BACKGROUND:Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasm most commonly involving bone. However, data on single-system, single-site LCH (SS-s-LCH), particularly with unifocal bone disease, remain limited. Management strategies for unifocal osseous LCH vary globally, and the safety of a watchful-waiting approach is not well-defined. This study aimed to evaluate whether patients with osseous SS-s-LCH can be managed with observation alone without compromising long-term outcomes. METHODS:In this retrospective, multicenter study, we enrolled children with biopsy-proven osseous SS-s-LCH from 7 centers in the Chinese Children's Histiocytosis Group, excluding those with central nervous system (CNS)-risk bone lesions. The primary endpoint was 3-year event-free survival (EFS). Events were defined as disease progression or relapse. RESULTS:The cohort included 134 patients with a median follow-up of 36.0 months. Involved sites were cranial bones (n = 37), vertebrae (n = 33), and other bones (n = 64). At final follow-up, 16 patients experienced an event, yielding a 3-year EFS of 88.1% (95% CI: 81.5%-92.5%). Events included new lesions (n = 14) and primary lesion expansion (n = 2), with 93.8% (15/16) occurring within the first 12 months after diagnosis. EFS did not differ significantly by involved site or mutation status. However, patients staged by PET-CT at diagnosis had a significantly higher 3-year EFS (97.6%) than those staged by conventional imaging (83.7%) (P < .05). Long-term quality of life was satisfactory in all assessed patients. CONCLUSIONS:Watchful waiting is a safe and effective management strategy for children with unifocal osseous SS-s-LCH. Initial staging with PET-CT may be associated with superior EFS, highlighting its potential value in refining risk assessment.

Pediatric Castleman disease (CD) is a rare lymph node disorder, and renal involvement is uncommon in pediatric CD. This study aimed to investigate the clinical features of pediatric CD with renal involvement. Clinical data from Beijing Children’s Hospital for pediatric patients with CD were analyzed retrospectively. All included cases were confirmed by lymph node biopsy, with one patient also undergoing renal biopsy. A total of 42 pediatric patients with CD were included, of whom 20 (47.6

Iron deficiency anaemia (IDA) is the most prevalent nutritional deficiency among children globally. Intravenous (IV) iron serves as an alternative treatment for paediatric patients with poor response to oral iron therapy. However, data on the use of IV iron sucrose treatment in Chinese children remain limited. This retrospective study evaluated 40 paediatric patients with IDA (≤ 18 years) treated with IV iron sucrose at Beijing Children’s Hospital (July 2022-December 2023). Demographic, clinical, and laboratory parameters were analysed before and after therapy. Among the paediatric patients, 22 were male, 18 were female, and 19 were adolescent children older than 12 years. The average haemoglobin concentration increased from 75.6 g/L to 124.9 g/L, and the haematological response rates at both 4 and 8 weeks post-IV treatment were 100

Objective: To investigate the clinical features, pathological phenotype, treatment and prognosis of idiopathic multicenter Castleman disease (iMCD)in children. Methods:From January 2017 to September 2023, basic information, laboratory tests, treatment and prognosis of children diagnosed with iMCD who attended Beijing Children's Hospital of Capital Medical University were collected. Results: A total of 9 children were enrolled, with a median age of onset of median 11 (2-15) years, 6 males and 3 female. 3 cases were pathologically typed as plasma cell type, 1 case was mixed type, and the remaining 5 cases were hyaline vascular type. 9 children received different regimens of chemotherapy. The median follow-up time was 26 (13, 58) months, with no deaths, 7/9 cases showing improvement, 1/9 cases showing stable condition, and 1/9 cases showing active condition. Conclusion: Children with multicentric CD often have systemic symptoms, lymph node enlargement and related compression symptoms are the most common manifestations, followed by fever, malaise and other systemic symptoms. Anti-IL-6-based therapy combined with hormones lenalidomide and other medications have a specific therapeutic effect on multicentric CD.

