Clinical Characteristics and Treatment Outcomes of Pediatric Patientswith Non-Hodgkin Lymphoma in East Asia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differfrom those of adults. This study delineated the characteristics and outcomes of pediatricNHL in East Asia. @*Materials and Methods@#Medical records of 749 pediatric patients with NHL treated at participating institutions inmainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 werereviewed. Demographic and clinical features, survival outcomes, and putative prognosticfactors were analyzed. @*Results@#Five hundred thirty patients (71%) were male. The most common pathologic subtypes wereBurkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases atdiagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%.The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphomawere 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheralT-cell lymphoma (PTCL) were 71% and 56% (p 250 IU/mL), and advanced disease at diagnosis( stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsedmore frequently than other pathologic subtypes (p < 0.001). @*Conclusion@#In East Asia, PTCL was more frequent than in Western countries, and bone marrow involvementdid not affect treatment outcome. This international study should motivate future collaborativestudy on NHL in East Asia.

Clinical effect of the SCMC APL-2010 regimen in treatment of acute promyelocytic leukemia in children: an analysis of 44 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect of the SCMC APL-2010 regimen in the treatment of acute promyelocytic leukemia (APL) in children.@*METHODS@#A retrospective analysis was performed for the clinical data of 44 children with APL who received treatment with the SCMC APL-2010 regimen between April 2010 and July 2016. The Kaplan-Meier survival analysis was used to evaluate event-free survival (EFS) rate and overall survival (OS) rate.@*RESULTS@#Of the 44 children with APL, 42 (95%) achieved a complete remission (CR) after one course of treatment and 1 achieved CR after two courses of treatment, with an overall CR rate of 98%. The 9-year EFS and OS rates were 96%±3% and 97.7%±2.2% respectively. As for adverse events, 41 (93%) had infection, 29 (66%) had granulocyte reduction, 12 (27%, 1 died) had differentiation syndrome, 16 (36%) had liver dysfunction, 12 (27%) had adverse gastrointestinal reactions, and 7 (16%) had QT prolongation, 1 (2%) had orchitis, and no secondary neoplasm was observed.@*CONCLUSIONS@#Children with APL receiving the SCMC APL-2010 regimen have a good prognosis and can achieve a long-term survival, while treatment-related infection is commonly seen.

Analysis of multicenter efficacy of acute lymphoblastic leukemia in older children / 中华血液学杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the clinical characteristics and the treatment outcomes of older children with acute lymphoblastic leukemia (ALL), and to evaluate the multicenter cooperation regimen (ALL-2005).</p><p><b>METHODS</b>The clinical data of 103 newly diagnosed ALL children aged 10 to 18 years old from five hospitals were enrolled in this study. They were all received ALL-2005 protocol. The clinical characteristics, the event-free survival (EFS), the overall survival (OS) and the prognostic analysis were evaluated.</p><p><b>RESULTS</b>(1) Of the 103 patients, 62 were boys and 41 girls, with a median age of 12.3 years old. According to immunophenotyping, 90 (87.4% ) of 103 patients were diagnosed as B-ALL and 13 (12.6%) as T-ALL. According to risk factor, 65 (63.1%) were in intermediate risk group (MR-ALL) and 38 (36.9%) in high risk group (HR-ALL). Central nervous system leukemia (CNSL) happened in 4 (3.9%) patients at diagnosis. Of the 89 patients received chromosome test, 58 (65.2%) obtained the test results, including 21(36.2%) with aberrational chromosomes and 37 (63.8%) with normal karyotype. Of 81 patients received molecular biological test, 16 (19.8%) were positive for fusion gene. (2) After induction therapy, 97 (94.2%) obtained complete remission (CR). Twenty-eight patients relapsed with a median time of 11.9 months (ranged 2.9-57.8 months), and 38 (36.9%) patients died during the treatment. As of September 30, 2012, the median follow-up was 47 months (ranged 0.4-92.6 months). The 5-year EFS and 5-year OS of ALL patients were (60.2 ± 4.8)% and(64.1 ± 4.7)%. The 5-year EFS of MR-ALL and HR-ALL were (73.8 ± 5.5)% and (31.6 ± 8.3)% (P<0.01), the 5-year OS of MR- ALL and HR-ALL were (78.5 ± 5.1)% and (35.9 ± 8.0)% (P<0.01), respectively. (3) Cox proportion hazard regression model analysis indicated that age of 14-18 years old and BCR- ABL translocation or t(9;22) were independent risk prognostic factor for 5-year EFS.</p><p><b>CONCLUSION</b>The incidence and prognosis in older childhood ALL were related with age, risk and biological characteristics. BCR-ABL translocation or t(9;22) was the risk factor of prognosis. ALL- 2005 protocol was recommended as the regimen for older childhood ALL.</p>

