SC is a frequent and usually progressive sequela of multisystem LCH in our institution. LTx has become the treatment of choice for the majority of patients and should be considered early in cases with severe hepatic involvement.

According to our data, pulmonary compromise without other risk organ involvement does not appear to be a negative prognostic factor in our study.

The aim of this study was to retrospectively evaluate clinical characteristics at diagnosis and outcome of patients with Langerhans cell histiocytosis (LCH). From October 1987 to March 1996, 133 patients with confirmed LCH were admitted to Hospital JP Garrahan in Buenos Aires (123 evaluable). Median age was 5 years (range 15 days to 18 years). Initial organ involvement included bone 114 patients, ear 34, skin 30, liver 18, lung 14, lymph nodes 14, spleen 12, diabetes insipidus 9, and bone marrow 2. Nineteen patients had organ dysfunction, pulmonary 14, hematological 14, and hepatic 12. Two groups were defined: Group A included patients with single system disease (uni- or multifocal) and group B multisystem (with or without organ dysfunction). In group A (n = 82), 24 patients were treated with chemotherapy (prednisone and vinblastine), 21 with surgery, 15 received radiotherapy, and 22 were only observed. Patients of group B (n = 41) were treated with chemotherapy consisting of prednisone and vinblastine, DALHX 83, or LCH1-based chemotherapy. At a median follow-up of 3 years (range 1 month-8 5/12 years) 93% of patients of group A and 39% of group B survive free of reactivation. In group B, 22% had a reactivation and 39% died of progressive disease. Sequelae were detected in 35 patients (28%), which included diabetes insipidus in 17, hearing loss in 13, bony sequelae in 11, sclerosing cholangitis in 6, and lung fibrosis with bullae in 6. Two patients had a subsequent malignant disease. A total of 17 (14%) patients died and 16 of them belonged to the group B: 13 died of progressive disease, 2 due to sclerosing cholangitis (with sepsis in one case and encephalitis in the other one), 1 with progressive disease and associated myelofibrosis, and 1 patient of group A with active disease and brain stem tumor. Patients who had organ dysfunction had a reactivation free survival of 32%. All these patients survived with sequelae. Logistic regression analysis showed that organ dysfunction and hematological involvement had significant predictive values in relation to death. Patients of group A had an excellent survival rate, whereas in those of group B a high mortality was found, especially in the subgroup of patients with organ dysfunction. Lahey's criteria should be revised. Sequelae were also more common in this group.

BACKGROUNDRecent reports and previous randomized trials conducted at the authors' institution suggested that children with lower risk febrile neutropenic (LRFN) may benefit from substitution of oral antibiotic therapy for parenteral therapy. The objective of this study was to determine the efficacy of parenteral‐oral outpatient therapy in the management of children with LRFN who were receiving treatment for malignant disease.METHODSFrom August 2000 to April 2002, 135 children with a median age of 7.5 years (range, 1.6–15.8 years) who had a total of 177 episodes of LRFN were included in a prospective, randomized, single‐institution trial. Children with LRFN received a single dose of ceftriaxone and amikacin and completed a risk‐assessment work‐up. All patients were discharged immediately and, at 24 hours, were allocated randomly to two groups: Group A (89 episodes) received oral ciprofloxacin, and Group B (88 episodes) received intravenous ceftriaxone.RESULTSMost patients (61% in Group A and 51% in Group B) were receiving treatment for leukemia (P value not significant [NS]). Twenty‐eight children (31%) in Group A and 22 children (25%) in Group B displayed unexplained fever (P value NS). No significant differences in sites of initial infection were found between the two groups. The median duration of neutropenia was 4.2 days and 4.7 days for Group A and Group B, respectively (P value NS); the median duration of fever was 2.3 days and 2.6 days, respectively (P value NS); and the median duration of antibiotic treatment was 4.5 days and 4.8 days, respectively (P value NS). The overall results of the study were excellent. Only four treatment failures in Group A (5%) and 6 treatment failures in Group B (7%) were observed. These patients were readmitted to the hospital and did well with appropriate treatment.CONCLUSIONSIn children with LRFN who are receiving treatment for malignant disease, outpatient oral ciprofloxacin after 24 hours of a single dose of intravenous ceftriaxone and amikacin was as safe and efficacious as parenteral ceftriaxone. Outpatient management and early antibiotic withdrawal were safe for both groups. Cancer 2003;97:1775–80. © 2003 American Cancer Society.DOI 10.1002/cncr.11251

