Ruxolitinib Monotherapy for a Child With HAVCR2 Gene Mutation Associated Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Case Report.

BACKGROUND: The occurrence of hemophagocytic lymphohistiocytosis (HLH) in patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) may be due to HAVCR2 gene mutation, leading to T-cell immunoglobulin and mucin domain-containing molecule 3 deficiency, T-cell and macrophage activation, and proinflammatory cytokine production. OBSERVATION: We report a patient with SPTCL and HLH for whom ruxolitinib, used as a novel treatment, showed notable therapeutic effects. CONCLUSIONS: Remission of both HAVCR2 mutation-induced high inflammatory characteristics and significant symptoms post-ruxolitinib administration suggested that patients with SPTCL and HLH may not represent typical lymphoma cases. Ruxolitinib, with its relatively low toxic side effects, can provide favorable outcomes.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Animal study: Basic mechanism of vocal cord paralysis caused by button battery ingestion in children.

PURPOSE: Vocal cord paralysis has been reported as a common complication of button battery (BB) ingestion, and there is a need to confirm the mechanism of vocal cord paralysis for the development of a standardized treatment. METHODS: A new CR2032 BB and artificial saliva were placed in a fresh pig esophagus with the recurrent laryngeal nerve (RLN); the negative electrode faced the nerve in the experimental group, while the positive electrode faced the nerve in the control group. The pH values of the intra- and extraesophageal walls were measured simultaneously. Pathological examination was performed after the esophagus and nerves were damaged. RESULTS: After BB ingestion, the pH near the intraesophageal negative electrode increased rapidly, reaching 11.5 at 30 min and over 14 at 6 h, while the extraesophageal pH did not change at 1 h and began to accelerate after 2 h, reaching 10 at 6 h. After 6 h of exposure, the pathological section showed that the structure of the mucosa, submucosa, and muscle layer were destroyed; chromatin in the nucleus faded, and part of the nerve bundle in the adventitia had liquefaction necrosis. CONCLUSION: The basic mechanism of vocal cord paralysis caused by BB ingestion is that the OH- generated by the electrolytic reaction of the negative electrode penetrates the esophageal wall and corrodes the RLN, which may be the cause of vocal cord paralysis caused by BB ingestion without esophageal perforation.

Contributions of glume and awn to photosynthesis, 14C assimilates and grain weight in wheat ears under drought stress.

Ear photosynthesis plays a key role in wheat photosynthesis during the grain filling stage, particularly under drought stress. Thus, dissecting the responsibilities of the glume and awn in photosynthetic carbon fixation and assimilates transportation during the grain filling stage in spikes is imperative. In this study, the detachment of the glume (DG) and awn (DA) of a wheat variety (Pubing143) was used to estimate their influences on ear photosynthesis and dry matter distribution. Radioactive carbon-14 (14C) isotope was detected by a multifunctional liquid scintillation counting system. The accumulation of 14C assimilates and their contributions to grain weight were then calculated. Under well-watered conditions, ear photosynthesis was reduced by 16.8 % and 46.2 % 25 d after anthesis (DAA) in the de-glumed control (DGC) and de-awned control (DAC) treatments, respectively, compared with the intact ear control (IEC). Under drought stress, ear photosynthesis was reduced by 46 % and 74.2 % at 25 DAA after removing the glume and awn, respectively. Under normal conditions, the number of 14C assimilates of DGC, and DAC was reduced by 14.6 % and 20.9 % in grains at 25 DAA, respectively, compared with the IEC. Compared with IED, the 14C assimilates of DGD, and DAD declined by 17.2 % and 27 %, respectively, in grains at 25 DAA under drought conditions. Under well-watered conditions, the grain weight per pot was reduced by 11.2 % and 25.4 % in the de-glumed control (DGC) and de-awned control (DAC) treatments, respectively, compared with the intact ear control (IEC). The grain weight per pot was further reduced after removing the glume and awn (16 % and 32.2 %, respectively) under drought stress. Furthermore, the awn contribution to grain weight was twice that of the glume. Our results suggest that the glume and awn of ears play prominent roles during grain filling in wheat, especially under drought stress, and that the awn is more crucial than the glume.

Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms.

Objective: To retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China. Methods: A retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis. Results: In total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common. Conclusion: The accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

[Effects of combined application of biochar and nitrogen fertilizer on soil quality of summer maize-winter wheat system]. / ç”Ÿç‰©ç‚­å’Œæ°®è‚¥é æ–½å¯¹å¤çŽ‰ç±³-冬小麦轮作体系耕层土壤质量的影响.

The effects of nitrogen fertilizer and biochar on topsoil quality in the drylands of northwest China were studied in field trials for two years. A split plot design with two factors was adopted, with five nitrogen rates (0, 75, 150, 225 and 300 kg N·hm-2) as main plots, and two rates of biochar (0 and 7.5 t·hm-2) as submain plots. We collected soil samples at 0-15 cm depth after two years of winter wheat-summer maize rotation and measured physical, chemical, and biological properties. The minimum data set (MDS) was established by using principal component analysis and correlation analysis to analyze the responses of soil quality to nitrogen fertilizer and biochar addition. The results showed that the combined application of nitrogen fertilizer and biochar could improve soil physical properties, increase macroaggregate content, reduce soil bulk density, and increase soil porosity. Both fertilizer application and biochar application had a significant effect on soil microbial biomass carbon and nitrogen. The application of biochar could improve soil urease activity and the contents of soil nutrients and organic carbon. Six out of 16 indicators (urease, microbial biomass carbon, total phosphorous, total nitrogen, pH, and available potassium) relating to soil quality were used to construct MDS, and soil quality index (SQI) was calculated. The variation range of SQI was 0.14-0.87, with that of 225 and 300 kg N·hm-2 nitrogen application combined with biochar application being significantly higher than other treatments. Soil quality could be significantly improved by application of nitrogen fertilizer and biochar. Interactive effect was observed, which was particularly stronger under high nitrogen application rate.

A retrospective study of 18 children with subcutaneous panniculitis-like T-cell lymphoma: multidrug combination chemotherapy or immunomodulatory therapy?

BACKGROUND: Subcutaneous panniculitis T-cell lymphoma (SPTCL) is a rare, cytotoxic T-cell lymphoma with which some patients have accompanying hemophagocytic syndrome (HPS). There is currently no standard treatment regimen. In the past, the most commonly used treatment was multidrug chemotherapy. In contrast, numerous case reports or small series suggest that immunosuppressive drugs could also be effective for some patients. Since this NHL subtype is extremely rare in children and adolescents, to improve the understanding of this disease and standardize its rational treatment, we retrospectively summarized the treatment regimens of 18 pathologically diagnosed children with SPTCL to compare the clinical efficacy of multidrug chemotherapy and immunomodulatory therapy. RESULTS: The median age of onset was 11.1 years. Painless subcutaneous nodules or skin patchy lesions were found in all patients, most commonly involving the lower extremities and/or trunk. Before January 1, 2019, the treatment was mainly chemotherapy, and 10 patients were initially treated with chemotherapy, among whom was one patient who progressed during initial treatment, was voluntarily discharged and was subsequently lost to follow-up, one patient who died of disease progression, and the remaining 8 patients who all achieved sustained remission, with a complete remission (CR) rate of 80% (8/10). Corticosteroids combined with cyclosporine A or ruxolitinib were the most common initial immunosuppressive agents at our center after January 1, 2019 and had a CR rate of 71.4% (5/7). In addition, 1 patient achieved partial remission (PR) during follow-up, and one had autologous hematopoietic stem cell transplantation (AHSCT) after 4 months of drug withdrawal. There were 7 patients (38.9%, one case in chemotherapy group and six cases in immunotherapy group) with HPS and 4/5 screened patients (80%) with positive HAVCR2 gene mutations. The median follow-up was 17 months. CONCLUSION: The prognosis of SPTCL is relatively good. Previous multi-drug and long-term chemotherapy treatment has clear efficacy, and recent immunomodulatory therapy as pre-chemotherapy therapy can also benefit patients.

Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients. RESULTS: LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034). CONCLUSIONS: LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.

[Effect of Film Mulching, Straw Retention, and Nitrogen Fertilization on the N2O and N2 Emission in a Winter Wheat Field].

In order to explore the characteristics of N2O emissions from winter wheat fields in the Loess Plateau under different farming methods and nitrogen levels, the dynamic changes in N2O emissions from rain-fed winter wheat fields were quantified using static box-gas chromatography. Winter wheat 'Xiaoyan22' was used as the material, and a two-factor split area design was adopted. The conventional tillage (CT), straw incorporated into soil (SM), and flat film mulching (FM) were assigned as the main plot, and three nitrogen fertilizer rates (no nitrogen fertilization, 20% nitrogen reduction (144 kg·hm-2), and conventional nitrogen application (180 kg·hm-2)) were assigned as a split plot. Taking CT as a control, the effects of FM and SM on soil N2O emissions under different nitrogen rates were assessed. Furthermore, the correlation between relevant environmental factors and N2O emission flux were analyzed, and N2 emissions were estimated using empirical formulas. The results showed the following:the N2O emissions from the soil of each nitrogen treatment occurred within 20 days, and N2O emission flux peaked within two weeks post-fertilization. The average N2O flux, the total N2O emissions, and the global warming potential of N2O were 1.92-22.75 µg·(m2·h)-1, 0.10-0.46 kg·hm-2, and 26.72-122.15 kg·hm-2, respectively. The N2O emission coefficient of fertilizer nitrogen was 0.05%-0.28%. The total N2 emissions ranged from 0.70-1.82 kg·hm-2. The N fertilization and film mulching significantly increased the N2O emission flux (P<0.05) and the cumulative N2O emissions (P<0.05); however, SM marginally reduced the total N2O emissions. The N2O emission coefficient and global warming potential of fertilizer nitrogen under FM were significantly higher than those under CT and SM (P<0.05). The N2O emissions without nitrogen treatment were only significantly positively correlated with soil water-filled pore spaces (WFPS) (P<0.05); the N2O emissions in the N fertilization condition were significantly positively correlated with WFPS, ω(NO3--N), ω(NH4+-N), and 0-5 cm soil layer temperature (P<0.05). Overall, under the condition of no fertilization, water was the main factor to control the nitrogen transformation and soil N2O emission; nevertheless, under the N fertilization condition, both nitrification and denitrification contributed to the N2O emissions in the rain-fed winter wheat fields. Film mulching practice and nitrogen application markedly increased the N2O emissions, fertilizer nitrogen emission coefficient, and global warming potential in the rain-fed winter wheat fields. Nonetheless, straw incorporated into the soil resulted in a marginal reduction in N2O emissions.

Predictive Significance of Enhanced Level of Angiogenesis and Tissue Neutrophils for Antrochoanal Polyps Recurrence in Children.

BACKGROUND: The pathologic features and potential predictive biomarkers for recurrence of antrochoanal polyps (ACPs) in children are not fully understood. OBJECTIVES: To identify the pathologic differences between recurrent and nonrecurrent group and to explore potential clinical markers which predict recurrence of ACPs in children. MATERIAL AND METHODS: A total of 11 recurrent and 21 nonrecurrent ACPs children were enrolled into this retrospect study. Clinical basic information was collected before the first surgery. The counts of vessels were evaluated by hematoxylin-eosin (HE) staining, and CD34 was detected by immunohistochemistry. Meanwhile, the percentage of each tissue inflammatory cells (eosinophils, neutrophils, lymphocytes, and plasma cells) was assessed by HE staining. RESULTS: No statistical significance was observed between the 2 groups in the basic clinical features. Moreover, both the counts of blood vessels and the tissue neutrophils percentage were enhanced significantly in group with ACPs recurrence (P < .05). According to the receiver operating characteristic curves, the area under the curve for the counts of blood vessels and tissue neutrophils percentage in the prediction of ACPs' recurrence was 0.779 (P = .0105) and 0.989 (P < .0001) respectively. CONCLUSIONS AND SIGNIFICANCE: It was concluded that the counts of blood vessels and the percentage of tissue neutrophils appeared to be potential excellent predictors of ACPs recurrence in children.

Sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma.

Single antigen-targeted chimeric antigen receptor (CAR) T-cell therapy may be insufficient to induce a durable response in pediatric aggressive B-cell lymphomas. This clinical trial examined the feasibility of sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric relapsed/refractory (R/R) Burkitt lymphoma. Twenty-three patients received the first CD19 CAR T-cell infusion. The patients who did not achieve an ongoing complete response (CR) underwent 1 or more sequential infusions of CAR T-cell therapy that targeted CD22 followed by CD20 according to their disease status and CAR T-cell persistence after each infusion. The median time from the last infusion to the cutoff date was 17 months (range, 15-23 months). The estimated 18-month CR rate was 78% (95% confidence interval [CI], 54%-91%). The estimated 18-month progression-free survival rate was 78% (95% CI, 55%-90%), with 78% (95% CI, 37%-94%) in patients with bulky disease and 60% (95% CI, 25%-83%) in patients with central nervous system (CNS) involvement. During the first CD19 CAR T-cell infusion, grade ≥3 cytokine release syndrome (CRS) occurred in 34.8% and neurotoxicity occurred in 21.7% of all patients. During subsequent infusions, there were only a few incidences of grade >2 CRS and neurotoxicity. All adverse events were reversible. The severity of neurotoxicity was not significantly different between patients with CNS involvement and those who did not have CNS involvement. Sequential CAR T-cell therapy may result in a durable response and is safe in pediatric R/R Burkitt lymphoma. Patients with CNS involvement may benefit from sequential CAR T-cell therapy. This trial was registered at www.chictr.org.cn/index.aspx as #ChiCTR1800014457.

Extraskeletal Ewing's Sarcoma with CD7 Positivity and T-cell Receptor/Immunoglobulin Rearrangement Masquerading as T-lymphoblastic Lymphoma.

Background: Extraskeletal Ewing's Sarcoma (EES) may harbor more than one tumor-specific genetic abnormality, leading to diagnostic difficulties. Case report: We report a nine-year-old boy with recurrent mass of his right thigh. Tumor cells were round, with scant cytoplasm, finely dispersed chromatin, and inapparent, small nucleoli. The initial misdiagnosis was T-lymphoblastic lymphoma due to CD7 and TCR/Ig monoclonal rearrangement. As it expressed NKX2.2 and harbored an EWSR1-FLI1 fusion transcript, the diagnosis was changed to EES. The child underwent EES therapy with good initial response, but had a subcutaneous relapse at 22 months. Conclusion: In addition to typical genetic alterations, Ewing sarcoma can also express CD7 and TCR/Ig rearrangement, which are not limited to lymphoma.

Primary central nervous system lymphoblastic B cell lymphoma located at cerebellum in a child: A case report and literature review.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is extremely rare in pediatric population. We reported a case of PCNSL in a 3-year-old girl and reviewed the literature in the past three decades. CASE PRESENTATION: A 3-year-old girl presented with gait disturbance. A contrast-enhanced magnetic resonance image of the brain showed a solitary bulky mass in the left cerebellar hemisphere, hydrocephalus and cerebellar tonsillar hernia. Surgical resection was performed and the patient was diagnosed with primary central nervous system lymphoblastic B cell lymphoma. Then the patient received regular chemotherapy, including 6 cycles of chemotherapy containing high-dose methotrexate (HD-MTX). The patient remains alive 15 months after the diagnosis with no evidence of active disease, but suffered twice chronic subdural hematoma, which was treated by burr hole drainage. CONCLUSION: Lymphoblastic B cell lymphoma is a rare histologic subtype of pediatric PCNSL. Chemotherapy containing HD-MTX remains the most effective treatment. The patient should avoid head impact after surgical resection of the tumor to prevent chronic subdural hematoma.

