Ci Pan

Cost of childhood acute lymphoblastic leukemia care in Shanghai, China

Acute lymphoblastic leukemia (ALL) is the most common and curable malignant pediatric disease in children. In low‐ and middle‐income countries, however, economic factors prevent many patients from receiving complete treatment, even as government and insurance entities lack complete data on the costs for ALL therapies. Here, we analyzed the overall costs for pediatric ALL therapies and their constitutive elements.

Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL). In children, T-ALL usually has a worse prognosis than B-ALL, although childhood T-ALL prognoses have improved remarkably. The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance. Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor, which confers a much poorer prognosis than any other form of T-ALL. This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Flow cytometry data from T-ALL patients enrolled in Shanghai Children’s Medical Center between July 2002 and October 2010 were assessed according to Dr. Campana’s protocol. Among total 89 T-ALL cases, 74 cases had enough immunophenotype data available to differentiate between ETP (CD1a−, CD8−, CD5dim, at least one marker of stem cell or myeloid lineage) and non-ETP. From these 74 subjects, 12 ETP-ALL cases (16.2%) were identified. The event-free survival (EFS) rate at 66.8 months was 11.1% ± 10.1% for ETP-ALL and 57.6% ± 5.6% for non-ETP-ALL (P = 0.003). The overall survival rates were 13.3% ± 11.0% for ETP-ALL and 64.7% ± 6.3% for non-ETP-ALL (P = 0.002). Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis.

Clinical outcome of children with newly diagnosed acute lymphoblastic leukemia treated in a single center in Shanghai, China

Aim of the study is to determine the clinical outcome of 158 cases of childhood acute lymphoblastic leukemia (ALL) treated with a risk-directed protocol in Shanghai, China. One hundred fifty eight consecutive newly diagnosed patients were enrolled in the ALL-XH-99 protocol. The Kaplan – Meier method was used to estimate survival rates and comparisons were made by using the 2-sided log-rank test. Of all the 158 patients evaluated, 153 (96.8%) achieved complete remission (CR) in a median time of 33 days. The 5-year event-free survival (EFS) rate was 66.9% ± 13.1%. Relapse occurred in 15 patients with isolated hematologic relapse in 13 and isolated central nervous system relapse in 2. Seven patients died of treatment-related complications. The medical cost for each patient does not exceed 25,000 USD. Contemporary risk-directed therapy can cure approximately two thirds of patients with ALL at relatively low cost. The challenge is to extend curative treatment to less privileged patients having fewer financial resources.

Minimal residual disease is a prognostic marker for neuroblastoma with bone marrow infiltration.

ObjectiveThis pilot study focused on whether flow cytometry (FCM) detection of minimal residual disease in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB). Patients and MethodsFifty-seven stage 4 NB patients with BM infiltration were enrolled in this study. All of them received NB-2001 protocol. BM samples were examined for tumor cell contamination by both morphology and FCM with CD45-FITC−/CD81-PE+/CD56-PECy5+ monoclonal antibodies cocktail at diagnosis and after 4 courses of chemotherapy. ResultsBM samples of all patients were positive at diagnosis by FCM, and samples from 30 patients became negative after 4 courses of chemotherapy, 10 patients relapsed (33.3%) in mean 45.5 months, range 7 to 69. Another 27 patients remained positive, and 20 of them relapsed (74.1%) in mean 24.2 months, range 8 to 48. There was a statistically significant difference in event-free survival between the 2 groups (P = 0.002). ConclusionsPersistence of minimal residual disease in BM may work as a chemotherapy response marker and predict the prognosis in advanced NB.

Prognostic influence of minimal residual disease detected by flow cytometry and peripheral blood stem cell transplantation by CD34+ selection in childhood advanced neuroblastoma.

To determine whether neuroblastoma (NB) minimal residual disease (MRD) in bone marrow (BM) detected by flow cytometry could predict prognosis and whether tumor cell purging by CD34+ cell selection prior to transplantation will impact on disease‐free survival.

Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001–2010

This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China.

Homoharringtonine as a backbone drug for the treatment of newly diagnosed pediatric acute myeloid leukemia: a report from a single institution in China

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in the treatment of acute myeloid leukemia (AML). The purpose of this study was to evaluate the efficacy and toxicity of HHT for de novo pediatric AML. Patients entered in this study were treated with a regimen including HHT 3.5 mg/m2 day for 9 days for 6–8 cycles after induction and consolidation with cytarabine plus daunorubicin (DA). One hundred and seventy-one eligible patients, with a median age of 7.58 years, were enrolled. Complete response was obtained in 140/171 (81.9%) cases within 60 days (2 cycles) after DA induction. The 5-year event-free survival was 52.75%. Severe myelosuppression was seen in all patients, with an average minimum WBC count of 686/μl. Following the HHT-including regimen, one patient suffered severe pancreatitis, and a second with a history of congenital hepatitis B suffered liver failure. No significant drug-induced hypotension, fluid retention, hyperglycemia, or cardiac toxicity was detected in this study. Other toxicities, including nausea, vomiting, diarrhea, and mucositis, were mild. HHT-including protocols may emerge as useful therapeutic options in future clinical trials.