The clinical manifestations of hereditary spherocytosis (HS) are often heterogeneous, spanning from asymptomatic to severe symptoms that may pose life-threatening risks. Genotype-phenotype correlations remain controversial in clinical research. This retrospective study evaluated the correlation between genetic variants and clinical characteristics in a cohort of 64 Chinese pediatric patients with HS. The predominant variants were found in the ANK1 (27 cases, 42%) and SPTB (26 cases, 41%) genes, while variants in the SPTA1 (6 cases, 9%) and SLAC4A1 genes (5 cases, 8%) were less common. No EPB42 variants were detected. A total of 71 variants were identified. Variation types included nonsense (21%), missense (27%), frameshift mutations (39%), splicing (8%), and large fragment deletions (4%). No statistical differences in hemoglobin levels, MCV, MCH, MCHC, or reticulocytes were observed across the various genetic variant groups. Bilirubin levels were remarkably elevated in patients with HS variants, and those with SPTB-HS had significantly higher bilirubin levels, including total bilirubin (p = 0.033) and indirect bilirubin (p = 0.018) compared to those with SPTA1-HS. Moreover, those with the ANK1 variants displayed reduced resistance to lysis at varying NaCl concentrations in comparison to those with the SPTA1 variants (p = 0.047). In short, patients with the ANK1 and SPTB variants had the most severe disease, while those with the SPTA1 variants had the mildest. Genetic testing is advised in patients without a family history or who are difficult to diagnose with routine laboratory tests, as this may also provide references for clinical treatment and genetic counseling.

BACKGROUND:Severe aplastic anemia (SAA) is caused by immune-mediated destruction. Standard immunosuppressive therapy (IST) is effective but needs to be improved. METHODS:The data of patients with SAA and received IST were analyzed retrospectively to conducted this historical control study. RESULTS:A total of 115 SAA patients (60 males; median age of 5.77 years and median follow-up time of 45 months) were enrolled in this study. The complete response rates (CRR) of the eltrombopag group at 3 and 6 months were higher than the control group (30.3% vs.8.2% at 3 months; 50.0% vs. 10.2% at 6 months). The overall response rates (ORR) showed no differences. There were significant differences in the times from G-CSF, Red blood cell transfusion, and Platelet transfusion between the two groups. No difference in overall survival (OS), event-free survival (EFS), and relapse rate between two groups. There is no variable were associated with prognosis in both groups. CONCLUSION:Addition of eltrombopag to IST confers faster hematological response and higher early hematological response in pediatric SAA patients. IMPACT:Addition of eltrombopag to standard immunosuppressive therapy confers faster hematological response and higher early hematological response in pediatric severe aplastic anemia patients. Eltrombopag showed reliable safety but had no impact on long-term response and prognosis. This article is a historical controlled study consisting of 115 pediatric severe aplastic anemia patients and makes up for the lack of clinical data deficient on pediatric severe aplastic anemia with TPO-RA combined with IST.

For autoimmune disease (AD) and autoinflammatory disease (AID)-related haemophagocytic lymphohistiocytosis (HLH) (AD/AID-HLH), there is still a lack of standardized treatment. Glucocorticoids (GCs) are the main treatment currently; however, 37.9% to 61% of patients fail to achieve effective control of HLH, making it urgent to find novel treatment strategies. We conducted a retrospective, single-centre study examining ruxolitinib (RUX)-based regimen in children with AD/AID-HLH. Patients were first treated with RUX monotherapy, and additional treatments including methylprednisolone and etoposide were added sequentially when the disease could not be controlled. The study included 26 patients with a median follow-up of 23.9 months, of whom 15 had prior treatments. The overall response rate at week 8 with the RUX-based regimen was 96.2%, with 92.3% attaining complete response (CR) and 3.9% attaining partial response. The 2-year overall survival rate was 96.2% (95% CI, 80.4% to 99.9%). During RUX monotherapy, 46.1% of patients achieved CR as the best response, with a median first response time to RUX of 2 days. Additionally, 53.8% of patients required additional GCs and 23.1% required etoposide chemotherapy. All observed adverse events were manageable and acceptable. Overall, our study supports the efficacy and safety of the RUX-based regimen in children with AD/AID-HLH.

IntroductionRiboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure red cell aplasia. Recognizing and understanding its clinical manifestations, diagnosis, and management is important.Case presentationA 2-year-old patient presented with pure red cell aplasia as the primary symptom of RTD. After confirming the diagnosis, rapid reversal of anemia was achieved after high-dose riboflavin treatment.ConclusionRTD often has an insidious onset, and neurological symptoms appear gradually as the disease progresses, making it prone to misdiagnosis. Genetic testing and bone marrow biopsy can confirm the diagnosis.

