Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review.

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

HLA-DRB5 Overexpression Promotes Platelet Reduction in Immune Thrombocytopenia Mice Model by Facilitating MHC-II-Mediated Antigen Presentation.

INTRODUCTION: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development. METHODS: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8+ T-cell proportion in mice blood was detected by flow cytometry. RESULTS: HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8+ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb. CONCLUSION: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.

Tumor-suppressing effects of miR-381-3p in pediatric acute myeloid leukemia via ROCK1 downregulation.

MicroRNA (miR)-381-3p is the newly discovered tumor-associated miRNA, which is frequently associated with diverse human malignancies; but, it is still unknown about its effect on acute myeloid leukemia (AML) in children. This work focused on exploring miR-381-3p's effect on childhood AML and identifying the possible mechanisms facilitating new treatment development. Using qRT-PCR analysis, miR-381-3p expression remarkably reduced in pediatric AML patients and AML cell lines (HL-60 and U937). Following transfection of miR-381-3p mimic or inhibitor into HL-60 and U937 cells, we conducted MTT assay to evaluate cell proliferation, flow cytometry (FCM) to measured cell apoptosis and cell cycle, whereas Transwell assays to detect cell invasion and migration. Our results demonstrated that miR-381-3p overexpression remarkably repressed cell growth, invasion and migration; additionally, miR-381-3p overexpression resulted in arrest of cell cycle and enhanced cell apoptosis. In contrast, miR-381-3p knockdown led to an opposite effect. Moreover, we predicted miR-381's target gene and validated it by luciferase reporter assay and TargetScan, separately. We identified miR-381-3p's binding site in ROCK1 3'-UTR. As revealed by Western-blot (WB) assay, miR-381-3p overexpression notably suppressed ROCK1 level. Moreover, restoring ROCK1 expression abolished miR-381-3p's inhibition on cell proliferation, invasion and migration. Data in this work indicated the role of miR-381-3p as the tumor suppressor within pediatric AML by targeting ROCK1. Therefore, miR-381-3p might serve as a potential therapeutic target for the treatment of pediatric AML.

Homo sapiens circular RNA 0003602 (Hsa_circ_0003602) accelerates the tumorigenicity of acute myeloid leukemia by modulating miR-502-5p/IGF1R axis.

Acute myeloid leukemia (AML) has become a worldwide malignant cancer. We intended to investigate the critical roles and mechanism underlying homo sapiens circular RNA 0003602 (hsa_circ_0003602) in AML progression, especially in tumor cell proliferation, migration, invasion, and apoptosis. Real-time PCR was applied to identify the differential expression of hsa_circ_0003602 and miR-502-5p in AML bone marrow tissues and cell lines. In addition, western blot analysis was employed to determine the levels insulin-like growth factor 1 receptor (IGF1R) protein. The biological behaviors were assessed by CCK-8 cell viability assay, flow cytometry assay for apoptosis detection, and Transwell migration and invasion assay. The relationships between target miRNA and downstream mRNA were investigated by bioinformatics, luciferase reporter assay, and biotin-labeled RNA pull-down assay. Hsa_circ_0003602 was upregulated and predicted poor survival in AML. Knockdown of hsa_circ_0003602 in AML cell lines induced the inhibition of proliferation, migration, and invasion and caused apoptosis. Hsa_circ_0003602 sequestered miR-502-5p by functioning as a competitive endogenous RNA (ceRNA), thereby regulating IGF1R expression. Hsa_circ_0003602 acted as a tumor promoter in AML via miR-502-5p/IGF1R axis. Our study provides evidence that hsa_circ_0003602, miR-502-5p, and IGF1R might form a regulatory axis to affect the carcinogenicity of AML cells and provide potential targets for the treatment of AML.

Investigating the potential benefit of second biopsy of residual mass in pediatric mature B cell non-Hodgkin lymphoma.

