Nanox: a miniature mechanical stress rig designed for near-field X-ray diffraction imaging techniques.

Multi-modal characterization of polycrystalline materials by combined use of three-dimensional (3D) X-ray diffraction and imaging techniques may be considered as the 3D equivalent of surface studies in the electron microscope combining diffraction and other imaging modalities. Since acquisition times at synchrotron sources are nowadays compatible with four-dimensional (time lapse) studies, suitable mechanical testing devices are needed which enable switching between these different imaging modalities over the course of a mechanical test. Here a specifically designed tensile device, fulfilling severe space constraints and permitting to switch between X-ray (holo)tomography, diffraction contrast tomography and topotomography, is presented. As a proof of concept the 3D characterization of an Al-Li alloy multicrystal by means of diffraction contrast tomography is presented, followed by repeated topotomography characterization of one selected grain at increasing levels of deformation. Signatures of slip bands and sudden lattice rotations inside the grain have been shown by means of in situ topography carried out during the load ramps, and diffraction spot peak broadening has been monitored throughout the experiment.

[Biosimilars in oncology: a therapeutic alternative to the reference products?] / Biosimilars in der Onkologie: Eine therapeutische Alternative zu Referenzarzneimitteln?

Biosimilar medicinal products (biosimilars) have been available in Europe for 10 years, allowing a wide use particularly in oncology. Biosimilars are being developed and approved by means of scientifically sound principles to assure close similarity with the reference products with regard to quality, efficacy, and safety. The scientific principles for establishing biosimilarity are the same as those for demonstrating comparability after a change in the manufacturing process of an already licensed biological. Nevertheless, many clinicians voiced concerns about biosimilars related to their pharmaceutical quality, efficacy (particularly in extrapolated indications), safety (especially immunogenicity), and interchangeability with the originator product. The availability of biosimilars would strengthen the economic competition on the pharmaceutical market, provide opportunities to improve healthcare access, and contribute to the financial sustainability of European healthcare systems. Biosimilars can be considered therapeutic alternatives to the reference product. To date, no data has been published revealing any disadvantages of the biosimilars' use. This article aims to acquaint clinicians, particularly oncologists and haematologists, with the biosimilar concept as they are going to be confronted with a constantly increasing number of biosimilars due to patent expirations in the near future. Furthermore, it provides information on scientific principles guiding biosimilar development and regulatory requirements. This should minimise unfounded fears and concerns among clinicians. Additionally, we provide information on the interchangeability between originator products and biosimilars to assist clinicians in making evidence-based, appropriate, and cost-effective treatment choices for their patients.

Cold neutron diffraction contrast tomography of polycrystalline material.

Traditional neutron imaging is based on the attenuation of a neutron beam through scattering and absorption upon traversing a sample of interest. It offers insight into the sample's material distribution at high spatial resolution in a non-destructive way. In this work, it is expanded to include the diffracted neutrons that were ignored so far and obtain a crystallographic distribution (grain mapping). Samples are rotated in a cold neutron beam of limited wavelength band. Projections of the crystallites formed by the neutrons they diffract are captured on a two dimensional imaging detector. Their positions on the detector reveal their orientation whereas the projections themselves are used to reconstruct the shape of the grains. Indebted to established synchrotron diffraction contrast tomography, this 'cold neutron diffraction contrast tomography' is performed on recrystallized aluminium for experimental comparison between both. Differences between set-up and method are discussed, followed by the application range in terms of sample properties (crystallite size and number, mosaicity and typical materials). Neutron diffraction contrast tomography allows to study large grains in bulky metallic structures.

[Perioperative management of patients with rheumatoid arthritis]. / Perioperatives Management von Patienten mit rheumatoider Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint and systemic manifestations. As the prevalence in the adult population is approximately 1 %, anesthesia management in patients with RA has to be performed on a regular basis. Besides elective orthopedic surgery, e.g. surgery of the cervical spine, all other types of planned and emergency surgery should also be anticipated. Administering anesthesia to a patient with RA can be challenging not only due to a higher incidence of difficult intubation but also because of various organ manifestations as well as an elevated cardiovascular risk. Furthermore, possible complications should be considered in patients with chronic medication, particularly in patients treated with immunomodulating drugs. Therefore, a careful preoperative evaluation, preparation for possible difficult airway management and a selective anesthesia management in patients with RA can prevent possible complications.