Long-term follow-up of childhood low-risk ALL patients treated with SCMC-ALL-2005 protocol / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the long-term efficacy of SCMC-ALL-2005 protocol in treatment of low-risk childhood acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>From May 1, 2005 to April 30, 2009, 387 patients enrolled into SCMC-ALL-2005 protocol. Based on the characteristics of cell morphology, immunology, cytogenetics and molecular biology and treatment response, 158 patients were fit into the low-risk treatment group. All the cases were registered in pediatric oncology network database (POND). The clinical characteristics and outcome were analyzed.</p><p><b>RESULTS</b>Until December 31, 2012, the 5-year event free survival (EFS) and overall survival (OS) is (77.76±3.37)% and (89.55±2.83)%, respectively. Median follow-up time is 5.33 y (3.75-7.70 y). Five patients (3.16%) died of complication, all of them were severe infections. Twenty-seven patients (17.09%) relapsed, including 13 bone marrow relapse (8.23%), 5 testis relapse (5.32% of boys, 2 of unilateral and 3 bilateral), 6 central nerve system relapse (CNS, 3.80%), 1 relapse in both bone marrow and CNS, 1 relapse in both bone marrow and testis, and 1 right ovary and fallopian tube relapse. Relapse is related to positive minimal residual disease. Two cases (1.27%) occurred second tumors, 4 patients (2.53%) gave up treatment in complete remission without special reasons.</p><p><b>CONCLUSION</b>The EFS and life quality of SCMC-ALL-2005 protocol in the treatment of childhood low-risk ALL is satisfactory. The treatment-related mortality rate is lower, and the long-term EFS is higher than that of XH-99 protocol.</p>

Long-term outcomes of childhood lymphoblastic lymphoma: report of 70 cases / 中华血液学杂志

<p><b>OBJECTIVE</b>To summarize long-term outcomes of childhood lymphoblastic lymphoma (LBL) with protocol CCCG-97 and -2002.</p><p><b>METHODS</b>From November 1998 to October 2010, 70 consecutive newly diagnosed childhood LBL (5 B-LBL and 65 T-LBL) were enrolled in this study, in which 22 received CCCG-97 and 48 CCCG-2002 protocols. St.Jude staging system was adopted. Patients were divided into three risk groups based on clinical stage and serum LDH, and received chemotherapy with different intensity. The factors, which were possibly associated with the prognosis, were analyzed. The survival rates were evaluated by Kaplan-Meier analysis.</p><p><b>RESULTS</b>The patients were 1.5 to 14 years old with the median age of 8 years old. They were evaluated as stage I-II for 6 , stage III41, and stage IV23 (15 were BM positive and 8 multiple bone metastases). Until Dec.31th, 2011,the mean follow-up was 62.5 months (range, 14 to 161 months) with the median follow-up of 48 months. 1-year overall survival (OS) was 74.3%, and 5- year event-free survival (EFS) 64.1% (abundance as event). Thirteen patients were complicated with serious condition during chemotherapy and 1 died of complication. Univariate analysis indicated that delayed and/or non-completed response on days 33 and 63 of induction was the unfavorable prognostic factor.</p><p><b>CONCLUSION</b>Primary LBL usually located in the mediastinum. 90% of the patients was at advanced stage III-IV at first presentation. The 5-year EFS was 64.1%. Patients not achieved CR at days 33 and 63 at the end of induction was a poor prognostic factor.</p>

ALL-2005 protocol experience in the therapy of children and adolescents over 10 years of age with acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the incidence, clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>From May 1, 2005 to April 30, 2009, 67 newly diagnosed ALL children and adolescents over 10 years of age were enrolled in protocol of ALL-2005. All of the clinical characteristics of the patients were analyzed. The statistics was done by SPSS 13.0.</p><p><b>RESULTS</b>There were 40 males (59.7%) and 27 females (40.3%). The mean age at diagnosis was 12.3 ± 1.7 (10.0 to 17.8) years with median age of 12.2 years. Of 67 patients, 48 were in medium risk group, and 19 in high risk group. During induction therapy, 83.6% and 86.6% patients had good response to prednisone and bone marrow blasts ≤ 5% at day 19, respectively. The overall hematologic response rate in these 67 patients was 88.1% (59) in complete remission (CR) after induction therapy, 15 patients relapsed with mean continuous CR period of (14.9 ± 9.9) months. The five-year event-free survivals (EFS) and overall survivals (OS) were (64.4 ± 6.3)% and (74.1 ± 6.1)%, respectively. According to univariate analysis, elevated serum ferritin, bcr-abl translocation, poor response to prednisone, high bone marrow blasts at day 19 or after induction therapy, and high minimal residual disease (MRD) after induction therapy increased risk for recurrence. Multivariate analysis indicated that high MRD after induction therapy was associated with recurrence (RR = 2.20, 95%CI 1.26 - 3.84, P < 0.01).</p><p><b>CONCLUSION</b>Survival has improved for children and adolescents with ALL by ALL-2005 protocol. Analysis of serum ferritin and bcr-abl translocation at diagnosis, early responses to treatment and MRD detection during therapy are powerful prognostic indicators.</p>

