Journal of Clinical Pediatrics

Relationship between intestinal microbiota and graft-versus-host disease in allogeneic stem cell transplantation and its perspectives

WU Xiaoyan, ZHANG Wenzhi, PENG Yun

Journal of Clinical Pediatrics. 2023, 41(3): 161-166. doi:10.12372/jcp.2023.23e0061

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a strategy for the treatment of hematologic malignancies. Despite the tremendous progress in this field in recent years, there is still a high risk of post-transplant mortality. In addition to potential malignancy recurrence, the main factor contributing to this high mortality is graft-versus-host disease (GVHD). Current studies demonstrate that intestinal microbiota plays an important role in maintaining intestinal and systemic immune function, and that intestinal microbiota diversity and its metabolites can directly or indirectly influence the development of GVHD. GVHD can also damage intestinal stem cells subsequently causing intestinal flora dysbiosis. This article provides an overview of our current research on the relationship between intestinal microbiota and GVHD after allo-HSCT and summarizes current treatments for GVHD based on intestinal microbiota.

Prevention and treatment of relapse after hematopoietic stem cell transplantation in children with acute myeloid leukemia

ZHAO Mingyi, LI Jiahua, JIANG Hua

Journal of Clinical Pediatrics. 2023, 41(3): 167-174. doi:10.12372/jcp.2022.22e1591

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Acute myeloid leukemia accounts for about 15%-20% of childhood leukemia, and nearly 40% of pediatric patients still relapse after standard chemotherapy. Allogeneic hematopoietic stem cell transplantation is a powerful means to prevent its recurrence. However, some patients still relapse, and the 2-year survival rate of these patients is less than 20%. Some patients with relapse cannot tolerate or are insensitive to conventional chemotherapy. Recurrence is the main cause of death after transplantation. The prevention of relapse after transplantation ought to start before transplantation, optimize each part of the transplantation chain, and strictly follow the follow-up monitoring. In recent years, new molecular targeted drugs, new immunotherapy and CRISPR genome-edited hematopoietic stem cell therapy have also provided more treatment strategies for pediatric patients with AML relapse after transplantation. According to the procedure of transplantation chain, this paper summarized the preventive measures of each link and the treatment options of post-transplantation recurrence, in order to provide the direction and strategy for the clinic.

Research progress in complications related to hematopoietic stem cell transplantation in children with aplastic anemia

XU Jiawei, JIN Runming

Journal of Clinical Pediatrics. 2023, 41(3): 175-180. doi:10.12372/jcp.2022.22e1706

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Aplastic anemia (AA) is a bone marrow hematopoietic failure disorder that is characterized by low bone marrow hematopoiesis, complete blood cytopenia and anemia/hemorrhage/infection syndrome. Allogeneic hematopoietic stem cell transplantation is currently an important method in the treatment of severe AA. The occurrence and management of transplant-related complications remain a great clinical challenge, and their prevention and treatment can directly affect the outcome of transplantation, long-term survival and quality of life of the children. In this paper, we review the diagnosis, prevention and treatment of common transplant complications during HSCT in children with AA, with the aim of improving the success rate and survival rate of these transplanted children.

Advance in lysosomal storage disorders treated with allogeneic hematopoietic stem cell transplantation

FANG Yongjun, WEI Yuting, XUE Yao

Journal of Clinical Pediatrics. 2023, 41(3): 181-186. doi:10.12372/jcp.2022.22e1691

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Lysosomal storage disorders (LSD) are caused by structural or functional abnormalities of lysosomes resulting in defective hydrolases, causing failure to degrade the corresponding substrates, which leads to abnormal multi-organ and multi-system function. There are a variety of LSD, the clinical manifestations are not characteristic and overall prognosis are poor. The current available treatment methods include enzyme replacement therapy, gene therapy and allogeneic hematopoietic stem cell transplantation. Allo-HSCT is currently an effective modality for the treatment of pediatric patients with LSD, especially unrelated cord blood, which is the optimal graft source for the treatment of LSD. The younger the age of transplantation, the greater the benefit. Therefore, early transplantation at a definite diagnosis is emphasized and recommend before the onset of obvious symptoms. Most of the domestic institution choose the myeloablative conditioning as the conditioning regimen.