Storm-induced transfer of particulate trace metals to the deep-sea in the Gulf of Lion (NW Mediterranean Sea).

In order to calculate budgets of particulate matter and sediment-bound contaminants leaving the continental shelf of the Gulf of Lion (GoL), settling particles were collected in March 2011 during a major storm, using sediment traps. The collecting devices were deployed in the Cap de Creus submarine canyon, which represents the main export route. Particulate matter samples were analyzed to obtain mass fluxes and contents in organic carbon, Al, Cr, Co, Ni, Cu, Zn, Cd, Pb and La, Nd and Sm. The natural or anthropogenic origin of trace metals was assessed using enrichment factors (EFs). Results are that Zn, Cu and Pb appeared to be of anthropogenic origin, whereas Ni, Co and Cr appeared to be strictly natural. The anthropogenic contribution of all elements (except Cd) was refined by acid-leaching (HCl 1 N) techniques, confirming that Zn, Cu and Pb are the elements that are the most enriched. However, although those elements are highly labile (59-77%), they do not reflect severe enrichment (EFs <4). Most particles originate from the Rhone River. This has been confirmed by two different tracing procedures using rare earth elements ratios and concentrations of acid-leaching residual trace metals. Our results hence indicate that even in this western extremity of the GoL, storm events mainly export Rhone-derived particles via the Cap de Creus submarine canyons to the deep-sea environments. This export of material is significant as it represents about a third of the annual PTM input from the Rhone River.

Comparative phylobiomic analysis of the bacterial community of water kefir by 16S rRNA gene amplicon sequencing and ARDRA analysis.

AIMS: The aim of this study was to analyse the bacterial microbiota of water kefir using culture-independent methods. METHODS AND RESULTS: We compared four water kefirs of different origins using 16S rDNA amplicon sequencing and ARDRA. The microbiota consisted of different proportions of the genera Lactobacillus (Lact.), Leuconostoc (Leuc.), Acetobacter (Acet.) and Gluconobacter. Surprisingly, varying but consistently high numbers of sequences representing members of the genus Bifidobacterium (Bif.) were found in all kefirs. Whereas part of the bifidobacterial sequences could be assigned to Bifidobacterium psychraerophilum, a majority of sequences identical to each other could not be assigned to any known species. A nearly full-length sequence of the latter exhibited a beyond-species similarity (96.4%) with the sequence from the closest relative species Bif. psychraerophilum. A Bifidobacterium-specific ARDRA analysis reflected the abundance of the novel Bifidobacterium species by revealing its unique MboI restriction profile. Attempts to isolate the bifidobacteria were successful for Bif. psychraerophilum only. CONCLUSIONS: The complexity of the water kefir microbiota has been underestimated in previously studies. The occurrence of bifidobacteria as part of the consortium is novel. SIGNIFICANCE AND IMPACT OF THE STUDY: These data give new insights into the understanding of the complexity of food fermentations and underline the need for approaches detecting noncultivable organisms.

Lineage classification of childhood acute lymphoblastic leukemia according to the EGIL recommendations: results of the ALL-BFM 2000 trial.