Correlation between blood T-cell receptor rearrangement excision circles levels and severe infection in children with acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study quantitatively examined signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels in peripheral blood of children with acute lymphoblastic leukemia (ALL) at different stages in order to evaluate the role of sjTRECs in predicting severe infection postchemotherapy.</p><p><b>METHODS</b>sjTRECs levels in peripheral blood were measured by fluorescent quantitation-polymerase chain reaction in 30 children with newly diagnosed ALL, 36 children with ALL who accepted chemotherapy but were not infected, 30 children with ALL who had severe infection after chemotherapy, and 50 normal children.</p><p><b>RESULTS</b>Blood sjTRECs levels in the normal group (394 ± 270 copies/103 MNC) were significantly higher than those in the other three groups (P<0.05). Blood sjTRECs levels in the chemotherapy group without infection (96 ± 78 copies/103 MNC) were significantly lower than those in the newly diagnosed ALL group (210 ± 219 copies/103 MNC) (P<0.05). The chemotherapy group with severe infection showed the lowest blood sjTRECs levels (48 ± 40 copies/103 MNC) in the four groups.</p><p><b>CONCLUSIONS</b>The measurement of blood sjTRECs levels might be helpful for predicting the occurrence of severe infection postchemotherapy in children with ALL.</p>

Evaluation of early monitoring of cardiotoxicity induced by anthracyclines / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Anthracyclines (ANT) are effective for leukemia and solid tumors. However the long-term life quality of patients is seriously affected by ANT-related cardiotoxicity. The aim of this study was to evaluate the value of two dimension echocardiography (2DE) and serum biochemical indicators in monitoring ANT-related cardiotoxicity.</p><p><b>METHODS</b>Seventy children who received ANT chemotherapy (ANT dose: 124 ± 73 mg/m2) and were followed up for 22 ± 13 months were enrolled. 2DE with aspects of conventional indexes (left ventricular diameter and wall thickness, ejection fraction, E/A), myocardial performance index (MPI) and tissue Doppler imaging (TDI) were performed. Serum levels of troponin (CTnI) and brain natriuretic peptide (BNP) were measured. Thirty-seven healthy children served as the control group.</p><p><b>RESULTS</b>There were no significant differences in conventional indexes of 2DE between the ANT and the control groups. The MPI of left and right ventricular in the ANT group increased significantly compared with that in the control group (0.237 ± 0.06 vs 0.203 ± 0.06, 0.171 ± 0.05 vs 0.140 ± 0.04 respectively; P<0.01). TDI showed the late diastolic peak velocity in the basal and middle sections of left ventricular, interventricular septum and right ventricular in the ANT group were significantly higher than the controls. There were significant differences in the ratio of early to late diastolic peak velocity of the middle section of left ventricular and the basal and middle sections of the interventricular septum between the two groups (P<0.05). The changes of MPI and TDI became more obvious with the increased dose of ANT. There were no significant differences in serum CtnI and BNP levels between the two groups.</p><p><b>CONCLUSIONS</b>The heart function of patients who received ANT chemotherapy needs to be monitored for a long term. MPI and TDI can be used as early indexes for monitoring the heart function.</p>