Thrombopoietin (TPO) is the critical regulator of platelet production. However, the role of TPO in pediatric patients with thrombocytopenic disorders has not been fully elucidated. In the present study, we attempted to investigate serum TPO levels in patients with acquired aplastic anemia (aAA) and immune thrombocytopenia (ITP). We analyzed the endogenous plasma concentration of TPO and platelet count at the time of TPO measurement in 166 patients with aAA and 280 patients with ITP retrospectively. We further observed a correlation between platelet counts and TPO. Serum TPO levels were significantly higher in aAA compared with ITP (1142 vs. 77.99 pg/mL, P <0.001). In patients with aAA, an elevation for TPO levels in very severe AA (VSAA) was seen when compared with non-severe AA (NSAA) (1360 vs. 984.4 pg/mL, P <0.05). In contrast, the circulating TPO levels with chronic ITP (CITP) showed a decrease than newly diagnosed ITP (NITP) and persistent ITP (PITP) (62.28 vs. 81.56 pg/mL, P <0.01, 62.28 vs. 87.82 pg/mL, P <0.05, respectively). There was a negative correlation between platelet counts and TPO levels in aAA (r s =−0.3325, P <0.001) as well as ITP (r s =−0.2570, P <0.001). Especially, TPO levels were inversely correlated with platelet counts in NSAA (r s =−0.3672, P <0.001) and NITP (r s =−0.3316, P <0.001). After grouping by age or sex, there were no statistical differences in aAA or ITP. Serum TPO levels were markedly elevated in pediatric patients with aAA compared with ITP. It was higher in VSAA and lower in CITP, suggesting that serum TPO level could play a role in classifying disease severity or clinical course in aAA and ITP.

1 病例资料 病例1:男,12岁,主诉"左下肢水肿4年余,反复感染、血细胞减少1年余"(图1).入院辅助检查:(1)血常规:白细胞1.62×109/L,中性粒细胞59％,淋巴细胞36％,单核细胞1％,血红蛋白98g/L,血小板127×109/L.(2)外周血淋巴细胞绝对值0.53×109/L,总T淋巴细胞764个/uL,总B淋巴细胞2个/uL,NK细胞23个/uL,CD4/CD8比值0.64.(3)骨髓穿刺细胞学:增生活跃,粒系增生减低,粒红比例明显减低(0.25),巨核细胞不减少.骨髓活检:有核细胞增生＜10％,脂肪细胞增生,少数偏成熟阶段的粒、红细胞散在分布,未见巨核细胞.

目的 旨在比较序贯大剂量地塞米松、利妥昔单抗免疫抑制治疗后加用艾曲波帕与直接应用艾曲波帕治疗的儿童慢性免疫性血小板减少症(CITP)数据,证实免疫抑制基础上的促血小板生成治疗可提高儿童CITP疗效.方法 本研究为单中心非随机对照研究,将2018年1月-2021年8月入组的CITP患儿分为两组:(1)直接应用艾曲波帕(简称直接组);(2)经大剂量地塞米松、利妥昔单抗升阶梯治疗无效时加用艾曲治疗(简称序贯组).评价两组疗效、安全性和药物经济学指标.结果 共入组48例患儿,男性23例,女性25例,中位发病年龄为5.0(3.6-7.5)岁,病程均超过一年,治疗前血小板(PLT)计数为10.0(4.0-15.0)×109/L.(1)基线数据:直接组男16例,女13例,序贯组男7例,女12例.两组的发病年龄、病程、PLT计数等基线无统计学差异(P＞0.05).(2)疗效:直接组的总体反应率为69％,完全反应率21％,无效率31％;序贯组分别为84％、26％和16％.直接组艾曲波帕平均治疗时长为8.2个月,停药率41％,62％的患儿PLT水平维持在50×109/L以上水平,平均治疗费用为7.38万元;序贯组艾曲波帕平均治疗时长为7.0个月,停药率58％,74％的患儿PLT维持在50×109/L以上,平均治疗费用为9.87万元;停药率及PLT维持在50×109/L以上的患儿比例,序贯组均高于直接组,但不存在统计学差异.(3)安全性:直接组药物相关不良事件3例(10％),序贯组8例(42％),无统计学差异(P＞0.05).结论 与直接应用艾曲波帕治疗儿童CITP相比,在免疫抑制剂治疗基础上应用艾曲波帕,疗效更好且不增加副作用和经济负担,可考虑作为儿童CITP二线治疗的优选策略.