Clinical analysis of 86 csses of hematopoietic stem cell transplantation in children

WANG Wenpeng, GAO Jizhao, GUO Lei, LI Yan, LU Lihui, CHANG Ying

Journal of Clinical Pediatrics. 2023, 41(3): 187-191. doi:10.12372/jcp.2023.22e0047

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Objective To analyze the clinical efficacy of hematopoietic stem cell transplantation (HSCT) in the treatment of hematological neoplastic diseases in children. Methods The clinical data of 86 children with hematological neoplastic diseases who underwent HSCT in the Affiliated Hospital of Xuzhou Medical University from March 2016 to August 2020 were retrospectively analyzed. Results Eighty-six children (50 boys and 36 girls) with HSCT were included, and the median age was 11 (9-14) years. There were 27 cases of acute lymphoblastic leukemia (ALL), 28 cases of acute myeloid leukemia (AML), 16 cases of aplastic anemia (AA), 5 cases of lymphoma, 4 cases of chronic myeloid leukemia (CML), 3 cases of myelodysplastic syndrome (MDS), 1 case of neuroblastoma (NB), 1 case of systemic neosclerosis (SSC) and 1 case of adrenoleukodystrophy (ALD). There were 7 cases of autologous transplantation, 4 cases of umbilical cord blood transplantation and 75 cases of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time of 86 patients was 29.5 (17.6-44.0) months. A total of 84 patients were successfully implanted, and 1 patient failed autologous transplantation and 1 failed allo-HSCT. Fourteen patients relapsed, including 4 patients with autologous transplantation and 10 patients with allo-HSCT. Six patients developed grade Ⅲ/Ⅳ GVHD, all of whom were allo-HSCT. Twenty patients died, including 4 patients with autologous transplantation and 16 patients with allo-HSCT. Fisher's exact test showed that there was significant difference in the occurrence of grade Ⅰ/ⅡGVHD among the four groups of autologous transplantation, cord blood transplantation, SIB homozygous and half homozygous (P<0.001). Conclusions HSCT is an effective method to treat a variety of malignant diseases in children, but recurrence and severe GVHD after transplantation are important factors affecting the prognosis. Preventing recurrence and controlling rejection are very important in children's HSCT.

Clinical characteristics of intestinal thrombotic microangiopathosis associated with allogeneic hematopoietic stem cell transplantation in children

CHEN Yanfei, ZHONG Xuemei, MA Xin, LIAO Weiwei, LIU Rong, ZOU Jizhen

Journal of Clinical Pediatrics. 2023, 41(3): 192-196. doi:10.12372/jcp.2023.21e1226

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Objective To explore the clinicopathological features and treatment of intestinal thrombotic microangiopathopathy (iTMA) associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, and to provide reference for the early diagnosis and treatment of iTMA. Methods The clinical data of 3 children with iTMA after allo-HSCT treatment were retrospectively analyzed. Results All three patients developed gastrointestinal symptoms such as abdominal pain, intractable diarrhea or severe hematochezia 20 to 50 days after allo-HSCT. Gastroscopy showed different degrees of mucosal bleeding. Colonoscopy showed active or old bleeding, brittle mucous membrane and some erosion. Pathological examination revealed different degrees of mucosal lamina propria disappearance, atypical hyperplasia or absence of glands, and microthrombosis. Virus inclusion bodies were seen in 1 child. Combined with clinical symptoms, iTMA was considered in all the children. After the withdrawal of calcineurin inhibitor and symptomatic treatment, the symptoms of 2 children were relieved in about 2 weeks. After 20 days of stopping the use of calcineurin inhibitors and adding mycophenolate combined with methylprednisolone, plasma exchange, and deinoside, the clinical symptoms of one patient gradually improved. Conclusions iTMA is a complication of allo-HSCT in children and may be associated with graft-versus-host disease (GVHD) and cytomegalovirus infection. For children with severe refractory diarrhea after allo-HSCT, the differential diagnosis of iTMA, GVHD and cytomegalovirus infection should be made by gastrointestinal endoscopy and biopsy pathology as soon as possible, so as to help clinical timely modification of treatment strategies.

