Pneumocystis jirovecii pneumonia in paediatric acute lymphoblastic leukaemia: A report from the multi-international clinical trial AIEOP-BFM ALL 2009.

Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well-defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi-international trial AIEOP-BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long-term impact of the infection is unclear.

Prospective use of molecular minimal residual disease for risk stratification in children and adolescents with acute lymphoblastic leukemia : Long-term results of the AIEOP-BFM ALL 2000 trial in Austria.

Since 1979 Austrian children and adolescents with acute lymphoblastic leukemia (ALL) have been treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group. The Associazione Italiana di Ematologia e Oncologia Pediatrica and BFM (AIEOP-BFM) ALL 2000 study was designed to prospectively study patient stratification into three risk groups using minimal residual disease (MRD) on two time points during the patient's early disease course. The MRD levels were monitored by detection of clone-specific rearrangements of the immunoglobulin and T­cell receptor genes applying a quantitative polymerase chain reaction-based technique. The 7­year event-free survival (EFS) and overall survival rates for all 608 Austrian patients treated between June 1999 and December 2009 within the AIEOP-BFM 2000 study were 84 ± 2% and 91 ± 1%, respectively, with a median observation time of 6.58 years. Event-free survival for patients with precursor B­cell and T­cell ALL were 84 ± 2% (n = 521) and 84 ± 4% (n = 87; p = 0.460), respectively. The MRD assessment was feasible in 94% of the patients and allowed the definition of precursor B­cell ALL patients with a low, intermediate or high risk of relapse even on top of clinically relevant subgroups. A similar finding with respect to MRD relevance in T­ALL patients was not possible due to the small number of patients and events. Since this pivotal international AIEOP-BFM ALL 2000 trial, molecular response to treatment has been continuously used with additional refinements to stratify patients into different risk groups in all successive trials of the AIEOP-BFM ALL study group.

Second malignant neoplasms after treatment of 1487 children and adolescents with acute lymphoblastic leukemia-A population-based analysis of the Austrian ALL-BFM Study Group.

Second malignant neoplasms (SMN) after primary childhood acute lymphoblastic leukemia (ALL) are rare. Among 1487 ALL patients diagnosed between 1981 and 2010 in Austria, the 10-year cumulative incidence of an SMN was 1.1% ± 0.3%. There was no difference in the 10-year incidence of SMNs with regard to diagnostic-, response- and therapy-related ALL characteristics except for a significantly higher incidence in patients with leukocytes ≥50.0 G/L at ALL diagnosis (2.1% ± 1.0% vs. 0% for 20.0-50.0 G/L, and 1.0% ± 0.3% for < 20.0 G/L; p = 0.033). Notably, there was no significant difference in the incidence of SMNs between patients with or without cranial radiotherapy (1.2% ± 0.5% vs. 0.8% ± 0.3%; p = 0.295). Future strategies must decrease the incidence of SMNs, as this event still leads to death in one-third (7/19) of the patients.

First finding of tiemannite, HgSe, in human bladder stones: An electron microprobe study.

Human bladder stones, surgically removed from a 4 years old boy, were studied by X-ray diffraction (XRD) and by electron microprobe analyses (EPMA). XRD data show that the bladder stones are mainly composed of struvite with minor apatite. Tiny particles, <10 µm in size, composed of mercury (Hg) and selenium (Se) were found using scanning electron microscopy (SEM) and quantitative analysis by wave-length dispersive system (WDS). On the basis of their composition, the particles consist of tiemannite, a rare mineral with the ideal formula HgSe. The young patient was not exposed to relevant mercury contamination and has no teeth fillings of amalgam. Although this observation is not conclusive, we suggest that Hg was introduced as methylmercury by food. The discovered tiemannite can be classified as endogenous mineral, i.e., directly precipitated from the same fluids that formed the host bladder stones. This assumption is supported by the fact that tiemannite and struvite can crystallize at the same temperature and pH values. As proposed for the formation of tiemannite previously reported in the liver of cetaceans, we suggest that the tiemannite in the human body represents a probable product of demethylation of Hg. In this contribution, we suggest that Hg and Se were initially collected by urine in the human body and finally precipitated to form tiemannite under appropriate chemical-physical conditions together with the formation of the host bladder stone. This observation suggests that the precipitation and accumulation of metals, including Hg and Se, in the human body can be considered a physiological response to eliminate part of these trace elements, thus enabling detoxification.