BACKGROUND: Flow cytometry immunophenotyping (FCM) is an undispensable tool for the diagnosis and for the treatment stratification of childhood acute lymphoblastic leukemia. The correlation of the EGIL-classification with prognostically relevant parameters like age, prednisone response and risk group is analyzed. PATIENTS: Between March 2000 and June 2009 12 patients less than 1 year of age, 1 836 patients with 1 to less than 6 years, 620 patients with 6 to less than 10 years, 615 patients with 10 to less than 15 years and 275 patients with 15 to less than 19 years were analyzed with a comprehensive 4-color antibody panel and classified according to the EGIL recommendations. METHODS: Bone marrow or peripheral blood mononuclear cells were isolated by ficoll gradient centrifugation, washed and stained with fluorochrome-conjugated antigen-specific monoclonal antibodies. Cell preparations were acquired and analyzed on a flow cytometer. RESULTS: Centralized FCM was performed for 2 775 patients (82.6%) with B-cell precursor acute lymphoblastic leukemia, 493 patients (14.7%) with T-cell acute lymphoblastic leukemia and 90 patients (2,7%) with biphenotypic acute leukemia. There was a slight overall predominance of male (56.1%) over female (43.9%) patients. Patients with B-cell precursor ALL had a slightly more favourable outcome with a 10 y pEFS of 78 ± 1.0%, compared to patients with a T-ALL or BAL (biphenotypic acute leukemia) phenotype with a 10 y pEFS of 74 ± 1.8% (n.s.) or 69 ± 9.0% (p<0.009), respectively. CONCLUSIONS: FCM according to the EGIL recommendations not only provides diagnostic lineage determination and subclassification but also enables an initial prognostic orientation before MRD (minimal residual disease)-based risk stratification becomes available.

Key treatment questions in childhood acute lymphoblastic leukemia: results in 5 consecutive trials performed by the ALL-BFM study group from 1981 to 2000.

Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients.

Heavy rains control the floating macroplastic inputs into the sea from coastal Mediterranean rivers: A case study on the Têt River (NW Mediterranean Sea).

This study focuses on the relevance of small watersheds in the macroplastic pollution of coastal environments. It aims to identify and quantify in terms of composition, number and mass, current riverine flows of floating macroplastics (>2.5 cm). Estimates are based on 66 visual monitoring of total litter over a 4-year-period (2016-2019) in a small coastal Mediterranean river, the Têt River (NW Mediterranean Sea). The plastic fraction represented 97 % of the observed litter, mainly cigarette butts (20.5 %), polystyrene fragments (18.8 %) and light packaging (16.3 %). The Tet River is characterized by frequent flash-flood events caused by heavy rain, that can induce a sudden rise of the water discharge. Such hydroclimatic forcing greatly influence macroplastic flows, both in terms of their average compositions and loads. We have estimated that 354,000 macroplastic items, corresponding to 0.65 tons, are discharged annually from the Tet River into the sea, and that 73 % of them are released during rain events (∼6 % of the year). The short observation distance from the water surface allowed to exhibit the great abundance of small litter (80 % of them were < 10 cm) and to evaluate to 1.8 g the average mass of floating plastics. Our results suggest that remediation actions must be taken on rainy days and target small litter in order to significantly limit macroplastic inputs from rivers to the sea. Moreover, the large share of cigarette butts in macrolitter inputs demonstrates that reducing ocean pollution cannot be achieved solely by improving waste management, but that changes in social behavior are also needed to stem waste production at the source.

Evidence for tumor cell spread during local hepatic ablation of colorectal liver metastases.

INTRODUCTION: The aim of the present study was to analyze the impact of cryosurgery (CRYO) on liver metastases compared to other thermoablative techniques. In a rat liver metastases model, evidence for tumor cell spread was analyzed comparing CRYO, radiofrequency ablation (RFA), and laser-induced thermotherapy (LITT). METHODS: In an experimental study, we compared cell spillage in the washout of isolated perfused rat livers undergoing thermal ablation. Within the same model, CC531-GFP rat liver tumors were treated with CRYO, RFA, or LITT and the number of vital tumor cells within the perfusate was measured. Matrix metalloproteinases (MMP-2, MMP-9) were analyzed after in vivo ablation of rat colorectal liver metastases in the third experimental model. RESULTS: Our data showed pronounced washout of cells after CRYO with a higher amount of intravascular cells and cell detritus compared to RFA and LITT. Only the effluent fluid of cryosurgery-treated livers revealed GFP-stained tumor cells. MMP-2 and MMP-9 expression was significantly higher after cryosurgery than after RFA and LITT. CONCLUSION: When using thermoablative techniques, intravascular metastatic cell spillage is highest in CRYO, and increased expression of matrix metalloproteinases may further facilitate tumor cell spread. Therefore, RFA and LITT may be preferable whenever surgical resection of liver tumors is impossible.

