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Objective:To understand the clinical characteristics and prognosis of Langerhans cell histiocytosis (LCH) with skin-limited lesion.Methods:A retrospective analysis was performed on clinical characteristics and prognosis of 16 skin-limited LCH patients, out of 578 LCH patients who were hospitalized in Beijing Children′s Hospital during December 2013 to June 2018.Results:A total of 16 skin-limited LCH cases, accounted for 2.7% of all 578 cases, were included.Among which, sex ratio (male vs.female) was 1.28∶1.00.Median ages of skin eruption occurrence and of diagnosis of the disease were 3.5 months (3 days to 2 years and 5 months) and 6 months (2 months 14 days to 2 years and 8 months) in this group.Among the 16 cases, seborrheic dermatitis-like lesions(11 cases, 68.7%) was the most common, and the trunk was most frequently involved[75.0% (12 cases)]. Serine/threonine protein kinase gene V600E [ BRAF (p.V600E)] mutation was detected in pathological specimens from 10 skin-limi-ted cases, with 9 cases being positive.Plasma samples from 5 positive cases were further detected for BRAF (p.V600E) mutation, and 4 positive results were gained.Of all 16 patients, 11 cases (68.7%) were treated.Remission were achieved in 3-6 months from treatment start in patients treated whether according to the Histiocyte Society′s LCH-2009 protocol for 25 weeks(6 cases, 37.5%), or with topical mometasonefuroate for 3 months (3 cases, 18.8%). Two patients(12.5%) with solitary cutaneous lesions underwent excision biopsy (one face and one prepuce) and were considered to be in remission immediately after surgery.None of these patients suffered from the recurrence of the disease.The remaining 5 patients (31.3%) with skin-limited LCH were just evaluated regularly, and achieved remission in 3-6 months of commencing observation.Among these untreated patients, 1 with consistently positive BRAF (p.V600E) mutation in plasma had bone involvement in the 24 th month of assessment, and was then treated based on the Histiocyte Society′s LCH-2009 Protocol.No clinical or imageological evidence supporting disease progression was found on this patient.Median follow-up period was 32.8 months (2.9-63.9 months). Except one patient, none of the rest cases had active disease till follow-up ended.Two-year event free survival(EFS) of this research was (92.3± 7.4)%.There was no significant difference between EFS of treated group and that of observation group( χ2=1.250, P=0.264). Conclusions:Skin-limited LCH often occurs in infants and newborns, with strong heterogeneity in clinical manifestations, laboratory indicators, and pathogenesis.Seborrheic dermatitis-like lesions were the most common cutaneous type.The prognosis of the patients is excellent despite progressing into multisystem involvement can be seen in a few patients.
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Objective To investigate the clinical characteristics and outcomes of pediatric Langerhans cell histiocytosis (LCH) with craniofacial bone involvement.Methods A retrospective analysis was performed on 145 pediatric LCH patients with craniofacial bone involvement registered at Beijing Children's Hospital Affiliated to Capital Medical University from January 2007 to July 2013.The patients were divided into 2 groups:central nervous system risk craniofacial bone involvement group(CNS-RISK) and non-central nervous system risk craniofacial bone involvement group(non-CNS-RISK).All patients were assessed at 5 weeks,11 weeks,25 weeks and 52 weeks respectively after chemotherapy started,and 3 months,6 months,1 year and 3 years after chemotherapy withdrawal.Statistics and related risk analysis was performed respectively.Results A total of 145 craniofacial bone involved LCH cases were included,which was composed of 62.5％ of 232 LCH cases hospitalized during the same period.The median age of these patients was 29 months,and median follow-up time period was 31 months.The most commonly involved craniofacial bone was parietal bone(78 cases,53.8％),followed by temporal bone(59 cases,40.7％) and frontal bone(57 cases,39.3％).The onset age was significantly different (26 months vs.54 months,Z =-2.777,P ＜ 0.05) between CNS-RISK group (103 cases) and non-CNS-RISK group (42 cases).Moreover,compared with non-CNS-RISK group,CNS-RISK group showed higher ratio of patients classified as multisystem involvement of risk organs (72/103 cases,69.9％) vs.