Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis / 中华儿科杂志

Objective: To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH). Methods: This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children's hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate. Results: Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive. Conclusions: For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Efficacy and safety of intermediate-dose cytarabine in the treatment of children with refractory high risk Langerhans cell histiocytosis / 中华儿科杂志

Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m2, twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.

Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). @*Materials and Methods@#A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. @*Results@#The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. @*Conclusion@#Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Central Nervous System Involvement in 179 Chinese Children with Hemophagocytic Lymphohistiocytosis / 中华医学杂志(英文版)

Background@#Central nervous system (CNS) involvement is found in many patients with hemophagocytic lymphohistiocytosis (HLH). In this study, we mainly analyzed neurological symptoms, imaging findings, cerebrospinal fluid (CSF), and their relationship with outcomes of HLH children.@*Methods@#Related data of 179 Chinese pediatric patients with HLH admitted to our center from January 2010 to December 2015 were analyzed retrospectively. Diagnosis and treatment were based on the HLH-2004 protocol. Two-tailed Chi-squared test was used to compare between different groups, and Kaplan-Meier survival curves were used to analyze the overall survival (OS) of patients with HLH.@*Results@#In the present study, 21.2% (38/179) of total patients had neurological symptoms including seizure, irritability, somnolence, and unconsciousness. There were 80 (50.0%, excluding 19 patients without imaging data) patients with cranial imaging abnormalities. There were 14.7% (17/116, excluding 63 patients who did not accept lumbar puncture) of patients with abnormal CSF results. CNS involvement is defined as abnormalities in one or more of CNS symptoms, radiological findings, and CSF. Thus, 60.3% of them had CNS involvement. As for the prognosis, the median follow-up time was 3.2 years (17 lost to follow-up). The probable 3-year OS of children was higher without CNS involvement (86.0% ± 4.6%) than those with CNS involvement (68.9% ± 4.9%, hazard ratio [HR] = 2.286, P = 0.019). Among them, the probable 3-year OS of children without CNS symptoms was 76.0% ± 3.8%, higher than with CNS symptoms (59.5% ± 8.1%, HR = 2.147, P = 0.047). The 3-year OS of children with abnormal CSF was 64.7% ± 11.6%, compared with normal CSF (85.1% ± 3.7%, HR = 0.255, P = 0.038).@*Conclusions@#HLH patients with CNS involvement might have worse outcomes compared with those without CNS involvement, and CNS symptoms and CSF changes are more important to access the prognosis than imaging abnormality.

Clinical Research of Pulmonary Langerhans Cell Histiocytosis in Children / 中华医学杂志(英文版)

Background@#Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial primary pulmonary disease, characterized by Langerhans cell proliferation. It is easily misdiagnosed in children. This study aimed to characterize the clinical manifestations and features of PLCH by retrospective analysis.@*Methods@#A retrospective analysis was performed in 117 PLCH patients out of 338 LCH patients who were admitted in our center from November 2006 to October 2013. Variables between two groups were compared by Mann-Whitney U-test and Chi-square test. Kaplan-Meier curves were constructed to compare the survival rates and Cox regression to evaluate the effect of risk factors.@*Results@#The median age of PLCH group was significantly lower than that of non-PLCH group (18.63 months vs. 43.4 months, P < 0.001). All PLCH children had other organ involvement and only 11 cases (9.4%) had respiratory symptoms. The most common radiologic finding was cystic lesions (29 cases, 24.8%). Pulmonary function abnormalities were dominated by obstructive ventilatory dysfunction (63 cases, 82.9%). The 5-year overall survival (OS) of PLCH children was 93.6% ± 2.3% and the event-free survival (EFS) was 55.7% ± 5.2%. Among the 38 cases with progressed or relapsed disease, five cases (13.2%) were due to progression or recurrence of lung damage. The 5-year OS of PLCH children with "risk organ" involvement was significantly lower than those without "risk organ" involvement (86.0% ± 4.9% vs. 100%, χ = 8.793, P = 0.003). The difference of EFS between two groups was also significant (43.7% ± 7.7% vs. 66.3% ± 6.5%, χ = 5.399, P = 0.020). The "risk organ" involvement had a significant impact on survival (hazard ratio = 1.9, P = 0.039).@*Conclusions@#PLCH mainly occurs in young children, and only a small percentage of patients have respiratory symptoms. They generally have other organ involvement. Most of PLCH children have a good prognosis and most lung lesions could have improved or stabilized. Management of "risk organ" involvement is the key point to improving EFS.

Observation of Efficacy and Safety of Chemotherapy on Hemophagocytic Lymphohistiocytosis with Hepatic Dysfunction in Children / 实用儿科临床杂志

Objective To preliminarily evaluate the efficacy and safety of chemotherapy on hemophagocytic lymphohistiocytosis(HLH) with hepatic dysfunction in children.Methods The children diagnosed as non-malignancy-associated HLH from Mar.2004 to Apr.2008 were selected,and the therapeutic effect was evaluated according to the HLH-04 protocol at the 8th week of chemotherapy,and the level of serum alanine aminotransferase(ALT),serum albumin(Alb) and plasma fibrinogen(Fib) were detected at pretherapy,2 weeks and 8 weeks of post-treatment.Results Altogether 60 HLH children complicated with hepatic dysfunction before chemotherapy,47 children had increased ALT,58 children had decreased Alb,and 38 children had decreased Fib.Forty-two cases(70%) were virus-associated HLH,1 case(1.7%) was fungi-associated HLH,and 17 cases(28.3%) had unknown origin.Among the 60 children,55 cases showed improvement in the 4 weeks of inductive treatment,15 cases gave up therapy,45 cases completed the 8 weeks of inductive treatment according to the protocol(among these children,42 cases had no active disease,3 cases had active disease),and these 45 children had obviously improved ALT,Alb and Fib at 2 weeks and 8 weeks of post-treatment,compared with pretherapy,the differences had statistical significance(Pa