[Case Report: Three Pediatric Pulmonary Cryptococcosis Patients with Prominent Manifestation of Mediastinal Lymphadenopathy].

In this study, we report on three immunocompetent children with pulmonary cryptococcosis presenting mediastinal lymphadenopathy as the prominent manifestation. All three children were otherwise healthy previously. Two children had a history of exposure to pigeons and poultry. All three presented persistent fever accompanied by mild cough. There were no obvious positive signs in the lungs. One patient had enlarged cervical lymph nodes. All three had elevated levels of white blood cells, neutrophil count, and C-reactive protein (CRP). The levels of IgG, IgM, IgA, IgE and T cell subsets were normal in all cases, and they were all tested negative for HIV antibody. Two children were tested positive for serum cryptococcal antigen (sCRAG). The chest X-ray and pulmonary CT findings of the three patients all demonstrated marked enlargement of mediastinal lymph nodes, and one patient had nodules in the parenchyma. Surgical biopsies of mediastinal lymph nodes were performed in two children and large numbers of capsule spores were found in the histological examination. In the three cases, definitive diagnosis of pulmonary cryptococcosis were made in two patients, and clinical diagnosis was made in the third patient. Two patients were treated with fluconazole alone. The other patient whose condition was complicated with spleen infection was treated with fluconazole combined with amphotericin B for the first month, and was then given fluconazole for maintenance treatment. The overall treatment course lasted 5-9 months and all three were cured eventually. In conclusion, immunocompetent children with pulmonary cryptococcosis may present mediastinal lymphadenopathy as a prominent or isolated manifestation, which should be considered in differential diagnosis. Treatment with fluconazole alone or in combination with amphotericin B when it was necessary showed good therapeutic outcomes.

Diagnosis and treatment of pediatric anaplastic lymphoma kinase-positive large B-cell lymphoma: A case report.

BACKGROUND: Anaplastic lymphoma kinase-positive (ALK+) large B-cell lymphoma (LBCL) is a rare type of lymphoma with high invasiveness and rapid progression. It occurs in all age groups, but is extremely rare in children. The lesions mainly involve the lymph nodes and may present with extra-nodal involvement. Response to conventional chemotherapies and local radiotherapy is poor, with a 5-year overall survival of less than 40%. Recently, the use of ALK inhibitors for the treatment of this disease has been reported. CASE SUMMARY: We present a case of a 12-year-old boy diagnosed with ALK+LBCL. The patient had a 2-mo medical history of a calvarial mass, extensive systemic involvement, and positive bone marrow clathrin heavy chain (CLTC)-ALK fusion gene. Complete remission 1 (CR1) was achieved using the modified LMB89 Group C regimen followed by autologous stem cell transplantation. The patient relapsed 3 mo later. He then achieved CR2 with three short courses of chemotherapy (COP, reduced-dose ICE, low-dose Ara-c+VP16) and continuous alectinib targeted therapy. Afterward, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. At 16 mo after the allo-HSCT, the patient was still in CR2. CONCLUSION: The modified LMB89 Group C regimen and ALK inhibitors are effective. Allo-HSCT should be performed after remission.

Outcome of L-DEP regimen for treatment of pediatric chronic active Epstein-Barr virus infection.