Analysis of clinical outcomes of 63 children with acute monocytic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the outcomes of childhood acute monocytic leukemia (AML-M5) and explore the indications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for children with AML-M5.</p><p><b>METHOD</b>Seventy-five AML-M5 patients and 201 non-AML-M5 AML patients were enrolled in this retrospective analysis. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by COX regression with SPSS.</p><p><b>RESULT</b>(1) Twelve patients gave up treatment after confirmed diagnosis. Two patients died on the second day after chemotherapy. Of the 61 patients, 73.8% (45/61) achieved complete remission (CR) after two courses of chemotherapy. The 5-year EFS rate was 34.5% ± 6.8%. But of the 117 non-AML-M5/M3 AML patients, the 5-year EFS rate was 51.0% ± 4.9%. (2) Multivariate analysis showed that age ≥ 10 y, the proportion of bone marrow blast cell counts ≥ 15% after the first induction therapy, not CR after two courses of chemotherapy were risk factors for the long-term prognosis. (3) Of the 20 patients whose bone marrow blast cell counts ≥ 15% after the first induction therapy, 5 patients who choose allo-HSCT had a better OS than the other 15 patients who choose chemotherapy only (60.0% ± 21.9% vs. 7.3% ± 7.1%, P = 0.024).</p><p><b>CONCLUSION</b>Children with AML-M5 had a poorer prognosis than the other AML patients; patients whose bone marrow blast cell counts ≥ 15% after the first induction therapy chose allo-HSCT had a better prognosis. At present, there is no enough evidence to support that patients whose bone marrow blast cell counts < 15% after the first induction therapy should choose unrelated donor for allo-HSCT.</p>

Clinical report on protocol HL-98 for childhood Hodgkin's Lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the long-term prognosis of childhood Hodgkin's lymphoma (HL) by standard treatment protocol HL-98.</p><p><b>METHODS</b>Patients were divided into low (R(1)), middle (R(2)) and high-risk (R(3)) groups based on staging, tumor size and with or without B symptoms. Patients of R(1), R(2) and R(3) groups were given 4, 6, and 9 courses of chemotherapy, respectively. Low dose radiotherapy to involved area was given to patients with residual disease at the end of chemotherapy. All patients diagnosed between 1998 and Dec. 2008 were enrolled. The software of SPSS 11.0 was used and the event free survival (EFS) was generated by Kaplan-Meier.</p><p><b>RESULTS</b>There was a total of 26 patients with male 20 and female 6. The average age was 97 (30 to 179) months and median age 94.5 months. Three patients were in stage I, 4 in stage II, 9 in stage III and 10 in stage IV. Of 26 patients, 24 were found with neck tumor, 12 with mediastinum tumor, 11 with spleen infiltration and 5 with B symptom. Four patients were allocated into R(1) group, 12 R(2) group and 10 R(3) group. Eight of 26 with residual disease received radiotherapy, 7 received 20-26 Gy and 1 received 36 Gy. To Jun 2009, 21 (80.76%) of them kept in complete remission (CR) at 10 to 120 months follow-up (average 36 months, and median 31 months). Five cases relapsed (1 of stage III and 4 of stage IV) within 5 to 12 months. Three out of 4 in stage IV with B symptom relapsed. The estimated 5-year overall survival (OS) was 85.9% and EFS was 73.7%.</p><p><b>CONCLUSION</b>The estimated 5-year EFS indicated that protocol HL-98 is reasonable good. Patients of stage I and II can obtain a good prognosis without radiotherapy.</p>

Treatment outcomes of 125 children with aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the outcome of childhood aplastic anemia received allogenic hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST).</p><p><b>METHODS</b>The clinical data of 125 consecutive children with aplastic anemia (AA) in our hospital were retrospectively analyzed.</p><p><b>RESULTS</b>According to the clinical manifestations, the 125 AA children were divided into two groups: SAA (n = 79) and NSAA (n = 46). There was no significant difference between the two groups in sex, age and follow-up duration (P > 0.05). The median follow-up was 25 (6 - 89) months. 103 cases received IST and 22 received allogenic HSCT. In SAA group, the response rate was better in patients received allogenic HSCT (n = 21) than in those received IST (n = 58) (85.7% vs 53.4%, P < 0.01). SAA patients received IST were further divided into two groups: 47 received antithymocyte globulin (ATG) and cyclosporine-A (CsA) combined therapy, 11 received CsA alone. There was no significant difference in total response rates (55.3% vs 45.5%, P = 0.555) and cure rates (42.6% vs 27.3%, P = 0.499) between the two groups. In NSAA group, 45 patients received IST and 1 received allogenic HSCT. In the IST treated NSAA patients, there was also no statistic significance in cure rates (36.4% vs 32.4%, P = 0.806) and total effective rates (63.6% vs 64.7%, P = 0.949) between ATG and CsA combined therapy (n = 11) and CsA alone therapy (n = 34).</p><p><b>CONCLUSION</b>The outcome of children with AA received allogenic HSCT was obviously better than those received IST. IST is still the choice for patients without suitable donors for HSCT.</p>

