Sequential high-dose methotrexate and cytarabine administration improves outcomes in real-world patients with primary central nervous system lymphoma: A report from the Australasian Lymphoma Alliance.

Background: Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods: We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B-cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high-dose methotrexate (HD-MTX) containing chemotherapy regimens: MPV/Ara-C (HD-MTX, procarbazine, and vincristine, followed by cytarabine [Ara-C]) (n = 94, 50%), MATRix (HD-MTX, Ara-C, thiotepa, and rituximab) (n = 19, 10%), HD-MTX/Ara-C (n = 31, 16%), HD-MTX monotherapy (n = 35, 18%) and MBVP (HD-MTX, carmustine, teniposide, prednisolone) (n = 11, 6%). Results: Cumulative median HD-MTX and Ara-C doses were 17 g/m2 (range: 1-64 g/m2) and 12 g/m2 (0-32 g/m2) respectively. Using 14 g/m2 as the reference dose, the median HD-MTX relative dose intensity (HD-MTX-RDI) was 1.25 (0.27-4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD-MTX. At a median follow-up of 3.41 years (0.06-9.42), progression-free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara-C cohort (2-year PFS 74%, 2-year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara-C administration and HD-MTX-RDI > 0.75 were associated with longer PFS and OS. Conclusion: Sequential, response-adapted approaches can improve outcomes, even in older patients who are ineligible for a high-intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.

Antenatal haemoglobinopathy screening - Experiences of a large Australian Centre.

BACKGROUND: Antenatal screening is vital to identifying couples at risk of having children with a clinically significant haemoglobinopathy. In Australia, immigration is increasing carrier incidence. METHODS: A retrospective analysis was performed of full blood count, high-performance liquid chromatography and haemoglobin electrophoresis of women and their partners who underwent antenatal haemoglobinopathy screening over three years at a major NSW laboratory. Genetic testing results were included where available. RESULTS: One thousand six hundred and twenty-eight women and 729 male partners were screened at a median gestation of 14 weeks. 8.2% of women had a clinically significant result, with a median 16-day interval to partner testing. In 35% of couples screened simultaneously, the partner did not require testing. Genetic confirmatory testing was performed in 65% of high risk couples. CONCLUSION: There was a significant delay to antenatal haemoglobinopathy screening for mothers, limiting time for genetic diagnosis, prenatal diagnosis and management of affected pregnancies. Screening should be performed earlier. Simultaneous couple testing is not cost-effective.

Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer.

INTRODUCTION: Lung cancer is a leading cause of cancer mortality worldwide. Non-invasively collected biofluids such as exhaled breath condensate (EBC) present a potential sampling medium to detect and study pathological changes implicated in tumourigenesis. Mitochondrial DNA changes have been implicated in the carcinogenesis process. Consequently, the detection of mitochondrial changes in EBC could expand our understanding of lung carcinogenesis as well as identifying specific markers for future studies. METHODS: EBC and saliva was collected from newly diagnosed subjects with lung cancer and control subjects in a cross-sectional study. The EBC and saliva was analysed for mitochondrial DNA D-loop changes using a PCR sequencing approach. The sequences obtained were compared to paired salivary DNA and the revised Cambridge Reference Sequence (rCRS) to identify somatic mutations, and quantitative and qualitative differences in mutations were analysed between groups. RESULTS: A total of 25 subjects (9 NSCLC patients, 10 smokers/ex-smokers and 6 non-smokers) were recruited. A significantly elevated D-loop mutation rate in the lung cancer group compared to the control groups was present (7 vs 3.5 for smokers/ex-smokers, and 7 vs. 4 for non-smokers, p = 0.034). The recognised mutation T16217C showed specificity for lung cancer. CONCLUSIONS: Mitochondrial DNA mutations are more common in the EBC of patients with lung cancer. This suggests that these processes are associated with the carcinogenesis of lung cancer and may be a marker of the disease.