Optimal dosage of rituximab for children with Burkitt lymphoma.

The current chemotherapy treatments have led to an improvement in survival rates for pediatric Burkitt's lymphoma (BL). Survival in children with high-grade, mature B-cell non-Hodgkin's lymphoma (B-NHL) has been prolonged by six rituximab doses combined with chemotherapy, whereas the efficacy of four doses has not been reported. This study aimed to explore optimal therapeutic strategies-the number of doses of rituximab based on different risk groups-and also aim to investigate the clinical characteristics of Chinese pediatric BL. This study consecutively enrolled children with BL in Beijing Children's Hospital who received French-American-British mature B-cell lymphoma 96 (FAB/LMB96). The patients were divided into three groups: R0 group (chemotherapy alone), R6 group (chemotherapy combined with six rituximab doses), and R4 group (chemotherapy combined with four rituximab doses). The clinical characteristics and outcomes were evaluated. Univariate and multivariate analyses and prognostic nomogram were used to assess prognostic factors. A nomogram was developed that predicted overall survival based on the Cox proportional hazards model, and the concordance index (C-index) and a calibration curve were used to determine its predictive and discriminatory capacity. We enrolled 385 boys and 71 girls, with a median age of 6 years (1-14 years). Of these, 296 patients (65%) had initial abdominal symptoms, 182 (40%) had bulky disease, 46 (10%) had B symptoms, 77 (16.9%) had BL-ALL (blasts ≥ 25% in bone marrow (BM)), 96 (21%) had central nervous system (CNS) disease, 406 (89%) were in stages III-IV, 378 (83%) were in group C, 170 (37.2%) had lactate dehydrogenase (LDH) levels ≥ 1000 U/L at initial diagnosis, and 137 (30%) had tumor lysis syndrome. The R0, R6, and R4 groups included 79, 144, and 227 patients, respectively. Six patients were excluded due to treatment withdrawal for various reasons. The 3-year overall survival (OS) and event-free survival (EFS) percentages were 92% ± 1.3% and 91.3% ± 1.3%, respectively, in all cohorts, whereas the 3-year EFS percentage was 83.5% ± 4.2%, 93% ± 2.1%, and 92.9% ± 1.8% in the R0, R6, and R4 groups, respectively (P = 0.025). The nomogram included four important variables based on a multivariate analysis of the primary cohort: course of disease ≤ 20 days, presence of bulky disease at the beginning of diagnosis, central nervous system(CNS) invasion, and dosage of rituximab. The calibration curve showed that the nomogram was able to predict 3-year OS accurately. The C-index of the nomogram for OS prediction was 0.79 for both cohorts. In our hospital, pediatric BL was more commonly observed in school-age boys with an abdominal mass and mostly in advanced stages at initial diagnosis. The FAB/LMB96 regimen combined with rituximab significantly increased survival outcomes. We observed no significant differences between four and six doses of rituximab in terms of treatment outcomes. The proposed nomogram provides an individualized risk estimate of OS in patients with BL and may assist treatment decision-making or rituximab dose design.

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma.

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

Acute kidney injury in children with lymphoma.

OBJECTIVE: To analyze the epidemiology of acute kidney injury (AKI) in children with lymphoma and to assess the incidence, risk profile of AKI, and effects on renal function in children with lymphoma during their first 30 days of hospitalization. MATERIALS AND METHODS: This was a retrospective screen of electronic hospital and laboratory databases to select hospitalized children who were first diagnosed and treated for lymphoma at Beijing Children's Hospital between 2020 and 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. We analyzed the incidence and risk factors for AKI in children with lymphoma during their first 30 days of hospitalization. We also analyzed mortality rate and the incidence of kidney recovery over a 1-year follow-up period. RESULTS: Of the 295 children with lymphoma (which were all non-Hodgkin lymphoma), 42 (16.5%) experienced AKI events during the first their 30 days of hospitalization. The proportion of patients with lymphoma clinical stage 4 was higher in the AKI group than in the non-AKI group (66.7 vs. 43.7%, p < 0.05). Tumor lysis syndrome (TLS), lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma. Severe AKI was associated with TLS, sepsis, and a higher need for intensive care. Over 1-year of follow-up, none of the survivors developed impaired renal function or proteinuria. However, the mortality of children in the AKI group was significantly higher than that in the non-AKI group (p < 0.05). CONCLUSION: TLS, lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma during the first 30 days of hospitalization. Clinicians should increase their awareness of AKI in hospitalized patients with lymphoma.