OBJECTIVES: To assess the impact of second-look biopsy of residual mass during or after chemotherapy in pediatric mature B-cell NHL. METHODS: Patients with mature B-cell non-Hodgkin lymphoma (NHL) who were suspicious of radiological residual mass at mid or end of treatment and subjected to second biopsy were treated at our center between January 2001 and December 2015. Their clinical characteristics, imaging findings, pathological changes, management, and prognosis were reviewed retrospectively. RESULTS: A total of 31 children were included (13 boys and 18 girls, median age at diagnosis 6.1 years). The median time from diagnosis to second biopsy was 3.15 months (range 2.3-18 months). Biopsy confirmed the presence of viable tumor in eight patients. The specificity and positive predictive value of conventional imaging in detecting residual detectable by biopsy were at 9 and 28.6%, while sensitivity and negative predictive value of this approach were both 100%. Three of the histologic positive patients experienced progressive disease or relapse while the others achieved complete remission (CR) and 21 patients achieved long-time CR at median follow-up of 3.2 years. The median progression-free survival (PFS) time of all 31 was 28 months and 5-year PFS rate was 90.0%. Five-year PFS rate of negative-biopsy and positive-biopsy group were 100 and 62.5%, respectively (p = 0.002). CONCLUSION: Conventional imaging has very high sensitivity but very low specificity for the accurate determination of residual disease in pediatric NHL. Second-look biopsy is necessary to differentiate viable tumor from necrosis or fibrosis and is solid evidence-based foundation of subsequent treatment.

[Advances in targeted therapy for childhood acute myeloid leukemia].

At present, acute myeloid leukemia (AML) accounts for about 15%-20% of childhood acute leukemia. Although overall survival rate is increasing with the help of risk stratification, stratification of chemotherapy, and supportive treatment, conventional pharmacotherapy still has a limited clinical effect and certain limitations in improving remission rate in previously untreated patients and reducing recurrence after remission. With the development of precision medicine, the mechanisms of targeted therapy, including abnormal activation of AML-related signaling pathways and epigenetic modification, have been found in recent years. Molecular-targeted drugs can therefore act on specific receptors and target genes to improve clinical effect and the prognosis of AML patients.

Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001-2010.

BACKGROUND: This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China. PROCEDURE: From 2001 to 2010, 108 evaluable patients ≤16 years of age who were newly diagnosed with biopsy-proven LBL were treated with one of three treatment protocols: CCCG-99, SCMC-T-NHL-2002, or LBL-CHOF-2006. RESULTS: Two patients had Stage I disease, 5 had Stage II, 55 had Stage III, and 46 had Stage IV. The immunophenotype was T-cell LBL in 92 patients (85.2%) and precursor B-cell LBL in 16 (14.8%). The abandonment rate was 11.5%. Twenty-five patients (23.2%) suffered from resistant disease, including 1 with isolated central nervous system (CNS) relapse. At a median follow-up of 40.4 months (range, 0-114 months), the 5-year probability of event-free survival (pEFS) was 63.9 ± 4.6% in all patients. The 5-year pEFS for patients with pB-LBL was better than for patients with T-LBL (100% vs. 61.3 ± 5.1%, P = 0.007). Patients who had achieved complete remission on day 33 of induction had significantly better pEFS than those who had not (78.8 ± 4.6% vs. 28.2 ± 9.0%, P = 0.000). Three of 25 patients who experienced resistant disease were alive at the end of the study period. CONCLUSIONS: The abandonment rate was lower for patients with LBL than for patients with acute lymphoblastic leukemia. Prophylactic cranial radiation can be omitted for patients with LBL even when advanced-stage disease is present, as intensive systemic chemotherapy with intrathecal therapy is sufficient to prevent CNS relapse. The survival of patients with resistant disease was very poor.

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.

[Long-term follow-ups of comprehensive therapies for stage 4 neuroblastoma].