Study on NPM1 gene mutations in childhood acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To examine the incidence and clinical significance of NPM1 mutations in childhood acute myeloid leukemia (AML) patients.</p><p><b>METHODS</b>NPM1 mutations of 70 newly diagnosed childhood AML were detected by high resolution melting (HRM) analysis on the LightCycler 480. The incidence and clinical significance were analyzed.</p><p><b>RESULTS</b>NPM1 mutations were identified in 32 (45.7%) of the 70 AML children. There was no significant difference in clinical characteristics between patients with or without NPM1 mutation, but patients with NPM1 mutation had a higher platelet count (P = 0.013). There was also no significant difference in NPM1 mutation between normal and abnormal karyotype groups. In AML-ETO or PML-RARα positive groups, the incidence of NPM1 mutations was significant lower (P = 0.048). There was no significant difference in response rates after induction therapy (P = 0.217), but the complete remission (CR) rate was higher in the NPM1-mutated group (81.3%). There was a trend toward higher event-free survival (EFS) and overall survival (OS) rates in the NPM1 mutated patients than that in wild NPM1 patients (EFS = 53.8% vs 41.4%, OS = 52.7% vs 39.2%), but the difference was not statistically significant (P = 0.374 and 0.380).</p><p><b>CONCLUSION</b>NPM1 mutations were relatively common in our cohort of AML patients. There was no significant difference in clinical characteristics between patients with and without NPM1 mutation. The NPM1 mutation patients group seemed to have better therapy response, but the difference was not statistically significant.</p>

The cultivation and identification of tumor stem cells from neuroblastoma derived tumor spheres / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Since the proposal of the tumor stem cell hypothesis, considerable interest has been devoted to the isolation and purification of tumor stem cells. Tumor stem cell enrichment from primary tumor derived cell spheres has been demonstrated in specific, serum-free media. This goal of this study is to establish a method of cultivating floating tumor spheres from neuroblastoma cells and to confirm that neuroblastoma spheres are rich in tumor stem cells.</p><p><b>METHODS</b>Bone marrow aspirates were obtained from pediatric patients diagnosed with stage IV neuroblastoma. Primary tumor cells were isolated and cultivated in serum-free, stem cell-selective medium. Single sphere-forming cells were cultivated under serum-free conditions; their cloning efficiency and monoclonal tumor sphere formation rates were calculated. The expression of stem cell marker genes Oct-4 and Bmi-1 was detected by RT-PCR in sphere-forming cells and parental neurolastoma cells. Sphere-forming cells were injected into the armpit of nude mice with subsequent assessment for tumor growth. Sphere-forming cells were cultivated in differentiation medium containing 5 μmol/L 13-cis retinoic acid; changes in cell morphology were observed.</p><p><b>RESULTS</b>Neuroblastoma cells formed non-adherent neurospheres under serum-free, stem cell-selective conditions after a period of 4 to 6 days. A single cell dissociated from a neurosphere could reform a monoclonal sphere; cloning efficiency and monoclonal sphere formation rates were 55.3% and 26.3%, respectively. RT-PCR results revealed heightened tumor sphere expression of Oct-4 and Bmi-1 as compared with parental tumor cells. Fourteen days after injection of 10(4) sphere-forming cells into nude mice, a neuroblastoma xenograft formed. Treatment of sphere-forming cells with 13-cis retinoic acid induced a gradual differentiation to neuronal cell morphology.</p><p><b>CONCLUSIONS</b>Neuroblastoma derived tumor spheres enrich tumor stem cells and the cultivation of primary neuroblastoma cells in serum-free, stem cell-selective medium is an effective method to dissociate and purify tumor stem cells in vitro.</p>

An epidemiological survey of acute lymphocytic leukemia from 2002 to 2006 in Shanghai / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the epidemiological data of acute lymphoblastic leukemia (ALL) in Shanghai.</p><p><b>METHODS</b>ALL cases in Shanghai from 2002 to 2006 were retrospectively investigated.</p><p><b>RESULTS</b>All together there were 544 newly diagnozed ALL cases. The yearly incidence of ALL was 0.81/10(5), which was slightly higher in men (0.86/10(5)) than in women (0.75/10(5)). The age-stratified incidence showed 2.31/10(5) in patients (pts) </= 17y, 0.54/10(5) in 18 - 34 y, 0.46/10(5) in 35 - 59 y, and 0.94/10(5) in pts > 60 y. The incidences in Chongming County was 0.60/10(5), being the lowest in all districts. The morphological types of ALL was L(1) (26.2%), L(2) (57.4%) and L(3) (16.4%); the immunophenotype was B (80.1%) and T (19.5%). The incidence of ALL with myeloid antigen expression was 20.2%. Genetic examination revealed that chromosome aberration of t(9;22) was the most common one.</p><p><b>CONCLUSIONS</b>The incidence of ALL in Shanghai is 0.81/10(5). Compared with the national standard (1986 - 1998), the incidence in adolescents is obviously increased. Chongming County has the lowest incidence, indicating a role of environment factor in ALL incidence.</p>

