Feasibility study on the control of clonic symptoms in children with neuroblastoma based on systemic chemotherapy combined with high-dose of immunoglobulin and prednisone / 中华实用儿科临床杂志

ABSTRACT

Objective To explore the feasibility of immunotherapy intermittently with high dose intravenous immunoglobulin(HD-IVIG)impact therapy combined with prednisone on the basis of systematic chemotherapy to control the clonic symptoms of children with neuroblastoma(NB).Methods A retrospective analysis was made based on the clinical data of 8 NB children with combined clonus,who were admitted in Beijing Children's Hospital,Capital Medical University from May 2011 to February 2017.And analysis and summary were also made according to patients' clinical data,neurological symptoms,therapy methods and prognosis.The follow-up visiting was ended on March 1,2017.Results Eight patients were investigated,3 male and 5 female,with onset age ranged from 10.0 to 35.5 months (the median age was 17.5 months),and the period from occurrence of clonic symptoms to a definite diagnosis and starting treatment was 1.25 to 6.50 months (the median time was 3.60 months).All patients developed kinds of neurological syndrome clinically,such as clonus on the trunk and limbs,and 5 cases of them were involved in combined opsoclonus-myoclonus syndrome (OMS).All patients went for their first-time consultancy at the Neurology Department of Beijing Children's Hospital,Capital Medical University or local hospitals.The primary tumor focus was found in unilateral adrenal gland in 2 cases,1 case in bilateral adrenal glands,2 case in retroperitoneal region,2 cases in mediastinum and 1 cases in presacral region.The image examination indicated 1 case with a tumor focus,the diameter of it more than 5 cm.Except for 1 case involved in the local invasion of tumor in vertebral body,the images examination of all other patients showed the focus in the primary location,without visible distant metastasis or no abnormality was seen by head magnetic resonance imaging (MRI) examination.Initially,four cases had normal neuronal specific enolase (NSE) and 4 had higher NSE;one case had higher urine vanillylmandelic acid (VMA) and 7 normal;3 cases had higher urine homovanillic acid(HVA) and 5 normal.Among 8 patients,the pathological pattern of 6 cases was NB,in which 4 cases were of differentiated type and 2 cases of poorly differentiated type;the pathological pattern of 2 cases was ganglion cell NB,in which 1 case was of nodular type and 1 case of mixed type.N-MYC was not amplified.Clinical staging5 cases of stage Ⅱ and 3 cases of stage Ⅲ.Clinical grouping7 cases of intermediate risk group and 1 case of low risk group.So far,1 case lost follow-up in that the child didn't receive regular diagnosis and treatment due to economic problem,so significant improvement of clonic symptoms was not seen,all other patients were given the immunotherapy with intermittent HD-IVIG impact therapy and oral administration of prednisone based on systematic chemotherapyimmunoglobulin was applied respectively before,during and after chemotherapy in multiple impact treatments;3 cases received 4 courses of treatment,2 cases received 3 courses of treatment and 2 cases received 2 courses of treatment.Prednisone was given orally during the application of immunoglobulin,from the full dose and with the course of treatment of 1.0 to 5.5 months,3 months on average;then the dose was gradually reduced.With the follow-up up to now,hormone was discontinued in 4 cases and the total course of treatment was 8 to 12 months,10 months on average.One month after the treatment of patients in 4 cases,the clonic symptoms were improved or disappeared in 5 to 12 months;the clonus of patients in 2 cases was improved respectively 3 months after treatment and half a year after drug withdrawal,in which the symptoms of 1 case disappeared completely 1 year after treatment and the slight clonic symptoms of 1 case still existed by the update follow-up.Except for 1 case of patient lost to follow-up,the regular primary tumor focus of all patients indicated that the disease conditions were in a stable state.Conclusions The immunotherapy intermittently applied with HD-IVIG impact therapy in combination with prednisone based on regular systematic chemotherapy can effectively control the clonic symptoms of children with NB.The earlier the intervene treatment for clonic symptoms is recommended,so that the faster recovery of symptoms can be achieved.Early diagnosis and early treatment play a helpful role in the recovery of children with neurological symptoms.