Hematopoietic stem cell transplantation for systemic mastocytosis associated with acute myeloid leukemia in children: a clinical follow-up of 2 cases

MAI Yumiao, WANG Yingjie, SUN Pan, CHEN Zhiwei, REN Bing, WANG Yingchao, LIU Yufeng, LIU Jian

Journal of Clinical Pediatrics. 2023, 41(3): 197-203. doi:10.12372/jcp.2023.22e0771

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Objective To investigate the efficacy and the clinical follow-up of hematopoietic stem cell transplantation (HSCT) for systemic mastocytosis associated with acute myeloid leukemia (SM-AML) in children. Methods The clinical data and follow-up results of 2 children with SM-AML treated by HSCT were retrospectively analyzed, and the related literature was reviewed. Results There were 2 children (1 boy and 1 girl) with SM-AML, aged from 2 to 9 years. The onset symptom of 2 cases was fever with abnormal blood image, and bone marrow smear cytology showed increased myeloblasts and spindle or atypical mastocytosis. The karyotype of t(8;21)(q22;q22) and AML1-ETO fusion gene was positive. The variation of KIT V560D (exon 11) was found in one child, and the variation of KIT T418_D419del (exon 8), KIT N822K (exon 17), and NRAS G13D (exon 2) were found in another child. After diagnosis of SM-AML, induction chemotherapy and consolidation chemotherapy were given according to CCLG-AML 2019 regimen. Bone marrow smear morphology after chemotherapy showed complete remission of AML and increased mast cells (6.6%-27.6%). One patient was treated with HSCT from HLA-mismatched unrelated umbilical cord blood donor (9/10), and the pretreatment regimen was fludarabine + busulfan (Bu) + cyclophosphamide (CTX). One patient was treated with HSCT from HLA-mismatched sibling donor (9/10, elder sister donor), and the pretreatment regimen was cytarabine + Bu + CTX+ fotemustine + antithymocyte globulin. The number of returned nuclear cells was 7.69×10⁸/kg and the number of returned CD34⁺ cells was 1.31×10⁵/kg in one patient. The number of mononuclear cells was 9.08×10⁸/kg and the number of returned CD34⁺ cells was 6.81×10⁶/kg in another patient. Hematopoietic function was reconstructed in 2 children with SM-AML. The time of neutrophils engraftment and platelet engraftment after transplantation were 11-27 d and 13-47 d, respectively. Two patients were followed up until August 2022, and they both survived. Mast cells and AML1-ETO fusion gene turned negative in one patient. Mast cells persisted in another patient, and the AML1-ETO fusion gene was still positive. Conclusions HSCT is feasible for the treatment of SM-AML. The regimen of chemotherapy before transplantation and the key problems of transplantation are worthy of further study.

Clinical analysis of treatment failure in children with acute lymphoblastic leukemia

XUE Yujuan, LU Aidong, WANG Yu, JIA Yueping, ZUO Yingxi, ZHANG Leping

Journal of Clinical Pediatrics. 2023, 41(3): 204-209. doi:10.12372/jcp.2023.22e0067