Outcome of 46 children with refractory leukemia treated with unrelated donor hematopoietic stem cell transplantation / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of matched unrelated donor hematopoietic stem cell transplantation (UDT) and influencing factors in children with refractory leukemia.</p><p><b>METHOD</b>Retrospective analysis was performed on clinical data of 46 consecutive children received UDT between Nov. 2002 and Dec. 2008. A 12-14 GY fractioned total body irradiation (TBI) was given to children with acute lymphoblastic leukemia (ALL). Busulphan based myeloablative regimen was applied to all the other patients. ATG (Fresenius) 15 - 20 mg/kg + low dose cyclosporine A oral [CSA, 8 - 12 mg/(kg * d) with serum trough levels 150 - 200 ng/ml] +/- methotrexate (without methotrexate for cord blood transplant) were administered as graft versus host disease (GVHD) prophylaxis. Mycophenolate mofetil [MMF, 20 - 30 mg/(kg * d)] was added for 13 CML after Jan 1, 2006 because of more severe GVHD was observed in this group.</p><p><b>RESULTS</b>The median age was 8.0 (2 - 17) years with the median follow up period of 23.5 (0.7 - 85) months. The estimated 3 years overall survival (OS) was 63.0%; 23.9% patients died of transplant related mortality, 13.0% patients died of leukemia relapse. Cytomegalovirus (CMV) infection recurred in 50% patients and hemorrhagic cystitis in 15.2% patients; 33.3% patients developed grade III-IV acute GVHD and 55.6% developed chronic GVHD (13.9% with extensive chronic GVHD). The OS was significantly different between the patients older (n = 20) and younger (n = 26) than 10 years (45.0% vs. 76.9%, P = 0.015) and among the patients with ALL (n = 13), CML (n = 18) and AML (n = 15) (38.4%, 66.7% vs.80.0%, P = 0.034). The OS in patient with high risk leukemia (n = 24) was lower than that in the patient with low risk leukemia (n = 22) (45.8% vs. 81.8%, P = 0.012). Except 8 cord blood transplant the OS of patients with HLA 6/6 high resolution completely matched (n = 16) and 1/6 mismatched (n = 16) bone marrow and peripheral blood stem cell transplants was significantly higher than patients with 2/6 mismatched (n = 6) UDT (75.0%, 75.0% vs. 16.7%, P = 0.007). But the OS was not significantly different between patients with grade 0-II acute GVHD and III-IV acute GVHD (60.0% vs. 66.7%, P = 0.494).</p><p><b>CONCLUSION</b>The outcome of UDT for Chinese children with refractory leukemia is encouraging. Patients younger than 10 years with 0-1/6 high resolution mismatched UDT had the best OS. The outcome of patients with myeloid and low risk leukemia is superior to those with other types of leukemia.</p>

Causes of deaths of children with malignant tumors during hospitalization in a single center / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the main causes of deaths and the influencing factors in children with malignant tumors in the hospital, explore the possible way to improve the treatment.</p><p><b>METHODS</b>Clinical data of 84 patients with malignant tumors who died during hospitalization in the Department of Hematology/Oncology from June 1999 to December 2008 were collected and retrospectively analyzed. Major causes of deaths and their influencing factors were analyzed.</p><p><b>RESULTS</b>(1) Treatment related complications which occurred in 73 cases (86.9%) were the leading cause of death, including infection-related death which was the most common cause of 51 cases (60.7%), hemorrhage-related death occurred in up to 28 cases (33.3%), and acute tumor lysis syndrome (ATLS) related death occurred in 2 cases (2.4%), graft versus host disease (GVHD) related death after allogeneic hematopoietic stem cell transplantation occurred in 4 cases (4.8%). Moreover, primary diseases related death occurred in 30 cases (35.7%). (2) In this group, there were no significant differences in treatment phases when the death occurred among patients with leukemia (56 cases), lymphoma (9 cases) and other non-hematopoietic and lymphoid tissue tumors (7 cases, chi(2) = 4.784, P = 0.310). (3) The infection related death increased significantly when WBC count was lower than 1.0 x 10(9)/L, which is totally different from those whose WBC was higher than or equal to 1.0 x 10(9)/L (chi(2) = 25.486, P < 0.001). (4) Twenty-six cases were detected to be infected with definite pathogens; different pathogens were identified 36 times in the 26 patients. Gram-negative bacteria (15/36, 41.7%) were the most common pathogens, followed by fungal organisms (14/36, 38.9%) and gram-positive bacteria (7/36, 19.4%).</p><p><b>CONCLUSION</b>More attention should be paid to the prevention and treatment of cancer therapy related complications in children with malignant tumors. Infection was the leading cause of death, gram-negative bacteria and fungi were predominating pathogens. Application of effective antibiotics and combined antifungal drugs timely, especially in the remission induction or first chemotherapy period as well as in the period of neutropenia, may reduce mortality of children with malignant tumors significantly.</p>