(15/42 cases,35.7％) (x2 =16.908,P ＜ 0.05),and a higher rate of overall relapse rate (45/103 cases,43.7％) vs.(7/42 cases,16.7％) (x2 =9.427,P ＜ 0.05),a lower survival rate of 3-year relapse-free survival rate [(66.9 ± 5.7) ％ vs.(88.2 ± 7.8) ％,Z =2.205,P ＜ 0.05].The incidence of diabetes insipidus was 13.7％ in 232 LCH patients.Compared with patients without craniofacial bone involvement,patients with craniofacial bone involvement demonstrated a higher rate of diabetes insipidus [(27/145 cases,18.6％) vs.(5/87 cases,5.7％),x2 =7.579,P =0.006].But the incidence of diabetes insipidus showed no statistical difference between CNS-RISK group and non-CNS-RISK group (21.3 ％ and 11.9 ％,x2 =1.760,P =0.185).Diabetes insipidus was not found in single system LCH with Single-Bone CNS-RISK lesions.Till the end of follow-up,1 out of 145 patients died.Among 145 patients,5 cases had a single-bone CNS-RISK lesion.They received systemic chemotherapy.One showed reactivation,and none of them died.Multivariate analysis of variance showed that all the independent factors indicating diabetes insipidus included parietal bone,frontal bone,maxilla and mandible involvement (HR =2.697,3.487,5.425,all P ＜ 0.05),while independent factors indicating relapse included temporal bone,maxilla and mandible involvement (HR =3.712,3.380,all P ＜ 0.05).Conclusions Among involved craniofacial bones,the parietal bone is most commonly involved.LCH occurs averagely at an earlier age in CNS-RISK group,along with lower 3-year relapse-free survival rate,high relapse rate,and more patients classified as multisystem LCH involvement of risk organs.The incidence of diabetes insipidus in children with craniofacial bone involvement with single system CNS-RISK is low.Patients with the parietal bone,frontal bone,maxilla and mandible involvement at diagnosis are at a increasing risk a significantly to develop DI during the course of disease.
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Objective@#To investigate the clinical characteristics and outcomes of pediatric Langerhans cell histiocytosis (LCH) with craniofacial bone involvement.@*Methods@#A retrospective analysis was performed on 145 pediatric LCH patients with craniofacial bone involvement registered at Beijing Children′s Hospital Affiliated to Capital Medical University from January 2007 to July 2013.The patients were divided into 2 groups: central nervous system risk craniofacial bone involvement group(CNS-RISK) and non-central nervous system risk craniofacial bone involvement group(non-CNS-RISK). All patients were assessed at 5 weeks, 11 weeks, 25 weeks and 52 weeks respectively after chemotherapy started, and 3 months, 6 months, 1 year and 3 years after chemotherapy withdrawal.Statistics and related risk analysis was performed respectively.@*Results@#A total of 145 craniofacial bone involved LCH cases were included, which was composed of 62.5% of 232 LCH cases hospitalized during the same period.The median age of these patients was 29 months, and median follow-up time period was 31 months.The most commonly involved craniofacial bone was parietal bone(78 cases, 53.8%), followed by temporal bone(59 cases, 40.7%) and frontal bone(57 cases, 39.3%). The onset age was significantly different (26 months vs.54 months, Z=-2.777, P<0.05) between CNS-RISK group (103 cases) and non-CNS-RISK group (42 cases). Moreover, compared with non-CNS-RISK group, CNS-RISK group showed higher ratio of patients classified as multisystem involvement of risk organs (72/103 cases, 69.9%)vs.