BACKGROUND Recent reports and a previous randomized trial conducted at the authors' institution suggested that a lower risk subset of children with febrile neutropenia under chemotherapy might benefit of an oral antibiotic outpatient approach. METHODS The objective of this study was to test the efficacy of oral ciprofloxacin in the treatment of lower risk febrile neutropenia (LRFN) in children treated for malignant diseases. From November 1998 to December 1999, 93 episodes of LRFN in 87 children (median age, 5.5 years; range, 0.9–15.8 years) were included in a prospective randomized controlled single institution trial. Inclusion criteria included fever (> 38 °C), severe neutropenia (absolute neutrophil count, < 500/mm3), and lower risk features (e.g., absence of severe comorbidity factors, good clinical condition, negative blood cultures, control of local infection, prediction of a period of neutropenia less than 10 days after admission, and compliant parents). After 24 hours of a single intravenous ceftriaxone (100 mg/kg) plus amikacin (15 mg/kg) and completed risk assessment workup, patients were discharged and randomly allocated to two groups. Group A (48 episodes) received ciprofloxacin 20 mg/kg/day orally (p.o.) every 12 hours for 6 days. Group B (45 episodes) received intravenous ceftriaxone plus amikacin for 2 days more followed by cefixime (8 mg/kg/day p.o.) every 24 hours for 4 additional days. Failure was defined as the need of a second hospitalization during the same episode. RESULTS Most of the patients (59% in Group A and 52% in Group B) were treated for malignant solid tumors. Fifteen (31%) children in Group A and 15 (33%) in Group B presented with fever of unknown origin (P value was not significant). No significant differences were found in sites of initial infection between both groups. Overall results in this study were excellent. Only one patient with respiratory failure was detected in Group B, who did well with secondary treatment. CONCLUSIONS In febrile neutropenic children after anticancer therapy and lower risk features, oral ciprofloxacin for 6 days after 24 hours of intravenous ceftraxione plus amikacin appears to be as efficacious as intravenous ceftriaxone plus amikacin for 2 days more followed by cefixime for 4 additional days. These results contribute to strengthen the concept of LRFN. Cancer 2001;91:1563–7. © 2001 American Cancer Society.

Incidence of reactivation correlates with the stage of the disease at diagnosis. Incidence of sequelae correlates with the occurrence of reactivations.

We describe the outcome of a 20-month-old female and a 6-year-old male, both of whom had acutely developed severe respiratory distress with tachypnea, cyanosis and, in Patient 2, thoracic pain. Chest X-ray and CT scan showed interstitial pulmonary involvement and a bullous process with bilateral pneumothoraces for both children. Pulmonary biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH). Laboratory testing and skeletal radiography did not reveal any other involvement of LCH. The patients received chemotherapy (prednisone, vinblastine, 6-mercaptopurine). They had recurrent episodes of pneumothorax during follow-up and placement of chest tubes was the treatment chosen. They were asymptomatic, with regression of bullae and disappearance of pneumothorax at 58 and 63 months of follow-up, respectively. Pulmonary function tests done during follow-up were normal in both patients. Despite severe pulmonary involvement, conservative surgical treatment and moderate chemotherapy produced good results in these two rare cases.

were re-imaged within the recommended time period had a shorter duration of oral antifungal therapy, emphasizing the importance of minimizing delayed imaging. Further collaborative studies would help to characterize stopping criteria in larger cohorts of patients. AcknowledgementsThis work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding Scheme. Author contributionsAll authors were involved in the design of the research. MAVM and KSP performed the research, analysed the data and wrote the manuscript. KJT and KSP revised the manuscript. Competing interestsMAVM has received an independent speaker honorarium from Pfizer. KSP has received research funding from Merck, and advisory board honoraria from Pfizer, Merck and Gilead. Reduced doses of cladribine and cytarabine regimen was effective and well tolerated in patients with refractory-risk multisystem Langerhans cell histiocytosisLangerhans cell histiocytosis (LCH) is a rare disease in which lesions contain cells with features similar to the Langerhans cell of the epidermis. The clinical forms of LCH range from a self-healing unique lesion to multisystem (MS) involvement with risk organ (RO) dysfunction resistant to current therapies. Very young children with MS disease and hepatic or haematological dysfunction are usually treated with multiagent chemotherapy including vinblastine and corticosteroids, but the prognosis of patients with disease progression during this 'standard' chemotherapy is extremely poor (Gadner et al, 2001). Our previous study analysed the poor prognosis of this high-risk group of patients, who presented an overall 3-year survival rate less than 20% (Braier et al, 2010).