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.

Clinical features and outcomes of bowel perforation in primary pediatric gastrointestinal lymphoma.

BACKGROUND: Whether surgery can improve the prognosis of patients with primary pediatric gastrointestinal lymphoma (PPGL) who experienced bowel perforation remains controversial. This study aimed to evaluate the prognosis of such patients. METHODS: Nine patients pathologically diagnosed with PPGL who experienced perforation at our center between January 2010 and December 2020 were enrolled and divided into two groups: those with perforation during (n = 4) and before (n = 5) chemotherapy. Their medical records were reviewed, and long-term follow-up was conducted by telephone in February 2021. RESULTS: All patients with perforation during chemotherapy were diagnosed with PPGL in the outpatient department. The mean time from outpatient visit to chemotherapy was 17.3 ± 6.1 days. Two patients experienced perforation during the first chemotherapy regimen and received conservative treatment, while the others developed perforation after multiple chemotherapy regimens and underwent surgery. All of the patients received regular chemotherapy and survived for a mean follow-up time of 3.8 ± 1.9 years. No patient with perforation before chemotherapy had a definite diagnosis in the outpatient department. Among these patients, 4 experienced perforation and underwent surgery, of whom 3 developed perforation-related complications and died; the other recurred after chemotherapy. Only the patient who received conservative treatment was diagnosed with PPGL before chemotherapy, received regular chemotherapy, and survived without a recurrence for 1.0 year. CONCLUSION: Prompt diagnosis and chemotherapy improve the prognosis of PPGL. Surgery does not affect the prognosis of patients with perforation during chemotherapy but may accelerate disease progression in patients with perforation before chemotherapy.

A case of gaucher disease with a rare complication of gaucheroma and protein-losing enteropathy.

This case report describes a patient initially diagnosed with Gaucher disease (GD) with type I with homozygous mutation c.1448T > C p. (Leu483Pro) at age of 2, presenting with hepatosplenomegaly and cytopenia. Imiglucerase replacement therapy was initiated. At age 17, bilateral hearing loss developed, with subsequent Cranial MRI revealing thalamic damage, leading to a reclassification as type 3 GD. By age of 20, the patient presented with a range of symptoms, including abdominal pain, diarrhea, hypoproteinemia, multiple lymphadenopathy, edema, and Gaucher cell infiltration in the lymph nodes. Comprehensive diagnosis identifies Gaucher tumor and protein-losing enteropathy. Imiglucerase therapy at 90-120 U/kg every 2 weeks significantly improved clinical symptoms, emphasizing the importance of tailored interventions for managing GD manifestations.

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.

[Clinical features and prognosis of children with lymphoblastic lymphoma].

OBJECTIVE: To evaluate the clinical characteristics of childhood lymphoblastic lymphoma (LBL) and therapeutic efficacy of BCH-LBL-2003 regimen modified from BFM-90 protocol. The drug-related toxicities and prognostic factors were explored at the same time. METHODS: From Janurary 2003 to December 2009, 112 newly diagnosed LBL patients at the Hematology Center of Beijing Children's Hospital were enrolled in this study. The patients were treated with modified BFM-90-LBL protocol. RESULTS: At a median follow-up of 29 months (1 to 90 months), the patients were evaluated on day 33 and at the end of induction therapy. The bone marrow complete remission (CR) rates were 96.4% and 100%, respectively. Meanwhile, the complete remission (CR) rates of tumor were 77.7% and 94.5%, and the partial remission (PR) rates were 22.3% and 5.5%, respectively. The overall response rate was 100%. The 3-year overall survival (OS) rate was 89.1% and 5-year OS was 87.0%. The 3-year event-free survival (EFS) was 85.4% and 5-year EFS was 83.3%. Eleven cases relapsed during the treatment (4 BM relapses, 3 CNS recurrences, 3 primary site and 1 lymph node of neck and BM). Eleven patients died (3 died of infection and 8 died of progressive disease after relapse). All patients experienced grade 3-4 hematological toxicity. Univariate analysis indicated that lack of CR at the end of induction therapy, immunophenotype, bulky tumor and course of disease had prognostic significance. CONCLUSIONS: Lymphoblastic lymphoma in childhood and adolescence is highly aggressive. BCH-LBL-2003 protocol is very effective. The treatment-associated side effects were tolerable. Patients who didn't get CR at the end of induction therapy, with T-cell immunophenotype, with bulky disease and the course of disease less than 30 days may have a poor prognosis.