[Off-label therapy: current problems from the perspective of the Pharmaceutical Commission of the German Medical Profession]. / Off-Label-Therapie: aktuelle Probleme aus Sicht der Arzneimittelkommission der deutschen Ärzteschaft.

The off-label use of approved pharmaceuticals outside the authorized status is implemented in pharmacotherapy of many diseases, especially for rare diseases and in cases of therapy resistance. The German regulations are presented and analyzed and the relative literature is discussed.

Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes.

Site-specific deletions in the tal-1 gene are reported to occur in 12-26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T-ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion regions of the tal-1 deletion breakpoints strongly resemble the RSS and junctional regions of immunoglobulin/T cell receptor (TCR) gene rearrangements, which implies that they are probably caused by the same V(D)J recombinase complex. Analysis of the 134 T-ALL suggested that the occurrence of tal-1 deletions is associated with the CD3 phenotype, because no tal-1 deletions were found in 25 TCR-gamma/delta + T-ALL, whereas 8 of the 69 CD3- T-ALL and 11 of the 40 TCR-alpha/beta + T-ALL contained such a deletion. Careful examination of all TCR genes revealed that tal-1 deletions exclusively occurred in CD3- or CD3+ T-ALL of the alpha/beta lineage with a frequency of 18% in T-ALL with one deleted TCR-delta allele, and a frequency of 34% in T-ALL with TCR-delta gene deletions on both alleles. Therefore, we conclude that alpha/beta lineage commitment of the T-ALL and especially the extent of TCR-delta gene deletions determines the chance of a tal-1 deletion. This suggests that tal-1 deletions are mediated via the same deletion mechanism as TCR-delta gene deletions.

[Hematopoietic growth factors. Possibilities and limitations]. / Hämatopoetische Wachstumsfaktoren. Möglichkeiten und Grenzen.

The production of hematopoietic cells is under the tight control of distinct growth factors. As therapeutic agents, granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoiesis-stimulating agents (TSA) are in routine clinical use. Granulocyte colony-stimulating factor is used to prevent febrile neutropenia or to increase dose-density in chemotherapy regimens. Despite a reduced duration of neutropenia, randomized controlled trials have documented only a modest clinical benefit. A clinical advantage of dose-dense chemotherapy has been shown only in specific chemotherapy regimens. Clinical practice guidelines recommend the use of G-CSF for patients with a high risk of adverse outcome of febrile neutropenia. Erythropoiesis-stimulating agents (ESAs) are used as an alternative to blood transfusion in patients with chemotherapy-induced anemia. However, recent meta-analyses of clinical studies suggest that their use was associated with an increased risk of all-cause mortality and serious adverse events. Thrombopoiesis-stimulating agents have been introduced recently into the market for patients with immune thrombocytopenic purpura. Prior to the use of TSA in other conditions such as chemotherapy-induced thrombocytopenia the lessons learned with G-CSF and ESAs should be taken into account.

A prospective, randomised study on the use of well-fitting masks for prevention of invasive aspergillosis in high-risk patients.

The problem of inhalation of Aspergillus spores outside rooms with high-efficiency particulate air (HEPA) filtration has not been resolved as yet. Well-fitting masks are used in industrial and health care settings to protect from inhaling particles of 0.3-0.5 mum size. To investigate the efficacy and tolerability of well-fitting masks in high-risk patients, we conducted a prospective, randomised, multicentre study comparing standard hospital hygiene procedures with or without wearing masks in adults undergoing chemotherapy for acute leukaemia or allogeneic haematopoietic stem-cell transplantation (aHSCT). Forty-one patients were randomly assigned to wearing masks and 39 to the control group. In all, 76% of patients were treated in laminar airflow or HEPA-filtered rooms, 84% received oral polyenes, and three aHSCT recipients were given fluconazole. Duration of neutropenia was similar in both treatment groups. Invasive fungal infections were diagnosed in eight patients in either study arm. One patient in each arm died from proven invasive aspergillosis. There was no difference in the use of systemic antifungals. Of patients in the mask group, 65% described the comfort as acceptable, 26% as unpleasant, and 9% as intolerable. This first randomised study on the use of well-fitting masks failed to show a reduction of invasive fungal infections.