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Objective To explore the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL). Methods The clinical data of 124 newly diagnosed ALL children with treatment failure admitted from January 2013 to December 2017 were retrospective analyzed. The association of different clinical features with recurrence time and sites was compared and the possible risk factors for treatment failure was analyzed. Results By April 15, 2020, the median follow-up time was 24.0 (14.0-43.5) months. Among the 124 children who failed treatment, 82 were boys and 42 were girls. The median age at first diagnosis was 8.0 (3.3-13.0) years. The reasons for treatment failure included recurrence (104 cases), non-recurrent death (19 cases) and secondary tumor (1 case). Totally 104 ALL children relapsed, whose median recurrence time was 17.7 (3.0-57.2) months. Very early recurrence (52 cases) was the commonest recurrence time, and bone marrow (84 cases) was the commonest recurrence site. The recurrence time was correlated with initial white blood cell count, immunophenotyping, different fusion genes and risk stratifications (P<0.05). The recurrence site was correlated with initial white blood cell count and immunophenotyping (P<0.05). MRD level on day 33 was an independent risk factor for treatment failure survival rate (TFS) and overall survival (OS) rate (P<0.05). Conclusions Recurrence is the main cause of treatment failure in children with ALL. Close monitoring of early treatment response, active prevention and treatment of very early recurrence can reduce the incidence of treatment failure and improve the OS rate of children with ALL.

Clinicopathological characteristics of H3 K27-altered diffuse midline gliomas: an analysis of 95 pediatric cases

ZHOU Qi, WANG Jia, LI Jinhua

Journal of Clinical Pediatrics. 2023, 41(3): 210-214. doi:10.12372/jcp.2023.22e0347

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Objective To investigate the clinicopathological characteristics of pediatric H3 K27-altered diffuse midline gliomas (DMG). Methods The clinical and pathological data of children first diagnosed with H3 K27-altered DMG from September 2016 to July 2021 were retrospectively analyzed. Results A total of 95 patients (54 boys and 41 girls) were included, and the median age was 6.0 (5.0-9.0) years. Brainstem was the predilection site (82.1%). WHO histological grade 1-4 tumors were found in all cases and high-grade gliomas were found in most cases (65.3%). Immunohistochemical detection showed that H3 K27M (the 27th lysine of histone H3 changed to methionine) was positively expressed in all cases, and H3 K27Me3 (the trimethylation of the 27th lysine of histone H3) was decreased in 89.0% of the children. Mutant p53 (P53) was expressed in 55.6% of the children. The expression rate of isocitrate dehydrogenase 1 (IDH1) and loss expression rate of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) were low (8.5% and 18.6%, respectively). V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) was positive in only 1 case (1.2%). Molecular tests showed that O-6-methylguanine-DNA methyltransferase (MGMT) methylation was detected in 8 cases (47.1%, 8/17), and BRAF variation was detected in 1 case (2.1%, 1/48). Conclusions The commonest location of H3 K27-altered DMG children is the brainstem, and the histological grade is mostly high. ATRX loss in pediatric cases is less common and had no relationship with the tumor location.

A cross-sectional study of hyperactive behavior comorbidity allergic diseases in pre-school children

DING Xiaoyuan, ZHANG Yue, ZHANG Lishan, ZHANG Lei, YU Xiaodan

Journal of Clinical Pediatrics. 2023, 41(3): 215-218. doi:10.12372/jcp.2023.22e0468

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Objective To investigate the comorbidity and epidemiological characteristics of hyperactive behavior and allergic diseases in pre-school children in three communities of Pudong New Area in Shanghai. Methods A total of 1412 questionnaires were distributed to the parents of children in eight kindergartens from 4 to 7 years old in three communities from April to June 2021. The allergic disease screening questionnaire was mainly reported by parents and the contents were as follows: wheezing, continuous cough >1 month, asthma, eczema, allergic rhinitis, and a history of food allergies and immediate family allergies. Conners Parent Symptom Questionnaire was used to assess the children's hyperactive behavior. Results A total of 1302 valid questionnaires were received in this survey. The age of the children was (5.3±0.8) years, including 655 boys (50.3%) and 647 girls (49.7%). The rate of hyperactivity was 13.4%, the positive rate of asthma was 5.1%, and the positive rate of allergic rhinitis was 34.8% in preschool children. In pre-school children with hyperactive behavior, 10.9% had comorbidities of asthma and 59.4% had comorbidities of allergic rhinitis. Binary logistic regression analysis showed that male and allergic rhinitis were independent risk factors for hyperactive behavior in pre-school children (P<0.05). Conclusions The prevalence of hyperactive behavior comorbidity allergic diseases in pre-school children is high. Male and allergic rhinitis increase the risk of hyperactive behavior in pre-school children.

