Early chemotherapy response to neuroblastoma with N-myc amplification in children

Abstract

Objective To summarize the clinical features of neuroblastoma (NB) with N-myc gene amplification in order to analyze tumor shrinkage and bone marrow remission in the early stage of chemotherapy, and to eva-luate the children′s initial sensitivity to chemotherapy. Methods The medical records of 38 patients with N-myc amplification of NB were reviewed (bone marrow or tumor tissues were positive during fluorescence in situ hybridization probe), who were treated between February 2012 to December 2016 at the Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University.The regimens included chemotherapy, surgery, stem cell transplantation, radiotherapy, and maintenance treatment.The data were reviewed for the medical history.The variations of biomarker, bone marrow cells and the primary site were analyzed before and after 2 courses of CAV (Cyclophosphamide+ Adriamycin+ Vincristine)regimen chemotherapy, in order to observe the short-term effect of chemotherapy and the results were described with statistics. Results Total 38 cases were studied, 22 boys(58.9%) and 16 girls(42.1%). The median age was 30 months.The primary sites of 37 cases of tumor were located in the retroperitoneal and adrenal area, 1 case located in the posterior mediastinum.Bone marrow cytology was negative in 12 cases of them, but bone marrow biopsy suggested bone marrow metastasis, while bone marrow cytomorpholigic examinations were positive in the other 26 cases.Of all the 37 cases the lactate dehydrogenase (LDH) levels were reported higher than the normal value.LDH level was under 500 U/L in one case, 9 cases above 4 000 U/L.The neuron specific enolase (NSE) level of all the cases was higher than the normal and NSE level in 36 cases was higher than 100 μg/L.In one patient the diameter of tumor was less than 5 cm, lager than 10 cm in 32 cases.The lesion of 33 tumor cases before chemotherapy by enhanced CT was ≤100 cm3 in 12 cases, >100-500 cm3 in 11 cases, among which 6 cases ranged from 500-1 000 cm3, 4 cases larger than 1 000 cm3.All the 38 cases received 2 courses of chemotherapy.LDH levels of 4 cases became normal, and LDH levels fell under 500 U/L in 18 cases, while LDH levels of the other 3 cases were above 1 000 U/L. Among 38 cases, the NSE level in 6 cases was reduced to normal, and 16 cases reduced to 25-100 μg/L.The bone marrow examination of 36 cases reversed to negative.According to the image examination, the overall response rate after 2 courses of chemotherapy was 84.8%.One case achieved very good partial remission, 21 cases achieved partial response, 7 cases achieved metastatic remission, 2 cases had no remission, while 2 cases showed progression. After 2 courses of chemotherapy, the tumor diameter in 7 cases was less than 5 cm, while that of 22 cases was above 10 cm. Conclusions The majority primary site of NB with N-myc gene amplification is located in retroperitoneal and adrenal area.Patients with the huge tumor have a heavy burden and the biomarker is always high at the early stage.NB with N-myc gene amplification is sensitive to chemotherapy.After 2 courses of chemotherapy, there is a sharp decrease in the level of biomarker and the tumor burden.Chemotherapy can diminish the burden of tumor in early stage.But because of the huge burden and the huge size of tumor, it′s not the best time for surgery and stem cell collection.The patients should go on receiving chemotherapy for remission of disease. Key words: Neuroblastoma; N-myc gene amplification; Early response to chemotherapy