Complete remission of Hodgkin's lymphoma in a pediatric patient with TTN gene mutation treated with brentuximab vedotin combined chemotherapy without anthracyclines: A case report.

Introduction: There is no guideline for the treatment of Hodgkin's lymphoma (HL) in pediatric patients with titin (TTN) gene mutation and heart failure. We explored the feasibility of using brentuximab vedotin (BV) plus chemotherapy without anthracyclines to treat one pediatric HL patient with TTN mutation. Case presentation: A 5-year and 7-month male patient was admitted to the hospital due to high fever and shortness of breath. He was diagnosed with stage IV IVB high-risk Hodgkin's lymphoma (lymphocyte-depleted type) at admission. Echocardiography showed that the left ventricular ejection fraction (LVEF) was 27%. The gene sequencing revealed a pathogenic variant in the TTN gene. Due to the risk of cardiotoxicity of anthracycline, he received 6 cycles of chemotherapy (no anthracyclines), 4 cycles of them plus BV with dosing 1.8 mg/kg, q3w. The tumor was reduced by 77% after 2 cycles of BV and 4 cycles of chemotherapy. At the end of 4 cycles of BV and six courses of chemotherapy, with complete remission achieved, the tumor was reduced by 85%. After 11 months of follow-up, the patient was still in complete remission with no adverse events reported, and his LVEF improved to 62%. Conclusion: The combination of BV with chemotherapy is effective and well-tolerated for pediatric HL patients with TTN gene mutation.

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.

The transcription factor TOX is involved in the regulation of T-cell exhaustion in neuroblastoma.

T-cell exhaustion is one of the key reasons for attenuated T-cell cytotoxicity against tumours. At both the expression and epigenetic levels, a number of genes, including the transcription factor TOX, are believed to be implicated in regulating T-cell exhaustion. In the present study, we found that in NB patients, the ratio of exhausted T cells, featuring upregulated PD-1 and Tim-3, was increased. Meanwhile, the expression of inhibitory surface receptors, including Lag-3, CD160, VISTA and KLRG1, was also increased, but this was accompanied by a reduced ability to release the effector molecules IL-2, IFN-γ, TNF-α and Granzyme B in CD3+ T cells from NB patients. It is noteworthy that NB-derived memory T cells (Tm) showed more obvious exhausted characteristics than other T cells. Moreover, the T cells from NB patients possessed a higher potential for exhaustion conversion upon in vitro TCR stimulation in our time-course culture experiment. In NB patients, T-cell exhaustion was demonstrated to correlate with the elevated expression of TOX in freshly sorted CD3+ T cells as well as in anti-CD3 stimulated PBMCs. Most importantly, our data supported the idea that the hypomethylation of the TOX promoter may be one of the initiators that regulates TOX expression and enables TOX to play a crucial role in T-cell exhaustion reprogramming in NB patients.

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.

Treatment outcome in children with central nervous system-positive Burkitt lymphoma using only intrathecal and systemic chemotherapy combined with rituximab.

BACKGROUND: With current chemotherapy treatment, >90% of survival has been obtained for Burkitt lymphoma (BL). In this study, the demographic characteristics and treatment outcomes are presented for 78 children in China with central nervous system-positive (CNS+) BL. METHODS: This retrospective study consecutively enrolled 78 CNS+ BL patients in Beijing Children's Hospital (BCH) from 2007 to 2019 who received the BCH B-cell non-Hodgkin's lymphoma regimen (modified by French-American-British mature lymphoma B-cell 96 [FAB/LMB96] C1 arm ± rituximab). Clinical characteristics, methods of disease detection in the CNS, and outcomes were evaluated. Univariate and multivariate analyses were used to assess prognostic factors. RESULTS: The median age of 65 boys and 13 girls at the time of diagnosis was 5.7 years (ranging from 1 to 14 years). Patients were followed up for a median time of 34 months (ranging from 1 to 72 months). Bone marrow invasion was found in 38 (48.7%) patients. There were 48 (61.5%), 44 (56.4%), and 25 (32%) patients with cranial nerve palsy, intracerebral mass (ICM), and para-meningeal extension, respectively. Abnormal cerebrospinal fluid (CSF) morphology and CSF immunophenotype appeared in 15 (19.2%) and 15 (19.2%) patients, respectively. There were 69 (88.5%) patients treated with chemotherapy combined with rituximab, and nine patients were treated solely with chemotherapy. Finally, five patients died of treatment-related infection, recurrence occurred for 13, and one developed a second tumor. The 3-year overall survival and event-free survival rates were 78.9% ±â€Š4.7% and 71.4% ±â€Š6.0%, respectively. Treatment with chemotherapy only, ICM positivity, and >4 organs involved at diagnosis were independent risk factors. CONCLUSIONS: Rituximab combined with a modified LMB96 regimen has greatly increased the efficacy of treatment for Chinese children with CNS+ BL, and with the continuous collection of outcome data, treatment-related complications are decreasing. For further verification, a large sample multicentre randomized controlled study should be performed to explore a treatment scheme for Chinese children with even greater efficacy.