Clinical follow-up study of cognitive impairment in children with anti-N-methyl-D-aspartate receptor encephalitis

WU Wenxiao, WU Wenlin, LI Xiaojing, HOU Chi, ZENG Yiru, PENG Bingwei, ZHU Haixia, TIAN Yang, ZHAO Yuan, CHEN Wenxiong

Journal of Clinical Pediatrics. 2023, 41(3): 219-223. doi:10.12372/jcp.2023.22e0280

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Objective To evaluate and follow-up the cognitive function during convalescence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children in southern China. Methods The clinical data of children with anti-NMDAR encephalitis diagnosed and treated from 2016 to 2021 were retrospectively analyzed. According to the modified Rankin Scale (mRS Score) in the acute stage, the patients were divided into the severe group (mRS>3) and the non-severe group (mRS≤3). The results of Wechsler intelligence scale at the acute stage discharged from hospital and last follow-up were collected and analyzed. Results A total of 33 children (15 boys and 18 girls) were included in the analysis. The age of first onset was 6.0 (5.0~9.0) years. The clinical features in the acute stage were mainly convulsion (n=31), psycho behavioral symptoms (n=28), and movement disorder (n=28). The time from discharge to the last follow-up was 12.0 (4.0-33.0) months. At the last follow-up, the mRS Score was 0.0 (0.0~0.0), the full-scale intelligence quotient (FSIQ) was 82.4±12.1, the verbal comprehension index (VCI) was 85.6±16.7, the working memory index (WMI) was 84.7±13.5, and the processing speed index (PSI) was 83.5±11.0. The FSIQ and subtests scores of the children were lower than the normal level. No statistically significant differences was found in FSIQ and subtests between the severe group and the non-severe group (P>0.05) at the last follow-up. Ten children received two Wechsler intelligence tests. The time of the first test was 3.0 (1.0-5.7) months after the discharge of the first onset, and the time of the second test was 21.0 (15.5-28.0) months after the discharge of the first onset. FSIQ and VCI of the second test were higher than those of the first test, and the difference was statistically significant (P<0.05). Conclusions Children with anti-NMDAR encephalitis have cognitive impairment in the convalescence period. It is recommended to conduct regular intelligence assessment and timely reasonable intervention.

Research progress on environmental factors and congenital heart disease

RUAN Xuehua, SUN Jing, SUN Kun

Journal of Clinical Pediatrics. 2023, 41(3): 229-234. doi:10.12372/jcp.2023.22e0943

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Congenital heart disease (CHD) is a common birth defect, and its incidence is on the rise in China. At present, congenital heart disease is generally believed to be the result of the combined effect of genetic factors and environmental factors, but the specific etiology and pathogenesis are still not clear. More and more studies focus on the impact of parental environmental exposure before and during pregnancy on congenital heart disease. This article summarizes the environmental factors related to CHD in recent years, summarizes the potential influencing mechanism, and provides reference for preventing and controlling the occurrence of CHD.

Long-term management of epilepsy in children

ZHU Dengna, NIU Guohui

Journal of Clinical Pediatrics. 2023, 41(3): 235-240. doi:10.12372/jcp.2023.22e0020

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The high incidence of epilepsy in children seriously affects the quality of life of children and their families. The treatment of epilepsy is characterized by long course of treatment and many influencing factors, so long-term management is very important for improving prognosis and quality of life. There is a big gap in the management level of children epilepsy in different areas of China, which needs to be further standardized. This article introduces the long-term management of epilepsy in children.

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