Clinical characteristics and treatment outcome of 36 cases with non-Hodgkin's lymphoma arising from mediastinum in children / 中华儿科杂志

<p><b>OBJECTIVE</b>Non-Hodgkin's lymphoma (NHL) presenting as mediastinal mass is usually progressive and may cause severe respiratory distress and death. This study aimed to summarize the clinical features and prognosis of NHL arising from mediastinum.</p><p><b>METHODS</b>Totally 36 patients with NHL arising from mediastinum reported herein were diagnosed between 1999 and 2007. Their clinical characteristics, pathologic classification, diagnosis, outcome of different treatment protocol were retrospectively analyzed. Of these 36 patients, 25 were male, 11 were female (2.2:1). The mean age was 7.9 (range 1 - 12) years. Diagnosis was established on pathology that was achieved by mediastinal mass or peripheral lymph nodes biopsy, while some were diagnosed based on bone marrow or pleural effusion cytology study and immunophenotyping. For staging, the St. Jude system was applied. Patients received T-NHL-CCCG97, T-NHL-2002 or B-NHL-2001 protocol according to morphology and immunophenotyping. Patients who experienced superior vena cava syndrome (SVCS) and/or superior mediastinum syndrome (SMS) received induction chemotherapy with cyclophosphamide (C), vincristine (O) and prednisone (P) for one week.</p><p><b>RESULTS</b>Twenty-seven cases experienced mediastinal mass or peripheral lympho nodes biopsy and were diagnosed by histopathology and immunohistochemistry. Of them, 24 were lymphoblastic lymphoma and 3 were anaplastic large cell lymphoma. Nine patients were diagnosed by cytological study of bone marrow aspiration or pleural fluid. All the 36 cases were T-cell type. Twenty-four cases were in stage III, 12 in stage IV. Twenty-four patients had urgent situation of SVCS and airway obstruction, 22 patients reached good response after emergency management including COP induction chemotherapy and pleural effusion suction. Twenty-nine cases achieved complete remission (CR) while in 6 patients the disease relapsed. Thirteen patients died from disease progression, relapse or severe infection during chemotherapy. The Kaplan-Meier estimate of 5-year progression-free survival (PFS) was 61% +/- 8% (median follow up 35 months) for these 36 patients.</p><p><b>CONCLUSION</b>Establishment of a diagnosis as soon as possible was important to reduce the mortality and improve long term survival of patients. Induction chemotherapy for emergency situation was efficacious. The regimen of T-NHL-CCCG97, T-NHL-2002, and B-NHL-2001 for NHL arising from mediastinum based on pathological classification is feasible.</p>

Clinical report on diagnosis and treatment of 14 cases with pediatric Ewing's sarcoma family tumors / 中华儿科杂志

<p><b>OBJECTIVE</b>To recognize and improve the outcome of childhood Ewing's sarcoma family tumors, and to identify the efficacy and safety of the chemotherapy using RS-2002 Protocol.</p><p><b>METHODS</b>From September 1997 to September 2006, 14 newly diagnosed patients with the tumors were admitted, 9 were boys, and 5 were girls, the median age was 7.04 years, ranging from 1.58 years to 11.67 years. Among them, 9 patients were younger than 10 years. By the time of diagnosis, 9 patients had local diseases, and the other 5 patients had metastatic diseases. All the patients' diagnoses were confirmed by pathological studies. Nine patients had Ewing's sarcoma by histology, and the other 5 patients had peripheral primitive neuroectodermal tumors (PPNET). All of the patients were treated with multidisciplinary therapy, and RS-2002 Protocol for chemotherapy was used to treat patients with rhabdomyosarcoma in our hospital. Surgery and irradiation were performed for local control. Imaging studies were used for evaluation, reevaluation and follow-up.</p><p><b>RESULTS</b>Till April 30th 2007, 13/14 patients survived. The median follow-up time was 41 months (range: 7 months-115 months). The 10-year overall survival (OS) was 88.9%+/-10.5%, and the 10-year disease-free-survival (DFS) was 72.2%+/-13.8%; 3/14 patients had disease relapse, the median time to relapse from initial diagnosis was 23 months (range: 16-30 months). One patient developed second malignancy. No therapy related death was documented.</p><p><b>CONCLUSIONS</b>Childhood Ewing's sarcoma family tumors were not very rare, and the prognosis was acceptable with optimal treatment. RS-2002 Protocol was effective and safe in treating such patients.</p>