PURPOSE: We intended to investigate the clinical features of paediatric patients with chronic active Epstein-Barr virus infection (CAEBV) and to examine the effectiveness of the L-DEP regimen before haematopoietic stem cell transplantation (HSCT). METHODS: A retrospective analysis was performed on 35 patients with CAEBV at Beijing Children's Hospital from January 2016 to January 2020. The efficacy and adverse events of the L-DEP regimen were evaluated. RESULTS: The median age of the 35 patients was 7.0 years old (range 2.5-17.5 years). Twenty-eight patients achieved a clinical response (80.0%, 22 in clinical CR, 6 in clinical PR) after L-DEP. In terms of virological response, 7 patients (20%) were assessed as having virological CR, and 23 patients (65.7%) had virological PR. Finally, 29 patients underwent allo-HSCT. The median survival time was 18 months (2-50 months). The 3-year overall survival rates in patients treated with chemotherapy only (n = 6) and chemotherapy followed by HSCT (n = 25) were 33.3% and 75.4%, respectively. After L-DEP 1st treatment and L-DEP 2nd treatment, the EBV-DNA loads in blood and plasma were significantly reduced compared with those before chemotherapy (median: 4.29 × 105 copies/ml vs. 1.84 × 106 copies/ml, Mann-Whitney U: P = 0.0004; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, Mann-Whitney U; P = 0.003; 2.27 × 105 copies/ml vs. 1.84 × 106 copies/ml, P = 0.0001; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, P = 0.003). Compared with the liver and spleen size before chemotherapy, the size of the liver and spleen shrank significantly after L-DEP 2nd (median 3.8 cm vs. 1.9 cm, P = 0.003; 3.8 cm vs. 0 cm, P < 0.008). In addition, after L-DEP treatment, there was no difference in the clinical or virological response rate regardless of HLH status (clinical response: 77.3% vs. 84.6%, P = 0.689; virological response: 90.9% vs. 76.9%, P = 0.337). CONCLUSION: The L-DEP regimen is an effective therapy in CAEBV for bridging to allo-HSCT.

Characteristics of Central Nervous System (CNS) Involvement in Children With Non-Hodgkin's Lymphoma (NHL) and the Diagnostic Value of CSF Flow Cytometry in CNS Positive Disease.

OBJECTIVE: To investigate the characteristics of central nervous system (CNS) involvement in children with non-Hodgkin's lymphoma (NHL) and the value of flow cytometry (FC) in the diagnosis of CNS disease in pediatric NHL. METHODS: The data of 56 newly diagnosed pediatric NHL patients with CNS involvement (CNS+/mass, CNS+/palsy, CNS+/CSF) were analyzed. The proportions and formats of CNS disease in different pathological types were compared. In addition, FC and conventional cytology (CC) of cerebrospinal fluid (CSF) were carried out in 383 newly diagnosed NHL cases. RESULTS: A total of 383 children with NHL were enrolled. Among these patients, 56 (14.6%) were diagnosed with positive CNS involvement (CNS+), 33 had bulky disease (tumor diameter >10 cm), 32 had bone marrow invasion, 32 had lactate dehydrogenase levels >1000 U/L, and 25 had invasion of more than 4 organs at the time of diagnosis. There were 14 patients with T lymphoblastic lymphoma (T-LBL), 9 with B lymphoblastic lymphoma (B-LBL), 26 with Burkitt's lymphoma (BL), and 2 with Epstein-Barr virus-positive diffuse large B cell lymphoma (EBV + DLBCL). Among the 56 CNS+ patients, 35 were CSF-positive (CSF+); there were 2 patients who were CSF+ via CC detection and 35 who were CSF+ via FC detection. The difference between CC and FC was statistically significant (P < 0.01). In the T-LBL group, 14 patients were CNS+/CSF, and in the B-LBL group, 8 were CNS+/mass. In the BL group, 22 patients were CNS+/mass and 15 were CNS+/CSF. In the anaplastic large-cell lymphoma group, 5 patients were CNS+/mass. Nine of the 56 CNS+ patients had events. The 2-year overall survival rate was 87% ± 0.046%, and the 2-year event-free survival rate was 76.2% ± 0.07%. CONCLUSION: CNS+ diagnoses were more common in pediatric NHL patients with bulky disease and/or bone marrow involvement and/or involvement of more than 4 organs at the time of diagnosis, and they were also common in the EBV + DLBCL and BL groups. FC of CSF showed important clinical significance in the diagnosis of CNS disease in pediatric NHL patients, and it can be used to significantly improve the CNS+ detection rate.