(15/42 cases, 35.7%)(χ2=16.908, P<0.05), and a higher rate of overall relapse rate (45/103 cases, 43.7%) vs. (7/42 cases, 16.7%) (χ2=9.427, P<0.05), a lower survival rate of 3-year relapse-free survival rate [(66.9±5.7)% vs.(88.2±7.8)%, Z=2.205, P<0.05]. The incidence of diabetes insipidus was 13.7% in 232 LCH patients.Compared with patients without craniofacial bone involvement, patients with craniofacial bone involvement demonstrated a higher rate of diabetes insipidus [(27/145 cases, 18.6%) vs.(5/87 cases, 5.7%), χ2=7.579, P=0.006]. But the incidence of diabetes insipidus showed no statistical difference between CNS-RISK group and non-CNS-RISK group (21.3% and 11.9%, χ2=1.760, P=0.185). Diabetes insipidus was not found in single system LCH with Single-Bone CNS-RISK lesions.Till the end of follow-up, 1 out of 145 patients died.Among 145 patients, 5 cases had a single-bone CNS-RISK lesion.They received systemic chemotherapy.One showed reactivation, and none of them died.Multivariate analysis of variance showed that all the independent factors indicating diabetes insipidus included parietal bone, frontal bone, maxilla and mandible involvement(HR=2.697, 3.487, 5.425, all P<0.05), while independent factors indicating relapse included temporal bone, maxilla and mandible involvement(HR=3.712, 3.380, all P<0.05).@*Conclusions@#Among involved craniofacial bones, the parietal bone is most commonly involved.LCH occurs averagely at an earlier age in CNS-RISK group, along with lower 3-year relapse-free survival rate, high relapse rate, and more patients classified as multisystem LCH involvement of risk organs.The incidence of diabetes insipidus in children with craniofacial bone involvement with single system CNS-RISK is low.Patients with the parietal bone, frontal bone, maxilla and mandible involvement at diagnosis are at a increasing risk a significantly to develop DI during the course of disease.
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Objective To investigate the clinical characteristics,treatment,and prognostic factors for Langerhans cell histiocytosis (LCH) in children.Methods A retrospective review of patients diagnosed as LCH was carried out between January 2007 and December 2012 in Beijing Children's Hospital,Capital Medical University.Target patients were divided into multi-organ high-risk groups (Group Ⅰ),multi-organ low-risk groups (Group Ⅱ),single-organ groups (GroupⅢ),and the corresponding intensity of chemotherapy was given.SPSS 17.0 statistical software was used to analyze the findings.The correlations among the affected organ,the early treatment response and the prognosis were analyzed.Results A total of 217 patients were analyzed including 127 boys and 90 girls with ratio of 1.4 ∶ 1.0 and a median age of 36 months (ranged from 2 months to 14 years) on the diagnosis of LCH,and there were 132 cases (60.8％) in group Ⅰ,33 cases (15.3％) in group Ⅱ and 52 cases (23.9％) in group Ⅲ.The median age on diagnosis was 20 months in group Ⅰ,42 months in group Ⅱ and 72 months in group Ⅲ.The most frequently affected organ was the bone (176 cases,81.2％).Among 217 patients,55 cases (25.3％) had recurrence and 12 cases died.The rate of 3-year overall survival was expected to be 90.78％.The rate of 3-year event free survival was expected to be 76.5％.Myelosuppression,liver function damage and infection were the most common side effects due to chemotherapy with the percentages of 48.4％ (105 cases),24.0％ (52 cases) and 12.4％ (27 cases).Risk organs involvement and no-response to initial therapy (after 6 weeks) indicated a worse prognosis (x2 =10.60,12.84,P =0.017,0.001).Conclusions Incidence of LCH in boys is slightly higher than girls in children.Peak age at onset of LCH in children is 1-3 years old.Bone is the most frequent involved organ.Involvement of risk organs and no-response to initial therapy are key factors in determining worse prognosis.A rescue therapy should be introduced earlier in these patients.