Pediatric Blood & CancerEarly View e30010 LETTER TO THE EDITOR Anaplastic lymphoma kinase positive histiocytosis presenting as hemocytopenia in an infant Wenqian Wang, Wenqian Wang orcid.org/0000-0002-2057-4920 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorLejian He, Lejian He Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorRunhui Wu, Runhui Wu orcid.org/0000-0003-4030-209X Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorJiafeng Yao, Jiafeng Yao Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorHonghao Ma, Honghao Ma Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorXiaoling Cheng, Xiaoling Cheng orcid.org/0000-0002-0048-2658 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorAng Wei, Ang Wei orcid.org/0000-0002-7046-2417 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorHongyun Lian, Hongyun Lian Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorDong Wang, Dong Wang Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorZhigang Li, Zhigang Li Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing, ChinaSearch for more papers by this authorTianyou Wang, Tianyou Wang Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorRui Zhang, Corresponding Author Rui Zhang ruizh1973@126.com orcid.org/0000-0001-7982-4165 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China Correspondence Rui Zhang, Department of Hematology, Beijing Children's Hospital, Capital Medical University, Nanlishi Road No. 56, Xicheng District, Beijing 100045, P.R. China. Email: ruizh1973@126.comSearch for more papers by this author Wenqian Wang, Wenqian Wang orcid.org/0000-0002-2057-4920 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorLejian He, Lejian He Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorRunhui Wu, Runhui Wu orcid.org/0000-0003-4030-209X Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorJiafeng Yao, Jiafeng Yao Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorHonghao Ma, Honghao Ma Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorXiaoling Cheng, Xiaoling Cheng orcid.org/0000-0002-0048-2658 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorAng Wei, Ang Wei orcid.org/0000-0002-7046-2417 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorHongyun Lian, Hongyun Lian Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorDong Wang, Dong Wang Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorZhigang Li, Zhigang Li Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing, ChinaSearch for more papers by this authorTianyou Wang, Tianyou Wang Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, ChinaSearch for more papers by this authorRui Zhang, Corresponding Author Rui Zhang ruizh1973@126.com orcid.org/0000-0001-7982-4165 Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China National Key Discipline of Pediatrics, Capital Medical University, Beijing, China Key Laboratory of Major Disease in Children, Ministry of Education, Beijing, China Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China Correspondence Rui Zhang, Department of Hematology, Beijing Children's Hospital, Capital Medical University, Nanlishi Road No. 56, Xicheng District, Beijing 100045, P.R. China. Email: ruizh1973@126.comSearch for more papers by this author First published: 02 October 2022 https://doi.org/10.1002/pbc.30010Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Supporting Information Filename Description pbc30010-sup-0001-figureS1.tif123.1 KB Supplemental figure S1 Sequencing results confirmed the ALK-CLTC gene fusion. 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Objective: LPS-responsive beige-like anchor (LRBA) deficiency is one of the most common monogenic disorders causing common variable immunodeficiency (CVID) and CVID-like disorders. However, the clinical spectrum of compound heterozygous (CHZ) LRBA variation should be extended. In this study, we presented five cases of compound heterozygous LRBA with various refractory cytopenias. Materials and Methods: Retrospective analysis of the clinical manifestations, management, and outcomes of five cases (from five pedigrees) with LRBA gene CHZ variants which initially manifested as single/multilineage immune cytopenias was performed. Results: 1. Gene variations: All five patients inherited the compound heterozygous LRBA variations from their parents which were thought to be pathogenic. BEACH, DUF4704, and LamG were the main affected domains of LRBA gene in this case series. 2. Immune dysregulation of clinic: (1) Hypogammaglobulinemia were recorded in four patients, and the proportion of Treg was decreased in two patients. Only one patient had been with increased TCRαβ+CD4/CD8 double-negative T cells (DNT). (2) Lymphoproliferative manifestations were seen in three patients. (3) All five patients were complained with cytopenia, although they showed different clinical manifestations. None of the parents was asymptomatic. (4) Other immune disorders: P5 also had relapsed infections and autoimmune endocrinopathy. 3. Management and outcomes: P1 and P5 responded well to immunomodulatory therapy and P3 was effectively treated with hemophagocytic lymphohistiocytosis (HLH) first-line regimen chemotherapy. P4 showed no responses to steroids and IVIG. However, TPO-R agonist was effective. Conclusion: Unlike homozygous mutations, compound heterozygous LRBA variation should always be kept in mind for the various phenotypes and different treatment responses.

