| Autor(en) |
Titel |
Quelle |
Links |
| The French Langerhans' Cell Histiocytosis Study Group |
A multicentre retrospective survey of Langerhans' cell histiocytosis: 348 cases observed between 1983 and 1993. |
Archives of disease in childhood 1996, 75: 17 |
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| In a retrospective study involving 32 haematology/oncology departments in France, 348 cases of Langerhans' cell histiocytosis diagnosed between 1983 and 1993 were collated. The percentage of males was 56.4%. Median age at diagnosis was 30.2 months. The median follow up was 35.5 months. Initially, 108 patients (31%) had isolated unifocal or bifocal bone involvement, 67 (19%) had isolated multifocal bone involvement, 136 (39%) had soft tissue involvement without organ dysfunction, and 37 (11%) had organ dysfunction. Two thirds of the sites of involvement diagnosed throughout the course of the disease were present at diagnosis, while the remaining one third appeared during a relapse. Treatment was tailored to the individual patient and was extremely varied, hampering any comparison of regimens. Vinblastine with or without steroids was the most common regimen when systemic chemotherapy was used for the first episode (246/348). Twenty four of the 216 patients received VP 16 as first line treatment. Two patients with progressive multiorgan relapse, despite the use of several drugs, underwent bone marrow transplantation and are alive and disease free 60 and 22 months later. Altogether 21.9% of patients had sequelae, including diabetes insipidus in 17.5% of cases. The overall survival rate is 91.7% (confidence interval 90.7 to 95%) three years after diagnosis. In the univariate analysis, age less than 1 year, ear, nose, and throat, cutaneous, lymph node, liver, spleen, lung, marrow and intestinal involvement, male sex, progressive episodes, the absence of response, and partial responses, were associated with a poor vital prognosis. In a multivariate analysis of prognostic factors, poor early outcome emerged as the most important parameter, closely linked to other poor outcome features such as young age and organ dysfunction. It identified a small number of patients with a poor initial response to treatment, for whom intensive treatment should be assessed in a phase II trial. |
| Growth Hormone Research Society |
Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. |
J clin endocrinol Metab. 85:3990-3 |
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| Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S, Histiocyte Society |
A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. |
The Journal of pediatrics 2001, 138: 728 |
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| To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. |
| Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S, Histiocyte Society |
Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. |
Blood 2008 Mar 1; 111: 2556 |
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| Multisystem Langerhans cell histiocytosis (MS-LCH) is associated with high mortality when patients have risk organ involvement (RO(+)) or are younger than 2 years. In an international randomized trial, LCH-II, we intensified their treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine followed by 18 weeks of daily 6-mercaptopurine with vinblastine/prednisone pulses; etoposide was added in arm B. Considering all 193 randomized risk patients, there were similar outcomes: rapid (6 weeks) response (arm A vs arm B: 63%/71%), 5-year survival probability (74%/79%), disease reactivation frequency (46%/46%), and permanent consequences (43%/37%). However, (1) patients younger than 2 years without RO involvement (RO(-)) had 100% survival and uniformly high (> 80%) rapid response, (2) RO(+) patients not responding within 6 weeks had highest mortality, and (3) importantly, the more intensive arm B reduced mortality in RO(+) patients (relative hazard rate, accounting for differences in risk organ involvement, of 0.54; 95% CI = 0.29-1.00). Finally, comparison of RO(+) patients in LCH-I and LCH-II confirmed that increasing treatment intensity increased rapid responses (from 43% in arm A LCH-I to 68% in arm B LCH-II; P = .027) and reduced mortality (from 44% in arm A LCH-I to 27% in arm B LCH-II; P = .042). We conclude that intensified treatment significantly increases rapid response and reduces mortality in risk MS-LCH. This trial was registered at http://www.controlled-trials.com as no. ISRCTN57679341. |
| Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S, Histiocyte Society |
Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. |
Blood 2013 Jun 20; 121: 5006 |
