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Zusammenfassung Chronische Verlaufsformen pulmonaler Aspergillosen (CPA) treten bei Patienten unterschiedlicher Disziplinen als seltene Komplikation leichter bis mittelschwerer Immunsuppression oder chronischer Lungenparenchymveranderung auf. Durch unspezifische klinische Auspragung und protrahierten Verlauf stellen sie fur den behandelnden Arzt eine diagnostische und therapeutische Herausforderung dar. Die Diagnosestellung stutzt sich im Wesentlichen auf CT-radiologische Kennzeichen und den serologischen Nachweis von Prazipitinen. Therapeutisch sind in variabler Frequenz und Dauer antimykotische Therapien notwendig. Eine Resektion wird lediglich fur das simple Aspergillom empfohlen. In den ersten Jahren nach Diagnosestellung ist ein gutes Ansprechen auf antimykotische Therapie beschrieben. Die Langzeitprognose ist ungewiss. Wir geben einen uberblick uber Epidemiologie, Diagnose und Management der CPA. Die Diversitat dieses Krankheitsbildes wird durch vier Fallbeispiele illustriert. Abstract Chronic pulmonary aspergillosis (CPA) is a rare complication in patients with either mild immunosuppression or various pulmonary diseases. Diagnosis and therapy are challenging because of unspecific symptoms like productive cough, weight loss, fever and haemoptysis. Differential diagnoses are manifold, and CPA is characterized by findings in chest CT and serologic proof of precipitins. Surgery is only recommended for simple aspergillomas. Recurrent prolonged courses of antifungal treatment yield satisfactory short-term outcome, but long-term prognosis is uncertain. We provide an overview of the literature and present four cases to illustrate disease diversity.

BACKGROUND: Chemotherapy for primary central nervous system lymphoma (PCNSL) is based on methotrexate (MTX), which interferes with both nucleic acid synthesis and methionine metabolism. We have reported previously that genetic variants with influence on methionine metabolism are associated with MTX side effects, that is, the occurrence of white matter lesions as a sign of MTX neurotoxicity. Here, we investigated whether such variants are associated with MTX efficacy in terms of overall survival in MTX-treated PCNSL patients. METHODS: We analysed seven genetic variants influencing methionine metabolism in 68 PCNSL patients treated with systemic and facultative intraventricular MTX-based polychemotherapy (Bonn protocol). RESULTS: Median age at diagnosis was 59 years (range: 28-77), 32 patients were female. Younger age (Wald = 8.9; P = 0.003) and the wild-type C (CC) allele of the genotype transcobalamin c (Tc2). 776C>G (Wald = 6.7; P = 0.010) were associated with longer overall survival in a multivariate COX regression analysis. CONCLUSION: This observation suggests that the missense variant Tc2. 776C>G influences both neurotoxicity and efficacy of MTX in the Bonn PCNSL protocol. British Journal of Cancer (2012) 107, 1840-1843. doi:10.1038/bjc.2012.476 www.bjcancer.com Published online 25 October 2012 (C) 2012 Cancer Research UK

Background:Chemotherapy for primary central nervous system lymphoma (PCNSL) is based on methotrexate (MTX), which interferes with both nucleic acid synthesis and methionine metabolism. We have reported previously that genetic variants with influence on methionine metabolism are associated with MTX side effects, that is, the occurrence of white matter lesions as a sign of MTX neurotoxicity. Here, we investigated whether such variants are associated with MTX efficacy in terms of overall survival in MTX-treated PCNSL patients.Methods:We analysed seven genetic variants influencing methionine metabolism in 68 PCNSL patients treated with systemic and facultative intraventricular MTX-based polychemotherapy (Bonn protocol).Results:Median age at diagnosis was 59 years (range: 28-77), 32 patients were female. Younger age (Wald=8.9; P=0.003) and the wild-type C (CC) allele of the genotype transcobalamin c (Tc2). 776C>G (Wald=6.7; P=0.010) were associated with longer overall survival in a multivariate COX regression analysis.Conclusion:This observation suggests that the missense variant Tc2. 776C>G influences both neurotoxicity and efficacy of MTX in the Bonn PCNSL protocol.

Background A systemic and intraventricular polychemotherapy regimen (the Bonn protocol) without radiotherapy resulted in durable responses in 75% of patients <60 years with primary CNS lymphoma (PCNSL), but was complicated by a high rate of Ommaya reservoir infections. Here, the efficacy and toxicity of this regimen without intraventricular treatment was evaluated in PCNSL. Patients and methods From August 2003 to November 2005, 18 patients with PCNSL <60 years (median age, 53 years) were treated in a phase II trial with a high-dose methotrexate (MTX; cycles 1, 2, 4 and 5) and cytarabine (Ara-C; cycles 3 and 6) based systemic therapy including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide. Results Study accrual was prematurely stopped in November 2005 due to a high rate of early relapses. Seventeen of 18 patients were assessable for response: nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu) and two (12%) partial response (PR); four (24%) showed progressive disease (PD). One treatment was stopped due to toxicity. Median follow-up was 23 months, median response duration was only 10 months in responding patients, and median time to treatment failure (TTF) was 8 months in the whole group. Median overall survival (OS) has not been reached. Systemic toxicity was mainly hematologic. Conclusions In PCNSL patients <60 years, polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with intraventricular treatment.