Abstract Ras-associated autoimmune leukoproliferative disease (RALD) is a clinical syndrome, also known as autoimmune lymphoproliferative syndrome (ALPS) type IV, which is a primary immunodeficiency disease. However, there is still controversy about whether RALD is a chronic benign lymphoproliferative disease or a precancerous lesion. The clinical characteristics, laboratory examination results, treatment and prognosis of children with RALD treated in Beijing Children's Hospital were analyzed retrospectively. We reported 13 patients with RALD in our single center. The male-to-female ratio was 1.6:1, and the median age of onset was 6 months (range 2 months- 29 months). Eight patients (61.5%) had KRAS somatic mutations, and five patients (38.5%) had NRAS somatic mutations. The most common features were splenomegaly (12/13 cases), autoimmune cytopenia (9/13 cases), mononucleosis (10/13 cases), recurrent infection (7/13 cases), skin involvement (4/13 cases) and intestinal lesions (4/13 cases). Thirteen children were treated with immunotherapy, including glucocorticoids, intravenous immunoglobulin, cyclosporine, and sirolimus. The median follow-up time was 50 months (range 3 months-62 months). Four children died (2 cases of respiratory failure, 1 case of intestinal perforation and bleeding, and 1 case of sepsis with sudden respiratory and cardiac arrest). Nine children survived, seven children were treated with sirolimus, and no children developed malignant tumors of the hematopoietic system. In conclusion, RALD requires long-term follow-up to monitor malignant tumors, and sirolimus is effective for treatment.

A 6-year-old girl presented with recurrent skin rash at the initial stage, recent joint pain, and neutrophilia was found during a routine blood test. After a multidisciplinary case discussion, she was diagnosed with chronic neutrophil leukemia, and the symptoms were relieved after hydroxyurea and luxolitinib treatment. She received the allogeneic hematopoietic stem cell transplantation subsequently. At present, she is in stable condition and under follow-up. Chronic neutrophil leukemia is a rare disease, which rarely occurs in children. It is more difficult to diagnose in patients with skin rash as the first manifestation. The diagnosis and treatment of this case reflects the important role of multidisciplinary cooperation in the diagnosis and treatment of difficult and rare diseases.

Objective: LPS-responsive beige-like anchor (LRBA) deficiency is one of the most common monogenic disorders causing common variable immunodeficiency (CVID) and CVID-like disorders. However, the clinical spectrum of compound heterozygous (CHZ) LRBA variation should be extended. In this study, we presented five cases of compound heterozygous LRBA with various refractory cytopenias. Materials and Methods: Retrospective analysis of the clinical manifestations, management, and outcomes of five cases (from five pedigrees) with LRBA gene CHZ variants which initially manifested as single/multilineage immune cytopenias was performed. Results: 1. Gene variations: All five patients inherited the compound heterozygous LRBA variations from their parents which were thought to be pathogenic. BEACH, DUF4704, and LamG were the main affected domains of LRBA gene in this case series. 2. Immune dysregulation of clinic: (1) Hypogammaglobulinemia were recorded in four patients, and the proportion of Treg was decreased in two patients. Only one patient had been with increased TCRαβ+CD4/CD8 double-negative T cells (DNT). (2) Lymphoproliferative manifestations were seen in three patients. (3) All five patients were complained with cytopenia, although they showed different clinical manifestations. None of the parents was asymptomatic. (4) Other immune disorders: P5 also had relapsed infections and autoimmune endocrinopathy. 3. Management and outcomes: P1 and P5 responded well to immunomodulatory therapy and P3 was effectively treated with hemophagocytic lymphohistiocytosis (HLH) first-line regimen chemotherapy. P4 showed no responses to steroids and IVIG. However, TPO-R agonist was effective. Conclusion: Unlike homozygous mutations, compound heterozygous LRBA variation should always be kept in mind for the various phenotypes and different treatment responses. Keywords LPS-responsive beige-like anchor deficiency , common variable immunodeficiency , autoimmune lymphoproliferative syndrome , hypogammaglobulinemia , immunomodulatory therapy