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| Langerhans cell histiocytosis (LCH)-III tested risk-adjusted, intensified, longer treatment of multisystem LCH (MS-LCH), for which optimal therapy has been elusive. Stratified by risk organ involvement (high [RO+] or low [RO-] risk groups), > 400 patients were randomized. RO+ patients received 1 to 2 six-week courses of vinblastine+prednisone (Arm A) or vinblastine + prednisone + methotrexate (Arm B). Response triggered milder continuation therapy with the same combinations, plus 6-mercaptopurine, for 12 months total treatment. 6/12-week response rates (mean, 71%) and 5-year survival (84%) and reactivation rates (27%) were similar in both arms. Notably, historical comparisons revealed survival superior to that of identically stratified RO+ patients treated for 6 months in predecessor trials LCH-I (62%) or LCH-II (69%, P < .001), and lower 5-year reactivation rates than in LCH-I (55%) or LCH-II (44%, P < .001). RO- patients received vinblastine+prednisone throughout. Response by 6 weeks triggered randomization to 6 or 12 months total treatment. Significantly lower 5-year reactivation rates characterized the 12-month Arm D (37%) compared with 6-month Arm C (54%, P = .03) or to 6-month schedules in LCH-I (52%) and LCH-II (48%, P < .001). Thus, prolonging treatment decreased RO- patient reactivations in LCH-III, and although methotrexate added no benefit, RO+ patient survival and reactivation rates have substantially improved in the 3 sequential trials. (Trial No. NCT00276757 www.ClinicalTrials.gov). |
| Galluzzo ML, Braier J, Rosenzweig SD, Garcia de Dávila MT, Rosso D |
Bone marrow findings at diagnosis in patients with multisystem langerhans cell histiocytosis. |
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2010 Mar-Apr; 13: 101 |
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| This study was designed to describe the bone marrow features of multisystem Langerhans cell histiocytosis (LCH) at diagnosis in patients with or without hematologic dysfunction. A retrospective review of bone marrow biopsies from patients with multisystem LCH was performed. Cases were diagnosed at the Garrahan Hospital between 1987 and 2004. Routine and immunohistochemistry techniques (hematoxylin-eosin, periodic acid-Schiff, Giemsa, Gomori reticulin, and CD1a, CD68, and CD61) were evaluated. Clinical outcome and laboratory data were obtained from the medical charts. Twenty-two bone marrow biopsies from patients with multisystem LCH were reviewed at onset of disease. Four patients had no hematologic dysfunction and the other 18 patients had monocytopenia (9), bicytopenia (7), or tricytopenia (2). Increased number and dysplasia of megakaryocytes were evident in 22/22 samples and emperipolesis was present in 21/22 (95%). Aggregates of histiocytes and hemophagocytosis were seen in 9/22 samples. Myelofibrosis was found in 16/17 (94%) evaluable samples at diagnosis. No association of myelofibrosis and cytopenias or clinical outcome was found. Positive CD1a confirmed the presence of LCH cells in 3/22 (14%) samples. Hemophagocytosis and poor outcome were significantly more common in patients with bilineage and trilineage cytopenias. Langerhans cell histiocytosis cells were rarely seen in the bone marrow of these patients (14%); increased histiocytes and hemophagocytosis were more commonly found (41%). Hemophagocytosis was associated with severe cytopenias. Bicytopenia and tricytopenia were associated with poor outcome (death). Myelofibrosis, megakaryocytic dysplasia, and emperipolesis were common findings. |
| Gaundong Mbéthé GL, Dejean C, Henriques de Figueiredo B, Sargos P, Italiano A, Kantor G |
[Multifocal Langerhans cell histiocytosis of bone: indications for radiotherapy]. |
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique 2010, 14: 759 |
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| Langerhans cell histiocytosis is a non-malignant proliferative disease of unknown etiology that can affect one or more organs. This is a rare disease, 1 to 2/100,000, affecting mainly children with a male predominance. The osseous lesions are the most frequent (60 to 90%). There is however no consensus treatment for the management of these sites. We report the cases of two patients successfully treated with radiotherapy after primary chemotherapy, at doses of 15 Gy in ten sessions of 1.5 Gy for one patient and 18 Gy in ten fractions of 1.8 Gy for the other. Single or multifocal bone Langerhans cell histiocytosis without visceral involvement is a benign, self-limiting affection in most cases. Some bone lesions could be treated by radiotherapy alone. But the high variability of doses currently given in the literature does not allow determining the lowest effective dose limiting the risk of secondary neoplasia or impaired growth in children, in whom lower doses of 6 to 8 Gy are recommended. The decision of radiotherapy must be weighed against the risk of the disease. Caution should be the rule in this non-malignant tumour pathology. |