Metals in Human Gall, Bladder, and Kidney Stones Based on an Electron Microprobe Investigation.

Several particles of copper accompanied by a few particles of nickel, lead, and a compound composed of selenium containing minor Ni, Si, Cu, and Co were found in human gall, kidney, and bladder stones. The investigated particles occur as tiny grains, <10 µm in size, that are irregularly dispersed in the stones. Therefore, they were studied by scanning electron microscopy and qualitatively analyzed by energy dispersive system. One grain of copper contained a small amount of Ni and Zn, and some grains of nickel proved to contain Cr as trace element. Most of the discovered metals formed a single-phase grain. However, a few grains found in two gallstones were associated with inclusions of calcium and apatite. Based on the results presented in this contribution, we argue that most of the studied metals can be classified as endogenous particles, i.e., directly precipitated from the same fluids that formed their host human stones. This observation suggests that the precipitation and accumulation of metals in some human stones can be considered an efficient way to eliminate them from the human body.

Recurrent Pott's puffy tumor - atypical presentation of a rare disorder.

We report the case of a 14-year-old girl who presented with an 8-week history of unilateral pansinusitis. In the course of the disease a right-side frontal swelling was observed, which disappeared following antibiotic treatment. Four weeks later, however, the swelling reappeared and was now diagnosed as recurrent Pott's puffy tumor. Interestingly, C-reactive protein levels were in the normal range throughout. Following functional endoscopic frontal sinusotomy, antibiotic treatment with ceftriaxone was administered over 3 weeks and led to complete remission of the lesion. Pott's puffy tumor is a subperiostal abscess of the frontal bone, usually presenting as localized swelling of the soft tissue in the overlying region of the forehead, and is associated with localized osteomyelitis and occasionally with intracranial epidural abscess. The entity has been known since 1768, although recurrent cases with normal inflammation parameters have not been published previously.

Treatment for soft tissue sarcoma in childhood and adolescence. Austrian results within the CWS 96 study.

OBJECTIVE: The aim of the CWS 96 Study was to achieve an optimal treatment in children and adolescents with soft tissue sarcoma (STS) implementing a further refinement of risk-adapted allocation to chemotherapy, surgery and radiotherapy. METHODS: Treatment stratification was based on tumour histology, TNM status, postsurgical stage, localisation and age. Local tumour control was ensured by surgery and risk-adapted radiotherapy. RESULTS: From 1995 to 2002, 89 patients were registered in Austria. The 3-year event-free survival (EFS) and overall survival rates (OS) were 63% +/- 6% and 71% +/- 6%, respectively. 59/89 patients had localised RMS-like (rhabdomayosarcoma) STS (EFS 73% +/- 7%), 14 had localised NON-RMS STS (EFS 54% +/- 16%) and 15 patients had metastatic disease at diagnosis (EFS 33% +/- 12%), 1 patient had fibromatosis. The EFS rates at 3 years in patients with localised RMS-like tumours according to risk group were 92% +/- 8% for low and standard risk (12 patients) and 67% +/- 8% for high risk (47 patients). Favourable primary tumour sites of nonmetastatic RMS-like STS i.e. orbit, head/neck nonparameningeal or genitourinary non-bladder/prostate were diagnosed in 15 patients (1/15 patients died). In 44 patients with unfavourable localisation such as parameningeal, genitourinary bladder/prostate, extremity and others, 7 deceased. The 3 year EFS according to histology in patients with RMS-like STS was 61% +/- 11% for RME (embryonal RMS ) (28 patients) and 71% +/- 15% for RMA (alveolar RMS) (10 patients). The most common treatment failure was local relapse occurring in 21% of patients in the high-risk group. CONCLUSION: Risk-adapted individualisation of treatment led to a reduction of chemotherapy in the low and standard risk group without compromising survival. The outcome of RME and RMA was similar in this cohort of patients. These preliminary results after a median observation time of 2.5 years confirm the CWS 96 strategy.