OBJECTIVE: To evaluate the long-term outcomes of childhood stage 4 neuroblastoma (NB) and its correlative prognostic factors. METHODS: Comprehensive protocols including tumor resection, intensive chemotherapy, radiotherapy, autologous bone marrow transplantation and 13-cis-retinoid were designed and implemented. A total of 112 newly diagnosed NB stage 4 patients at Shanghai Children's Medical Center collected from June 1998 to December 2010 were treated. Their clinical features, therapeutic efficacies, long-term outcomes and prognostic factors were analyzed. RESULTS: There were 69 males and 43 females with an age range of 4 months to 15 years. Among them, 12 improving patients didn't complete treatment because of parental decisions. Among those completing the comprehensive protocols, 62 cases (62.0%) achieved very good partial remission (VGPR), 20 (20.0%) achieved partial remission (PR) while another 18 (18.0%) progressed during treatment. The efficiency rate (including VGPR+PR) of treatment was 82.0 % (n = 82). The median follow-up period was 78 (56, 120) months. And 13 cases were lost after a median follow-up of 16 months. The 2, 3, 5-year event-free survival (EFS) was 56.2% (59/105) , 40.8% (40/98) and 21.1% (19/90) respectively. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated level of lactate dehydrogenase (LDH) (> 5 times normal value), bone marrow involvement and brain metastasis were poor prognostic factors (χ(2) = 12.01, 13.66, 6.29, 5.44, 16.18, all P < 0.05) . According to the multivariate estimates of hazards, age, high levels of LDH, poor curative effect and brain metastasis were associated with a worse survival (OR = 3.54, 1.89, 3.08, 3.45, all P < 0.05) . Brain metastasis predicted a worse outcome with 100% mortality rate (n = 6). Compared to traditional chemotherapy, topotecan-based chemotherapy could not improved the efficiency (52.6% (10/19) vs 63.2% (36/57) , P > 0.05) and long-term outcome (2 ys-EFS 42.1% (8/19) vs 56.4% (31/55) , P > 0.05). CONCLUSIONS: The prognosis remains poor for neuroblastoma of stage 4. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated LDH level (>5 times normal value) and bone marrow infiltration are associated with worse prognosis. Brain metastasis predicts the worst with 100% death rate. Topotecan included chemotherapy can not be proved more effective in this study.

HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a low platelet (PLT) count and a high risk of bleeding, the clinical treatment for which still needs to be upgraded. Based on the critical role of human leukocyte antigen class II heterodimer ß5 (HLA-DRB5) in immune system, we herein investigated its effect on ITP. ITP murine models were established by the injection of guinea pig anti-mouse platelet serum (GP-APS), and the PLT of mouse peripheral blood was counted during the modeling. Quantitative real-time reverse transcription polymerase chain reaction, western blot and immunofluorescence assay was performed to quantify expressions of HLA-DRB5, major histocompatibility complex II (MHC-II) and co-stimulatory molecules (CD80, CD86). Flow cytometry was conducted to analyze the percentage of CD8+ T cells. As a result, the PLT count was decreased in mouse peripheral blood. Expressions of HLA-DRB5, MHC-II and co-stimulatory molecules, as well as the percentage of CD8+ T cells were elevated in peripheral blood of ITP mice. HLA-DRB5 knockdown mitigated ITP by increasing peripheral PLT level, downregulating expressions of MHC-II and co-stimulatory molecules and inactivating CD8+ T cells. Collectively, the downregulation of HLA-DRB5 restores the peripheral PLT count in ITP mice by reducing MHC-II-mediated antigen presentation of macrophages to inhibit the activation of CD8+ T cells.

[Therapeutic efficacy of allogeneic hematopoietic stem cell transplantation in children with chronic myelogenous leukemia].

OBJECTIVE: To investigate the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with chronic myelogenous leukemia (CML), and to analyze the possible prognostic factors. METHODS: The clinical data of 20 children with CML who had received allo-HSCT was analyzed retrospectively to investigate possible prognostic factors, including age, sex, interval between diagnosis and transplantation, HLA matching between donors and recipients, illness status on transplantation and acute and chronic graft-versus-host disease (GVHD). RESULTS: At the end of follow-up, 13 of the 20 treated children had disease-free survival (DFS) and the rest (7 cases) died. Four died of severe acute GVHD, two of chronic GVHD and its complications, and one of relapse after transplantation. The three-year DFS was (64.6±1.1%). As shown by the univariate analysis, age was the most important prognostic factor in children with CML who had received allo-HSCT (P<0.05), and in children over 10 years, the prognosis was poor. No other of the above factors had a significant impact on prognosis (P>0.05). The multivariate logistic regression analysis also confirmed age as the only prognostic factor (P<0.01). Severe acute and/or chronic GVHD was the most important cause of patient death. 10/10 HLA-matched donors could improve the transplantation outcome. CONCLUSIONS: Allo-HSCT is an effective treatment for children with CML. To improve the prognosis and treatment outcome, children with CML aged over 10 years should receive allo-HSCT as early as possible. 10/10 HLA-matched donors are preferred in allo-HSCT and GVHD should be prevented.