| Girschikofsky M, Arico M, Castillo D, Chu A, Doberauer C, Fichter J, Haroche J, Kaltsas GA, Makras P, Marzano AV, de Menthon M, Micke O, Passoni E, Seegenschmiedt HM, Tazi A, McClain KL |
Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. |
Orphanet journal of rare diseases 2013 May 14; 8: 72 |
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| Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body. Most of the knowledge about the diagnosis and therapy is based on pedriatic studies. Adult LCH patients are often evaluated by physicians who focus on only the most obviously affected organ without sufficient evaluation of other systems, resulting in patients being underdiagnosed and/or incompletely staged. Furthermore they may be treated with pediatric-based therapies which are less effective and sometimes more toxic for adults. The published literature on adult LCH cases lacks a comprehensive discussion on the differences between pediatric and adult patients and there are no recommendations for evaluation and comparative therapies. In order to fill this void, a number of experts in this field cooperated to develop the first recommendations for management of adult patients with LCH. Key questions were selected according to the clinical relevance focusing on diagnostic work up, therapy, and follow up. Based on the available literature up to December 2012, recommendations were established, drafts were commented by the entire group, and redrafted by the executive editor. The quality of evidence of the recommendations is predominantly attributed to the level of expert opinion. Final agreement was by consensus. |
| Greenberger JS, Cassady JR, Jaffe N, Vawter G, Crocker AC |
Radiation therapy in patients with histiocytosis: management of diabetes insipidus and bone lesions. |
International journal of radiation oncology, biology, physics 1979, 5: 1749 |
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| Grois N, Prayer D, Prosch H, Lassmann H, CNS LCH Co-operative Group |
Neuropathology of CNS disease in Langerhans cell histiocytosis. |
Brain : a journal of neurology 2005, 128(Pt 4): 829 |
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| CNS involvement in Langerhans cell histiocytosis (LCH) is a rare but potentially devastating disorder. Different types of involvement have been described by MRI. CNS changes can have space-occupying or degenerative character. Little is known about the underlying neuropathology and pathophysiology. In our study we reviewed brain samples from 12 patients with LCH. The neuropathology findings were correlated with the MR morphology and the clinical presentation. By neuropathology, three types of lesions were distinguished. (i) Circumscribed granulomas within the brain's connective tissue space corresponded to tumorous lesions in the meninges or choroid plexus on MRI. They showed a composition similar to Langerhans granulomas in peripheral organs, with variable presence of CD1a-reactive cells and pronounced CD8-positive (+) T-cell infiltration. (ii) Granulomas occur within the brain's connective tissue spaces with partial infiltration of the surrounding CNS parenchyma by CD1a-reactive histiocytes. This was associated with profound T-cell-dominated inflammation and severe neurodegeneration, characterized by a nearly complete loss of neurons and axons, and gliosis. (iii) Neurodegenerative lesions lacking infiltration of CD1a+ cells, mainly affecting the cerebellum and brainstem, exhibited a profound inflammatory process dominated by CD8-reactive lymphocytes, associated with tissue degeneration, microglial activation and gliosis. Patients with such lesions showed different stages of neurological deterioration. This study indicates that neurodegeneration in LCH occurs on the background of a T-cell-dominated inflammatory process and is characterized by neuronal and axonal destruction with secondary demyelination, resembling paraneoplastic encephalitis. |
| Grois N, Pötschger U, Prosch H, Minkov M, Arico M, Braier J, Henter JI, Janka-Schaub G, Ladisch S, Ritter J, Steiner M, Unger E, Gadner H, DALHX- and LCH I and II Study Committee |
Risk factors for diabetes insipidus in langerhans cell histiocytosis. |
Pediatric blood & cancer 2006, 46: 228 |
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| Diabetes insipidus (DI) is the most frequent central nervous system (CNS)-related permanent consequence in Langerhans cell histiocytosis (LCH), which mostly requires life-long hormone replacement therapy. In an attempt to define the population at risk for DI, 1,741 patients with LCH registered on the trials DALHX 83 and DALHX 90, LCH I and LCH II were studied. |
| Grois N, Fahrner B, Arceci RJ, Henter JI, McClain K, Lassmann H, Nanduri V, Prosch H, Prayer D, Histiocyte Society CNS LCH Study Group |
Central nervous system disease in Langerhans cell histiocytosis. |
The Journal of pediatrics 2010, 156: 873-81, 881.e1 |
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