Gram-positive bacteria: possible photosynthetic ancestry.

A 16S ribosomal RNA gene has been sequenced from Heliobacterium chlorum, the recently discovered photosynthetic bacterium that contains a novel form of chlorophyll. Comparisons with other 16S ribosomal RNA sequences show that the organism belongs to the Gram-positive bacteria (one of ten eubacterial "phyla")--more precisely to the so-called low G + C (G, guanine; C, cytosine) subdivision thereof. This brings to five the number of such phyla that contain photosynthetic species, the other four being the purple bacteria and relatives, the green sulfur bacteria, the green nonsulfur bacteria, and the cyanobacteria. The finding suggests that Gram-positive bacteria may be of photosynthetic ancestry, and it strengthens the case for a common photosynthetic ancestry for all eubacteria.

Gene expression shift towards normal B cells, decreased proliferative capacity and distinct surface receptors characterize leukemic blasts persisting during induction therapy in childhood acute lymphoblastic leukemia.

In childhood acute lymphoblastic leukemia (ALL), persistence of leukemic blasts during therapy is of crucial prognostic significance. In the present study, we address molecular and cell biologic features of blasts persisting after 1 week of induction glucocorticoid therapy. Genome-wide gene expression analysis of leukemic samples from precursor B-cell ALL patients (n=18) identified a set of genes differentially expressed in blasts at diagnosis day 0 (d0) and persisting on day 8 (d8). Expression changes indicate a shift towards mature B cells, inhibition of cell cycling and increased expression of adhesion (CD11b/ITGAM) and cytokine (CD119/IFNGR1) receptors. A direct comparison with normal B cells, which are largely therapy resistant, confirmed the differentiation shift at the mRNA (n=10) and protein (n=109) levels. Flow cytometric analysis in independent cohorts of patients confirmed both a decreased proliferative activity (n=13) and the upregulation of CD11b and CD119 (n=29) in d8 blasts. The differentiation shift and low proliferative activity in d8 blasts may account for the persistence of blasts during therapy and affect their sensitivity to further therapeutic treatment. CD11b and CD119 are potential specific markers for d8 blast persistence and detection of minimal residual disease, which warrant further investigation.

Discriminant function analysis as decision support system for the diagnosis of acute leukemia with a minimal four color screening panel and multiparameter flow cytometry immunophenotyping.

Despite several recommendations for standardization of multiparameter flow cytometry (MFC) the number, specificity and combinations of reagents used by diagnostic laboratories for the diagnosis and classification of acute leukemias (AL) are still very diverse. Furthermore, the current diagnostic interpretation of flow cytometry readouts is influenced arbitrarily by individual experience and knowledge. We determined the potential value of a minimal four-color combination panel of 13 monoclonal antibodies (mAbs) with a CD45/sideward light scatter-gating strategy for a standardized MFC immunophenotyping of the clinically most relevant subgroups of AL. Bone marrow samples from 155 patients with acute myeloid leukemia (AML, n=79), B-cell precursor acute lymphoblastic leukemia (BCP-ALL, n=29), T-cell precursor acute lymphoblastic leukemia (T-ALL, n=12) and normal bone marrow donors (NBMD, n=35) were analyzed. A knowledge-based learning algorithm was generated by comparing the results of the minimal panel with the actual diagnosis, using discriminative function analysis. Correct classification of the test sample according to lineage, that is, BCP-ALL, T-ALL, AML and differentiation of NBMD was achieved in 97.2% of all cases with only six of the originally applied 13 mAbs of the panel. This provides evidence that discriminant function analysis can be utilized as a decision support system for interpretation of flow cytometry readouts.