[Evaluation on protocol SCMS-ALL-2005 for childhood B lineage acute lymphoblastic leukemia].

OBJECTIVE: To reduce the risk of therapy related complication during the treatment and keeps the long term event free survival, and to evaluate the results and risk factors of SCMC-lymphoblastic leukemia (ALL)-2005 protocol. METHODS: Designed the new protocol SCMC-ALL-2005 based on the previous protocol XH-99 for ALL. Divided the patients into low, median and high risk groups depends on risk factors including day 33 and 55 minimal residual disease (MRD) level. The higher risk group, the more intensive therapy was given. All the cases were registed on pediatric oncology network database (POND). All the abandonment patients were counted as event. From May 1(st) 2005 to April 30(th) 2009, 351 children who were newly diagnosed as B lineage ALL were enrolled in this study. The prognoses relating to risk grouping, age, mutation gene and MRD level were analyzed. RESULTS: Up to June 30, 2011, 273 patients were followed up with median time 49 months (range 26 to 74 months). Three hundred and forty-five patients (98.29%) achieved complete remission on day 35 induction. 12 cases were younger than 1 year old (3.42%), 285 cases between 1 and 9 years old (81.20%), 54 cases 10 to 18 years old (15.38%). Five year event-free survival (EFS) was 34%, 72% and 63%, respectively. One hundred and fifty-six cases belonged to lowered risk (44.44%), 177 to middle risk (50.43%) and 18 to higher risk (5.13%). Five year EFS was 78%, 64% and 30%, respectively. In this study, 18 patients were detected positive for BCR/ABL, 3 for MLL/AF4, 16 for PBX/E2A, and 36 for TEL/AML. The 5 year EFS were 11%, 66%, 75% and 74%, respectively. A total of 300 cases were tested for MRD levels on day 35. Of them, 241 cases were with MRD ≤ 0.01% (negative), and 59 cases > 0.01% (positive). The 5 year relapse free survival (RFS) was 79% and 58%, respectively. Total 6 patients died of complication (1.71%). 18 patients were abundant treatment with no disease progress. 70 patients relapsed (19.94%), including 52 bone marrow, 8 central nerve system (CNS), 1 both in bone marrow and CNS, 1 second cancer (M(4)) and 8 testis. Five year overall survival (OS) and EFS are 84% and 69%. CONCLUSIONS: The risk of therapy related death is low with the protocol SCMC-ALL-2005. MRD affects the prognosis. The long term prognosis is poor for high risk group, with BCR/ABL and positive MRD.

Early outcomes of primary repair versus reconstruction for acute anterior cruciate ligament injury: A systematic review and meta-analysis.

BACKGROUND: Contemporary techniques for repair of acute anterior cruciate ligament (ACL) rupture have been receiving renewed interest recently because of reports of good outcomes. METHODS: A literature search of PUBMED, MEDLINE, EMBASE, and the Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only RCTs published in English and comparing clinical outcomes of ACL repair versus reconstruction were included. Outcomes were evaluated using the International Knee Documentation Committee subjective score, Lysholm score, Tegner activity scale, visual analog scale pain score, anterior laxity, Lachman test, hop tests, knee injury and osteoarthritis outcome score, extension deficit, revision rate, and re-rupture rate. Statistical analysis was performed with Review Manager 5.4 and Stata 14.0. Two-tailed P < .05 was considered statistically significant. RESULTS: Four RCTs (with a total of 293 patients) that met the eligibility criteria were included in this review. Over short-term follow-up, none of the studies found significant differences between the repair groups and reconstruction groups with respect to International Knee Documentation Committee, Lysholm, Tegner, visual analog scale, anterior laxity, Lachman test, re-rupture rate, extension deficit, and performance of 3 hop tests (P > .05). In both groups, the hop tests scores were >90%. CONCLUSION: ACL repair and ACL reconstruction appear to provide comparable short-term outcomes. The low revision rate after primary repair is encouraging. For patients with ACL injury, current repair techniques such as dynamic intraligamentary stabilization and bridge-enhanced ACL repair may be an effective alternative to reconstruction.