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Objective To explore the clinical features of Langerhans cell histiocytosis (LCH) involving the thyroid gland in children,in order to improve the diagnosis and treatment.Methods The clinical and imaging manifestations,thyroid function,treatment and prognosis of hospitalized children with LCH involving the thyroid gland in Beijing Children's Hospital,Capital Medical University,from July 2007 to July 2016 were analyzed retrospectively.Results In total 556 cases with LCH were analyzed,among which 8 cases (1.44％) were with LCH involving the thyroid gland.The onset age of children with LCH involving the thyroid gland was significantly older than the others with significant difference (average onset age:7.6 vs.3.4 year old;t =2.748,P =0.006),while the sex distribution showed no significant difference (1.67 ∶ 1.00 vs.1.38 ∶ 1.00;x2 =0.064,P =0.799).All 8 cases were Group Ⅰ,complicated by multiple organ involvement with vital organs included.None of the 8 cases had significant clinical symptoms of hypothyroidism,and thyroid imaging abnormalities were found in all 8 cases,including goiters and low echoes with irregular shapes,while 5 cases had subclinical hypothyroidism.All 8 cases were given the first-line standard chemotherapy for LCH-Group Ⅰ.Three cases without subclinical hypothyroidism showed good treatment effects and were assessed as non-active state and had already quitted medication.Five cases complicated by subclinical hypothyroidism had unsatisfactory treatment effects,among which 1 case abandoned treatment and 4 cases were adjusted for the second-line standard chemotherapy (Prednisone + Vincristine + Cytarabine + Cladribine).Finally,1 out of 4 case was assessed as non-active state after 3 months of medicine withdrawal,the other 3 cases were still in maintenance therapy.Conclusions LCH involving the thyroid gland is extremely rare,with significantly older onset age,and easily complicated by multiple organ involvement with vital organs included.Patients have no significant clinical symptoms of hypothyroidism,while some have subclinical hypothyroidism.The major imaging changes are goiters and low echoes with irregular shapes.Those LCH involving the thyroid gland complicated by subclinical hypothyroidism turn out to have poor prognosis,but Cladribine and Cytarabine are possible to improve the prognosis of such patients.
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Objective To analyze the clinical characteristics of juvenile myelomonocytic leukemia(JMML) and the PCNA levels of the hyperoxia -exposure group (6 h)decreased,and the difference in PCNA protein expres-sion levels was significant of gene diagnose for JMML.Methods Clinical data were retrospectively analyzed in 21 pa-tients suffering from JMML based on new 2009 World Health Organization diagnostic criteria from January 201 3 to June 201 4 in Beijing Children′s Hospital,Capital Medical University.Results There were 85.7% (1 8 /21 cases)patients within 4 -year -old children,and the median age was 23 months (2 -86 months).Fever and abdominal symptoms were the prominent clinical symptoms,52.4% (1 1 /21 cases)with fever,38.1 % (8 /21 cases)with abdominal dis-tention,diarrhea and other abdominal symptoms,80.5% (1 9 /21 cases)had splenomegaly (mild 1 9.1 %,middle 33.3%,severe 38.1 %),and some patients had other tissue infiltration,such as rash,yellow tumor and lymphnode enlargement.Peripheral blood cell count showed that the white blood cells increased because of anemia or thrombocyto-penia,ranging from 1 0.40 ×1 09 /L to 82.1 4 ×1 09 /L(median,26.1 0 ×1 09 /L),and the monocyte counts ranged from 1 .46 ×1 09 /L to 21 .60 ×1 09 /L(median,3.79 ×1 09 /L),characteristics of JMML gene abnormality was detected in 1 7 cases:including 1 1 single gene mutation,and 6 cases with double gene mutations.PTPN11 was the highest frequency of occurrence,accounting for 52.9% (9 /1 7 cases),and NF1 mutation was 35.3% (6 /1 7 cases).All the patients were followed up by phone call,the median follow -up time was 371 days (57 -562 days),6 patients were lost to follow -up,7 patients died,2 patients were alive after hematopoietic stem cell transplantation,1 patient converted to acute non lymphocytic leukemia,and 5 patients were still alive after receiving symptomatic treatment.Among dead cases,PTNT11 gene mutation and NF1 gene mutation were detected in 6 patients;among living children after hematopoietic stem cell transplantation,RAS and PTNT11 mutations were detected in 2 patients;among living children after symptomatic treat-ment,RAS mutation was detected in 2 patients and PTPN11 +CBL mutation in 1 case.Conclusions The symptom and laboratory examination of JMML have no specificistics,with poor prognosis,gene diagnose has guiding significance for JMML diagnose and for selecting therapy.
