Clinical features of children with Cunninghamella spp. infection: a case report and literature review / 南方医科大学学报

We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.

Clinical and genetic analyses of juvenile myelomonocytic leukemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical and genetic features of juvenile myelomonocytic leukemia (JMML) and the association between genotype and prognosis. Methods The clinical data of 15 children who were diagnosed with JMML were collected. Next-generation sequencing was used to detect common gene mutations of JMML.@*RESULTS@#The male/female ratio was 6.5:1, and the age of onset was 19 months (range 2-67 months). Of the 15 children, 11 (73%) experienced disease onset before the age of 4 years, with abdominal distension and pyrexia as initial symptoms. All children had hepatosplenomegaly and superficial lymphadenectasis, with a number of peripheral blood mononuclear cells of >1.0×10/L and a percentage of juvenile cells of 1%-7% in peripheral blood smear. The percentage of bone marrow blasts + juvenile cells was <20%, and the percentage of monoblasts + promonocytes was 1%-10%. Of the 15 children, 10 (67%) had a higher level of hemoglobin F than the normal level at the corresponding age, with the highest level of 62.5%. All 15 children had the absence of Philadelphia chromosome, and one child had chromosome 7 deletion. All 15 children had a negative result of BCR/ABL fusion gene detection. PTPN11 gene mutation was found in 5 children (33%), NF1 mutation in 4 children (27%), CBL mutation in 3 children (20%), and RAS mutation in 3 children (20%). No children received regular chemotherapy, and one child underwent hematopoietic stem cell transplantation. The median follow-up time of 15 children was 18 months (range 1-48 months). Among the 15 children, 8 died (among whom 4 had PTPN11 gene mutation, 3 had NF1 mutation, and 1 had RAS mutation) and 7 survived. The children with PTPN11 mutation had the worst prognosis and the highest mortality rate, and those with CBL or NRAS mutation had a relatively good prognosis. The level of hemoglobin F was negatively correlated with survival time (r=-7.21, P=0.002).@*CONCLUSIONS@#In children with JMML, the type of gene mutation is associated with prognosis. The children with PTPN11 mutation often have a poor prognosis, and those with CBL or NRAS mutation have a relatively good prognosis.

Expression of CREB/Bcl-2 in bone marrow mononuclear cells of children with acute leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression and role of cyclic-AMP response binding protein (CREB) and Bcl-2 in children with acute leukemia.</p><p><b>METHODS</b>Ninety-two children with acute leukemia (leukemia group) and 30 children with non-hematologic malignancies (control group) were enrolled. The mRNA and protein expression of CREB and Bcl-2 in bone marrow mononuclear cells were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot.</p><p><b>RESULTS</b>The mRNA and protein expression of CREB and Bcl-2 in the leukemia group was significantly higher than that in the control group (p<0.01). There were no significant differences in the expression of CREB and Bcl-2 between acute lymphoblastic leukemia and acute myeloid leukemia subgroups. At the initial diagnosis, the mRNA and protein expression of CREB and Bcl-2 in children with extramedullary infiltration was higher than that in children without (p<0.05). In the leukemia group, the mRNA and protein expression of CREB and Bcl-2 in the complete remission subgroup was significantly lower than that in the non-complete remission subgroup (p<0.01). High mRNA expression of CREB and Bcl-2 in the leukemia group was positively correlated with peripheral blood leucocyte counts (r=0.62, 0.71 respectively, p<0.05). There was a positive correlation between mRNA and protein expression of CREB and Bcl-2 (r=0.75, 0.68 respectively; p<0.05).</p><p><b>CONCLUSIONS</b>The expression of CREB and Bcl-2 may be correlated with the pathogenesis and clinical prognosis of childhood leukemia, however, their expression may not be associated with the classification of acute leukemia.</p>

Therapy of Acute Lymphoblastic Leukemia Complicating Acute Respiratory Distress Syndrome in Children / 实用儿科临床杂志

Objective To approach therapy of acute lymphoblastic leukemia(ALL) complicating acute respiratory distress syndrome (ARDS) in children.Methods The therapy of seven children diagnosed as ALL complicating ARDS was analyzed, who were treated by anti-infection, methyllprednisolone, ambroxol and constant positive airway pressure (CPAP) assisted ventilation.Results Six cases were recovery and one was death. The cure rate was 85.7%. Conclusion The cure rate is high, when employing combined therapy to treat ALL complicating ARDS.

Therapeutic Alliance of Immunodepressants Treating Childhood Acute Aplastic Anemia / 实用儿科临床杂志

Objective To explore the effective method of treating childhood acute aplastic anemia(AAA) by overviewing the curative effect of therapeutic alliance to the children diagnosed as AAA with immunodepressants.Methods Retrospective analysis was performed on 13 patients diagnosed as AAA,who were treated by high dose of methyllprednisolone,antilymphocyte globulin,ciclosporin A,large dose of gamma globulin,granulocyte colony-stimulating factor and blood transfusion in 4 years.Results Among 13 cases,9 cases were healing well on the whole,one was relieved,one was improving,two were ineffective(one of them was dead).In 9 cases who were healing,WBC took(24.60?8.86) days to reach 4?10~9/L,hematoglobin took(152.22?68.88) days to reach normal and platelet took(125.55?55.86) days to reach 80?10~9/L.During the procedure of treating,infection appeared in 7 cases,the ALT and AST was high in 2 cases,hypoproteinemia and edema in 1 case,gross hematuria in 2 cases,gingival hyperplasia obviously and dedentition in 1 case.Conclusion Therapeutic alliance with immunodepressants to childhood AAA is a safe and effective method.

Study on Effects of Dibutylphthalate on Apoptosis of HL-60 Leukemic Cells and Its Mechanisms / 实用儿科临床杂志

Objective To investigate the effects of dibutylphthalate (DBP) on the proliferation and apoptosis of HL-60 leukemic cells and to study its mechanism to purge leukemic cells.Methods The effects of DBP on proliferation of HL-60 leukemic cells were measured by cell culture method. The effects on apoptosis were measured by the percentage of the apoptotic cells in morphology and of the DNA fragmentation and by DNA gel electrophoresis. The intracellular free Ca~(2+) concentration ([Ca~(2+)]i) of leukemic cells were measured by Fura-2AM method. The protein expressions of c-myc and bcl-2 genes of leukemic cells were measured by immunohistochemical assay.Results DBP could suppress the proliferation of HL-60 leukemic cells in a dose-dependent and time-dependent manner and induce them to die via apoptosis.It could elicit a intracellular Ca~(2+) redistribution and a potent extracellular calcium influx. It also down-regulated the protein expressions of c-myc and bcl-2 genes of HL-60 leukemic cells.Conclusion DBP can purge (HL-60) leukemic cells in vitro by increasing [Ca~(2+)]i of cells to initiate apoptosis and down-regulating bcl-2 and c-myc proto-gene expressions to promote cell apoptosis.

Observation of Clinical Side Effects of High-Dose-Methotrexate in Treating Children with Acute Lymphoblastic Leukemia / 实用儿科临床杂志

1.0 mmol/L).The clinical side effects after medication circa were compared between two groups.Results There was no significant difference in myelosuppression,liver functional lesion,gastrointestinal tract reaction and infection in 2 groups.But following the increase of MTX blood drug level,the incidence rate of skin mucosa contamination,electrocardiographic abnormality,the cardiac creatase abnormity and nervous system symptoms significantly increased.Conclusions In the course of child ALL treatment with HD-MTX+CF,the side effects are common and individual difference is obvious.Specific treatment on individuals is suggested.J Appl Clin Pediatr,2006,21(3):170-171