Diffuse cavernous hemangioma of the spleen with Kasabach-Merritt syndrome misdiagnosed as idiopathic thrombocytopenia in a child

BackgroundMost cavernous hemangiomas in the spleen are small lesions that are found incidentally and patients usually present with no symptoms. Imaging is able to detect the lesions that are considered as diagnostic evidence. But some patients with diffuse cavernous hemangioma may present with anemia, thrombocytopenia, coagulopathy and bleeding, which might be misdiagnosed as idiopathic thrombocytopenia with disseminated intravascular coagulation (DIC). Splenectomy is the most effective therapy for diffuse cavernous hemangiomas with symptoms.MethodsThe history, imaging results, pathologic findings, diagnosis and treatment of a 34-month-old boy with severe petechiae were reviewed.ResultsThe boy was diagnosed as having refractory idiopathic thrombocytopenia (ITP) because of low platelet count and bleeding at a local hospital. He had no response to a full-dose of corticosteroid and a high-dose of immunoglobulin (2 g/kg). Huge splenomegaly and DIC were found after 7 months. Diffuse cavernous hemangioma of the spleen was highly suspected, but it was not confirmed by B ultrasound, enhanced CT or MRI. DIC and bleeding were solved by low molecular weight heparin, supplement of fibrinogen and prothrombin complex. A diffuse cavernous hemangioma involving the whole spleen was confirmed pathologically following a successful splenectomy. The boy recovered completely without any complication after the operation.ConclusionsDiffuse cavernous hemangioma of the spleen should be differentiated from ITP associated with splenomegaly. Radiological and overall physical examination should be emphasized for refractory ITP cases.

ATG-Fresenius S combined with cyclosporine a: an effective immunosuppressive therapy for children with aplastic anemia.

For the first time, we conducted a 2-center retrospective study to show the efficacy of antithymocyte globulin (ATG)-Fresenius S plus cyclosporine treatment of children with severe aplastic anemia. From March 1997 to May 2011, a total of 124 patients (median age, 7.5 y; range, 1.5 to 16 y) from 2 centers with acquired AA treated with an immunosuppressive therapy (IST) regimen, consisting of ATG-Fresenius S (5 mg/kg per day for 5 d) and cyclosporine, were enrolled. The response rate was 55.6%. The median time between IST and response was 6 (0.5 to 18) months. After a median follow-up time of 29 (6 to 153) months, the rates of relapse and clonal evolution were 3.2% and 0.8%, respectively. Overall, 17 patients (13.7%) died in this study: 14 resulted from sepsis, 1 resulted from intracranial hemorrhage, 1 occurred after hematopoietic stem cell transplantation, and 1 resulted from clonal disease progression. The 5-year overall survival rate for the entire cohort was 74.7%. IST responders had a better survival rate (100%) than nonresponders (70.7%). The use of ATG-Fresenius S plus cyclosporine as a first-line immunosuppressive treatment appeared to be effective for children with severe aplastic anemia in our study. ATG-Fresenius S could be another option in the treatment arsenal, especially in countries where the other ATG products are harder to acquire.

Results of RS-99 protocol for childhood solid tumors

BackgroundLittle was known about the therapeutic result of rhabdomyosarcomas (RMSs) and other malignant tumors until the end of the last century in China. Very few prospective clinical research results have been reported. We designed a RS-99 protocol under close cooperation of a multidisciplinary team including surgeons, radiologists, pathologists, and pediatric oncologists at Shanghai Children’s Medical Center. This study aimed to improve the prognosis of childhood solid tumors and analyze the results of different tumors with the same protocol, including RMSs, the Ewing sarcoma family of tumors (ESFTs), and ex-cranial germ cell tumors (GCTs).MethodsSixty-six patients with malignant solid tumors [RMS (n=30), GCT (n=22), and ESFT (n=14)] were enrolled on the RS-99 protocol from October 1998 to October 2006. They were 34 girls and 32 boys aged 9 to 194 months. The protocol involved surgery, radiotherapy and chemotherapy which included VCP (vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and IEV (etoposide, vincristine and ifosfamide) for the low-risk group, AVCP (adriamycin, vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and IEV for the intermediate-risk group and high-risk group. Peripheral blood stem cell transplantation was suggested for the high-risk group. Radiotherapy was only given for RMS and ESFT. Differences in survival between the groups were determined by comparison of entire survival curves and tested by the Kaplan-Meier method and the log-rank tests.ResultsThe 5-year event-free survival (EFS) for the whole group (RMS, ESFT and GCT) was 60%. The 5-year EFS for children with RMS was 35% (95% CI 16–54), GCT was 79% (95% CI 70–88) and ESFT was 72% (95% CI 58–86). The 5-year EFS showed that the patients with RMS in the retroperitoneum-pelvis did not have a better result than those with tumors in other sites (P=0.604). The histological classification of RMS exerted prognostic influence on the estimated 5-year EFS (P=0.04). Tumor stage and risk group were also contributive to prognosis (P=0.008). For GCT patients, the primary sites of tumors and their histological classification did not influence the therapeutic result (P=0.814). The 5-year EFS was 100% in stage I and II versus 62% in stage III and IV patients (P=0.02). Because of the small number of patients, we did not analyze the prognostic factors for patients with ESFT. No organ failure or functional impairment occurred in the patients enrolled in the RS-99 protocol. One ESFT patient developed a second cancer.ConclusionsThe RS-99 protocol is well tolerated and is reasonable for the 3 different tumors. Risk-based grouping protocol design is needed and the protocol for high risk RMS should be revised.