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.

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.

[Clinical features of hepatitis-associated aplastic anemia in children].

OBJECTIVE: To study the clinical features of hepatitis-associated aplastic anemia (HAAA) in children. METHODS: The clinical data of the children with newly diagnosed HAAA from January 2007 to December 2008 were respectively studied, including clinical manifestations, and blood routine, bone marrow examination, viral serology and immune function results as well as treatment and prognosis. RESULTS: A total of 8 children were confirmed as HAAA, accounting for 4.9% in children with aplastic anemia. There were 7 males and 1 female. The median age was 7.5 years (range 4.4 to 10.3 years) at diagnosis. They had negative serologic results and the causes of hepatitis could not be identified. The median interval from hepatitis occurrence to blood cell reduction was 6 weeks. Three cases were diagnosed as severe aplastic anemia and 5 cases as very severe aplastic anemia. Severe T cell immune disorders were found in all 8 cases. The percentage of Ts cells increased and the percentage of Th cells decreased significantly in the 8 children with HAAA. Four children survived after immune suppress treatment, three children died within one month after diagnosis and one child required own discharge without treatment. CONCLUSIONS: HAAA is more frequent in male school children. The children with HAAA have severe T cell immune disorders, with a higher early death rate. Immune suppress treatment is effective.

Central nervous system relapse in a pediatric anaplastic large cell lymphoma patient with CLTC/ALK translocation treated with alectinib: A case report.

BACKGROUND: The aberrant expression of the anaplastic lymphoma kinase (ALK) gene in ALK-positive (ALK+) anaplastic large cell lymphoma (ALCL) is usually due to t(2;5)/NPM-ALK. However, rarely, aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes. Central nervous system (CNS) metastasis is very rare in ALK+ALCL. Patients with CNS involvement show an inferior prognosis. CASE SUMMARY: Here, we present the case of an 8-year-old girl diagnosed with ALK+ALCL. She presented with fever, skin nodules, leg swelling, and abdominal pain over the preceding 6 mo. She had extensive involvement and showed an extraordinary rare translocation, t(2;17)/CLTC-ALK, as demonstrated by RNA-seq. She underwent chemotherapy as per ALCL99, followed by vinblastine (VBL) maintenance treatment, and achieved complete remission. However, she developed CNS relapse during VBL monotherapy. The patient achieved a durable second remission with high-dose chemotherapy (including methotrexate 8 g/m2) and continuous treatment with alectinib and VBL. CONCLUSION: Alectinib showed significant and durable CNS effects in this patient. However, more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.

[An analysis of mutations causing Gaucher disease in Chinese population].

OBJECTIVE: To review and investigate the relationship of genotype and phenotype in Chinese patients with Gaucher disease (GD). METHODS: The samples were first screened for known mutations as reported previously in Chinese population. Long chain PCR and nested PCR were employed to amplify the segments of glucocerebrosidase functional gene in patients with unknown mutant alleles. The products of nested-PCR were subjected to DNA sequencing to detect the new mutations. RESULTS: Forty kinds of mutations were detected in this panel of patients. The L444P mutation was the most common one accounting for 33.0% of mutant alleles. It was followed by F213I, N188S, V375L and M416V. CONCLUSION: There are at least 40 mutations in Chinese GD patients. The spectrum of mutation is significantly different from that in Caucasians. 70% of mutant alleles have been characterized. It becomes feasible to make clinical and prenatal diagnoses through gene analysis.

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

Abstract 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.