therapy. Mean trough level was 1.19 ± 0.63 μg ml(-1), and 71% achieved a trough level ≥0.7 μg ml(-1). Diarrhoea was associated with lower mean trough levels (0.65 ± 0.08 μg ml(-1) vs. 1.31 ± 0.13 μg ml(-1)), P = 0.002. Mean trough levels were lower in patients ≥90 kg (0.74 ± 0.09 μg ml(-1)) vs. <90 kg (1.32 ± 0.14 μg ml(-1)), P = 0.002 and in patients with body mass index (BMI) ≥30 (0.89 ± 0.13 μg ml(-1)) vs. BMI <30 (1.29 ± 0.14 μg ml(-1)), P = 0.05. Posaconazole delayed release tablets attain appropriate trough levels in most patients, but patients with a higher weight and those experiencing diarrhoea are more likely to have lower levels.

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Haematology patients exhibit a higher rate of rCDI than general hospitalized patients. Utilization of this multivariable model to guide index CDI therapy at index may help to decrease the rCDI and prevent delays or interruptions in chemotherapy.

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered.

OBJECTIVE:To review evidence for the use of intrathecal rituximab and trastuzumab in the management of leptomeningeal carcinomatosis.