[Therapeutic experience of childhood stage III neuroblastoma].

OBJECTIVE: To evaluate the long-term outcomes of childhood stage III neuroblastoma (NB) and its associated prognostic factors. METHODS: Children with newly diagnosed NB were enrolled into the protocol of NB-99 and followed up from January 1999 to May 2007. The relevant data were collected. And the statistics was processed by SPSS 10.0. RESULTS: Thirty children with stage III NB were found among all 101 children with NB. There were 19 males and 11 females. The mean age at diagnosis was (33 +/- 30) months. Abdomen and thorax were by far the most common sites of primary tumor (16 and 10 respectively). Twenty-one NB children had favorable pathology classification. Eleven NB children were treated according to the mediate-risk protocol, 6 children received autologous stem cell transplantation (ASCT) after chemotherapy and 5 patients had no therapy of cis-retinoic acid. Follow-up was conducted for 5 - 96 months. A complete response or an excellent partial remission was observed in 28 patients. Seven patients relapsed or progressed at the primary tumor site or bone marrow. The estimated cumulative probabilities of event-free survival and overall survival at 4 years for these 30 patients were 74% +/- 9% and 77% +/- 8% respectively. On univariate analysis, pathological type, high levels of LDH and ferritin, non-therapy of cis-retinoic acid were associated with a worse survival (chi2 = 9.48, 6.82, 9.17, 9.06, all P < 0.05). As to the multivariate estimates of hazards ratio, high levels of LDH and ferritin, no ASCT and non-therapy of cis-retinoic acid were associated with a worse survival (OR = 3.95, 3.44, 2.64, 1.27, all P < 0.05). CONCLUSION: Stage III NB children with favorable histologic features, normal LDH, normal serum ferritin, receive ASCT, and treated with cis-retinoic acid have a lower risk of relapse.

[Clinical observation on the treatment outcome of 14 children with hepatoblastoma in a single medical center].

OBJECTIVE: To evaluate the efficacy and safety of the ICE regimen (iphosphamide + carboplatin + etoposide) used in treating children with hepatoblastoma in the Shanghai Children's Medical Center. METHODS: From June 2000 to June 2008, 14 children with newly diagnosed hepatoblastoma (7 males and 7 females) were enrolled. Their median age on diagnosis was 1.33 years (range: 0.25-8.25 years). Six patients had stage I disease, 1 had stage II, 5 had stage III, and 2 had stage IV diseases. Thirteen children had markedly increased serum AFP level, and 1 had normal serum AFP level. Multidisciplinary co-operation treatment was performed. Eight patients had primary surgery while 3 patients had pre-operation chemotherapy before surgery. ICE chemotherapy regimen was used. Totally, 73 courses of chemotherapy were administered for the 14 children and 25 out of the 73 courses were performed before operation. RESULTS: Twelve patients responded to the treatment (85.7%) and 2 failed. Ten patients (71.4%) achieved complete remission after treatment, and two had partial remission. By July 31st, 2008, 9 patients survived without any event, with a median follow-up duration of 35 months (range: 16-96 months). The 5-year overall survival rate was 70.71+/-12.37%, and the 5-year event-free survival rate was 64.29+/-12.81%. One patient had disease relapse and two patients were lost to follow-up after they achieved partial remission. CONCLUSIONS: The ICE regimen combined with operation is effective and safe in treating children with hepatoblastoma.

Association of image-defined risk factors, tumor resectability, and prognosis in children with localized neuroblastoma.