The effect of prior endoscopic correction of vesicoureteral reflux on open ureteral reimplantation: Surgical outcomes and costs.

INTRODUCTION: Endoscopic injection of a bulking agent is a common first-line approach to the treatment of vesicoureteral reflux (VUR). While early outcomes are comparable to open ureteroneocystotomy, 5-25% of children will eventually develop recurrent reflux necessitating repeat injections or open ureteral reimplantation. OBJECTIVE: To determine whether prior endoscopic injection of a bulking agent impacts outcomes of subsequent open ureteral reimplantation. STUDY DESIGN: Using a retrospective cohort design, radiographic and clinical outcomes of open ureteral reimplantation were compared between patients with and without prior endoscopic correction of reflux. Surgical and hospitalization data were also compared between groups and a cost comparison was performed to assess differences in healthcare costs between the two cohorts. Units of analysis included total ureters or total patients. For certain variables, subanalysis of unilateral versus bilateral reimplantation was included. RESULTS: A total of 258 patients underwent open reimplantation for VUR between 2007 and 2016 by five pediatric urologists. Final analysis (see Summary Table) included 192 patients with pre-operative and postoperative voiding cystourethrogram (VCUG) and follow-up data at a median 4.95 months. Among 317 reimplanted refluxing ureters, radiographic resolution was reached in 26/27 (96.3%) patients with and 279/290 (96.2%) without prior endoscopic treatment (P = 0.981). Clinical success was achieved in 17/17 (100%) patients with and 174/175 (99.4%) without prior endoscopic treatment (P = 0.755). There were no statistically significant differences between duration of surgery or length of hospital stay. There were no statistically significant differences between total charges, total costs, and operating room (OR) costs between groups. DISCUSSION: This study indicated that prior endoscopic injection of a bulking agent did not impact the outcomes or costs of subsequent open ureteroneocystotomy. While prior studies have demonstrated tissue changes associated with injection of a bulking agent, these did not seem to significantly impact the difficulty of later open surgery or the success rates compared to patients who proceeded directly to open correction of reflux. CONCLUSION: Open ureteral reimplantation for recurrent VUR after failed endoscopic injection of a bulking agent was safe and effective, with comparable outcomes and costs to open surgery in patients without prior endoscopic correction.

Loss of heterozygosity on chromosome 6q14-q24 is associated with poor outcome in children and adolescents with T-cell lymphoblastic lymphoma.

Deletions of chromosome 6q have been reported in several hematological malignancies, but data are not conclusive regarding their biological and prognostic impact. Therefore, we focused on pediatric patients diagnosed with T-cell lymphoblastic lymphoma (T-LBL) treated uniformly according to the NHL-BFM95 protocol. We used loss-of-heterozygosity (LOH) analysis of 25 microsatellite markers located on chromosome 6q14-q24. Fragment-length analysis was performed on ABI-PRISM3100 Genetic-Analyzer. Eligibility criterion was > or =3 informative markers. Between April 1995 and March 2003, 185 T-LBL patients were treated according to the NHL-BFM95 protocol. Five-year event-free (EFS) and disease-free survival (DFS) were 79+/-3 and 87+/-3% (median follow-up 4.7 [1.2-10.1] years). Sixty-one patients were evaluable for LOH analysis, including 18 out of 23 patients with relapse. EFS and DFS were 67+/-6 and 69+/-6% for these 61 patients. Testing of 853 markers in the 61 patients identified the presence of LOH in 19 patients (31%): 13 of the 18 relapse patients and five of the 41 in complete remission (odds ratio 18.7, 95% confidence interval 4.7-75.3). One LOH-positive patient died from treatment-related toxicity. We conclude that LOH on chromosome 6q14-q24 may have conferred a high risk of relapse on our group of children with T-LBL treated according to the NHL-BFM95 protocol.