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Objective To investigate the clinical characteristics,treatment and prognosis of single-system Langerhans cell histiocytosis (LCH) in children.Methods A retrospective analysis was performed in single-system LCH patients registered between January 2006 and December 2012 in Beijing Children＇s Hospital Affiliated to Capital Medical University.The patients were divided into 2 groups:the bone involvement group and the other organ involvement group.The patients were assessed at 5 weeks,11 weeks,25 weeks,3 months,6 months,1 year and 3 years.The data were analyzed by using SPSS 17.0 software.Results A total of 112 patients (66 boys and 4,6 girls) with a median age of 5 years at diagnosis of LCH were analyzed.The most frequently affected organ was the bones(91 cases,81.3％),followed by skin(15 cases,13.4％).Few patients (27.6％) had acentral nervous system risk lesion,who were younger than those with other bone lesion(2.5 years vs 6.6 years).Patients with bone lesions were diagnosed at a significantly older age than other patients(5.6 years vs 1.5 years) (P ＜ 0.01).All patients received chemotherapy that included Prednisone and Vinblastine for 25 weeks.Twenty-five patients (22.3 ％) showed reactivation.Of these,4 patients exhibited reactivation in the pituitary.Three-year overall survival rate was expected to reach 100％,and no-event survival was expected at (73.22 ± 4.47) ％.Age of less than 2 years old was the factor of reactivation (P =0.033);sex,organ involvement and member of bone involved were not related with reactivation (P =0.679,0.142,0.639).Conclusions The bones were the frequent involvement organ in single-system LCH patients.These patients have a good prognosis.The rate of reactivation of single system-LCH can be decreased by chemotherapy.
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Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response.
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Objective To identify the relationship between sorafenib's efficacy and its side effects in treatment of advanced renal cell carcinoma patients. Methods Fifty-one patients having measurable diseases were diagnosed with advanced renal cell carcinoma. Of whom, 26 patients were in stage T1Nx,0,1M1, 12 patients in stage T2Nx,0 M1, 8 patients in stage T3NxM1, 5 patients in stage T4NxM1. These 46 patients of T1 -T3 had their primary diseases removed, but the 5 T~ patients didn"t have their primary diseases removed. These 51 patients received oral sorafenib 400 mg Bid continual-ly and they had CT scan every two months to evaluate the progression. The dosage of sorafenib wasmodified according to efficacy and toxicity. Two patients changed the dosage to 200 mg Bid due to se-vere side effects. Sixteen patients increased the dosage to 600 mg Bid or 800 mg Bid. The response ofSorafenib and toxicities as well as their severity were recorded. The toxicity severity was graded ac-cording to National Cancer Institute Common Toxicity Criteria version 3.0. The efficacy was deter-mined by RECIST criteria. The efficacy and progression free survival (PFS) were recorded. The sta-tistics analysis was conducted between sorafenib's side effects and efficacy as well as their severity by multi-faetor Logistic regression. Results The rates of adverse events in the patients receiving oral sorafenib were hand-foot skin reaetion 68. 6% (35/51), diarrhea 39. 2% (20/51), rash 25. 5% (13/ 51), mucositis 23.5% (12/51), hypertension 17.6% (9/51), and myelosuppression 13. 7%(7/51). The response rate in the patients who had toxicity of grade 3-4 was 33.3%(12/36), and that in the patients who had slight toxicity was 12.0%(3/25). The rate of hand-foot skin reaction was higher than that of diarrhea, rash, mucositis, hypertension and bone marrow suppression (P<0.01). Sor-afenib's efficacy was eorrelated to rash and mueositis (P=0.048, 0.045 respectively). More grade 3 4 side effects occurred in the patients who would have better response to sorafenib (P=0.008). The median PFS was 15.0 months and PFS was not related to the toxicity and its severity. Conclusions It may help to predict the response for sorafenib's side effects and efficacy in the treatment of the patients with advaneed renal cell earcinoma.