BACKGROUND: Although localized neuroblastoma has a good prognosis, some cases have undergone treatment failure or recurrence. Apart from biologic features such as MYCN status, we wondered whether some characteristics of growing tumors are prognostic, such as a well-encapsulated mass without infiltration of vital organs. We analyzed the diagnostic utility of image-defined risk factors (IDRFs) to predict successful treatment and prognosis. The overall goal was to achieve maximum cure rates for patients with localized neuroblastoma through a better understanding of clinical characteristics. METHODS: We retrospectively reviewed the images of patients with localized neuroblastoma who were enrolled between June 1998 and December 2012 at a single institution in Shanghai, China. Unequivocal categorization regarding IDRFs was available in 67 patients. IDRF was assessed at diagnosis and after four cycles of neoadjuvant chemotherapy, on average. The median follow-up period was 84 months (range: 48-132 months) after diagnosis. RESULTS: MRI and CT indicated a total of 177 IDRFs in these 67 patients. Logistic regression analysis revealed a highly significant negative correlation between the numbers of IDRFs and the possibility of complete removal of neuroblastoma. Intraspinal extension of the tumor, compression of the trachea, and encasement of the main artery in localized neuroblastoma were predictors for incomplete tumor resection. According to univariate analysis, ≥ 4 IDRFs and intraspinal extension of the tumor were significant indicators of poor prognosis. CONCLUSIONS: The number of IDRFs was useful in predicting surgical outcome and event-free survival. The number of IDRFs should be considered in protocol planning, instead of IDRF presence or absence.

[Clinical importance of minimal residual disease testing in the therapy of childhood B-cell acute lymphoblastic leukemia].

OBJECTIVE: To study the role of minimal residual disease (MRD) in the evaluation of therapeutic effectiveness of childhood B-cell acute lymphoblastic leukemia (ALL). METHODS: MRD testing was performed in 124 children with B-cell ALL, who were newly diagnosed and enrolled in the ALL-XH-99 treatment protocol from September 2001 to April 2005MRD was determined by 4-color flow cytometry in the different time points during the treatment period. RESULTS: After induction therapy, 103, 13 and 8 patients showed MRD <0.01%, 0.01%-0.1% and >0.1%, respectively. The 5-year relapse-free survival (RFS) in the patients with MRD <0.01%, 0.01%-0.1% and >0.1% was 88.9+/-3.9%, 70.0+/-14.5% and 0%, respectively and the 5-year event-free survival (EFS) was 82.4+/-4.4%, 21.2+/-18.0% and 0%, respectively. There were significant differences in the RFS and EFS among the patients with different MRD levels (P<0.01). Within half a year after induction remission, the 5-year RFS in patients with MRD negative (<0.01%) and positive was 87.7+/-4.1% and 58.3+/-14.2%, respectively (P<0.01) and the 5-year RFS was 80.7+/-4.6% and 25.6+/-13.8%, respectively (P<0.01). After half a year with induction remission, the patients with MRD negative and positive also showed statistical differences in the 5-year RFS (92.0+/-3.6% vs 48.5+/-15.5%; P<0.01) and EFS (85.6+/-4.5% vs 21.4+/-11.0%; P<0.01). Multivariate analysis confirmed that the MRD level after induction chemotherapy together with the reaction to prednisone, the bone marrow features on the 19th day of induction, and the fusion gene with BCR-ABL or MLL-AF4 had prognostic significance in childhood B-cell ALL. CONCLUSIONS: The MRD level in the whole course of therapy is an important outcome indicator in childhood B cell ALL.

[Effectiveness of the AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia in children].

OBJECTIVE: To evaluate the effectiveness of AML-XH-99-M3 protocol for treatment of acute promyelocytic leukemia (APL) in children. METHODS: Thirty-three children with APL received AML-XH-99-M3 protocol treatment. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were evaluated by the Kaplan-Meier medthod with SPSS13.0 software. RESULTS: Thirty patients (90.9%) achieved a complete remission (CR) after one course of treatment. The total CR rate was 100%. Six patients (18.2%) relapsed in an average of 29.17 months (16-38 months). Two patients (6.1%) died. The 7-year EFS and DFS in the 30 patients were 73.4+/-9.4%. The overall survival rate was 91.2+/-6.0%. The difference of EFS was observed in patients receiving intermittent all-trans-retinoic acid (ATRA) administration or not in the maintenance therapy (88.9+/-10.5% vs 62.5+/-13.6%) (P<0.05). CONCLUSIONS: The AML-XH-99-M3 protocol for the treatment of APL produced a higher CR rate and higher EFS, DFS and OS rates in children. Intermittent administration of ATRA in the maintenance therapy can improve EFS rate.