Relationship between immunological characteristics and prognosis in children with acute myeloid leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The prognostic significance of immunophenotyping in acute myeloid leukemia (AML) has been controversial. This study investigated the relationship of immunophenotypes with French-American-British (FAB) subtypes and chromosomal abnormalities and assessed the prognostic value of immunophenotyping in children with AML.</p><p><b>METHODS</b>From January 1998 to May 2003, 75 children with newly diagnosed AML were enrolled on protocol AML-XH-99. Immunophenotypes were measured with the flow cytometry. According to the McAbs used, the patients were classified into five groups: panmyeloid antigens (CD13, CD33, and MPO), myeloid-lineage associated antigens (CD14, CD15), lineage-specific antigens (CD41, GlyA), progenitor-associated antigens (CD34, HLA-DR) and lymphoid-associated antigens (CD19, CD7). The probability of event-free survival (EFS) was estimated by Kaplan-Meier analysis. The distributions of EFS were compared using the log-rank test. Chi-square analysis or Fisher exact test was used to compare the differences in the distribution of biologic presenting features. A Cox proportional hazards model was used to identify independent prognostic factors.</p><p><b>RESULTS</b>At least one of panmyeloid antigens CD13, CD33 and MPO was expressed in 72 patents (97.3%). Two or more panmyeloid antigens were expressed in 45 patients (60.8%). The proportion of children with AML expressing one or more of the lymphoid-associated antigens was 24.3%. Lymphoid-associated antigen CD19 was expressed by blast cells in most of FAB M2 patients. The patients with acute promyelocytic leukemia were characterized by the absence of HLA-DR and lymphoid-associated antigens CD19 and CD7. Monovariate analysis showed immunophenotypes were not related to the complete remission rate after the first induction course and the 5-year-EFS. Multivariate analysis suggested immunophenotyping had no independent prognostic value in AML.</p><p><b>CONCLUSIONS</b>Immunophenotyping can not be used independently in the evaluation of risk classification in children with AML. However, it is useful in the reorganization of special types of AML.</p>

Tandem application of flow cytometry and polymerase chain reaction for choice targets of minimal residual disease in childhood acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Minimal residual disease (MRD) is one of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL). Flow cytometry and PCR are two common techniques for examining MRD in ALL. This study aimed to identify MRD targets by tandem application of both techniques in children with ALL.</p><p><b>METHODS</b>From September 2001 to October 2003, 126 children with newly diagnosed ALL were enrolled on the treatment protocol ALL-XH-99. Tandem application of flow cytometry and PCR was performed to identify MRD targets in these patients.</p><p><b>RESULTS</b>1. Using sets of combined antibodies, immunophenotypic expression of leukemia cells was observed in 95 of 106 B-lineage ALL cases (89.6%). Only one aberrant immunophenotype was observed in 11 cases (11.6%) and most patients with B-lineage ALL (88.4%) expressed at least two suitable targets. 2. Using PCR technique, T-cell receptor (TCR) or immunoglobulin gene rearrangements were identified in 26 of 27 patients (96.3%). Two or more monoclonal/ bi-allelic gene rearrangements were identified in 17 cases (65.4%). The majority (70%) of T-lineage ALL cases contained TCRVgammaI-Jgamma1.3/2.3. Cross-lineage TCR rearrangements were found in 57.1% of cases with B-lineage ALL. 3. Suitable MRD targets of immunophenotypic abnormalities or antigen receptor gene rearrangements were detected in 121 patients (96.0%).</p><p><b>CONCLUSIONS</b>MRD targets were identified using tandem application of flow cytometry and PCR in almost of children with ALL. Cross-lineage TCR rearrangements and bi-allelic gene rearrangements were observed in many patients.</p>