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.

Outcomes of 104 children with B-cell non-Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze outcomes and prognostic factors of children with B-cell non-Hodgkin lymphoma (B-NHL).</p><p><b>METHODS</b>One hundred and four newly diagnosed B-NHL children were enrolled in protocol of B-NHL 2001. The statistics were performed by SPSS 13.0.</p><p><b>RESULTS</b>Of 104 children (79 males, the median age of 7.1 years), 60, 32 and 4 patients were diagnosed with Burkitt lymphoma, diffuse large B-cell lymphoma and unclassifiable B-cell lymphoma, respectively. Four patients were in stage Ⅰ, 27 stage Ⅱ, 55 stage Ⅲ and 18 stage Ⅳ; 1, 26 and 77 patients were allocated into R1, R2 and R3 risk groups, respectively. Three patients never got complete remission (CR), 9 patients relapsed after CR with the duration of relapse from 1 to 7 months after chemotherapy. The estimated 5-year EFS of 104 patients was (86.7 ± 3.5)%. Univariable analyses identified that risk factors for recurrence were of higher staging, elevated LDH, serum ferritin and poor early response. Age, sex, pathologic diagnosis, original tumor, bone or marrow involvement, C-MYC and risk group were not found to be associated with the risk of failure to treatment. Multivariable COX regression models confirmed serum ferritin as a significant independent prognostic marker.</p><p><b>CONCLUSION</b>B-NHL 2001 protocol was reasonable for B-NHL children. Higher staging, elevated LDH, serum ferritin and poor early response increased risk for recurrence.</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>

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>

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>

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 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>

ALL-XH-99 protocol in the treatment of childhood T-cell acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the incidence, clinical characteristics and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).</p><p><b>METHODS</b>From January 1999 to April 2005, 305 patients with newly diagnosed ALL were enrolled in protocol ALL-XH-99. The clinical characteristics of these children were analysed.</p><p><b>RESULTS</b>Of 305 childhood ALL patients, 43 were T-ALL. There were 34 males among the 43 T-ALLs. The mean age at diagnosis was 7.8 (2.2 to 16.4) years, 29 (67.4%) cases of them were older than 10 years, and 27 (62.8%) cases had initial WBC count more than 50 x 10(9)/L. In comparison with that of B cell ALL (B-ALL), the percentages of age older than 10 years, initial WBC count more than 50 x 10(9)/ L, prednisone poor response (PPR), and failed to achieve remission at day 19 of induction chemotherapy in the T-ALLs were all higher. No statistic difference was found in sex between them. The eight-year event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS) were (40.2 +/- 10.1)%, (51.4 +/- 11.6)% and (49.8 +/- 9.9)% for T-ALL, and (72.1-3.0)%, (83.2 +/- 2.7)%, and (76.6 +/- 2.9)% for B-ALL, respectively, being differed significantly between the two types of ALL (P < 0.01).</p><p><b>CONCLUSION</b>There were statistic differences between T-cell and B-cell childhood ALLs in age, initial WBC count, early response to therapy, and eight-year EFS and RFS. Childhood T-ALL was associated with a worse prognosis than other sub-types of childhood ALL.</p>

Report on induction efficacy of protocol ALL-2005 and middle term follow-up of 158 cases of childhood acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To reduce the risk of infection during the induction therapy while to ensure remission rates, and to evaluate the protocol ALL-2005.</p><p><b>METHODS</b>The minimal residual disease (MRD) was detected by flow cytometry on day 35 and 55 of induction therapy. The efficacy of induction and the clinic grouping were evaluated by MRD level. From May 1, 2005 to April 30, 2007, 158 children with newly diagnosed ALL were enrolled in this study. According to clinic grouping criteria of ALL-2005, patients were stratified into 3 groups: low-risk( LR), intermediate-risk (MR) and high-risk (HR). The remission rates, therapy related complication during induction, and the relationship between MRD level on day 35 and 55 of induction and prognosis were analyzed. The endpoints are disease-free survival (DFS), relapse and death of any cause. Patients lost to follow-up were censored at the time of their withdrawal.</p><p><b>RESULTS</b>Of the 158 patients, 59 were LR, 93 MR and 6 HR. The CR rate on day 35 was 98.1%. There were detectable MRD in 139 (88.0%) patients. In 94 patients (68.6%) MRDs were < or = 0.01% on day 35 being 73.1% (49/67) for LR and 63.4% (45/71) for MR (P = 0.219). During induction therapy, 43 patients (27.2%) developed infection and among them 1.3% (2/158) suffered serious infection and 0.6% (1/158) died of complication. Four patients (2.5%) in CR were lost follow-up, 17 patients (10.8%) relapsed, including 4 patients (4.3%) with MRD < or = 0.01% and 10 (23.3%) >0.01% on day 35 (P = 0.003). One died of severe malnutrition and infection in CR. With a median follow-up of 20 (12-35) months, the estimated 30 month DFS for whole group was (81.6 +/- 4.5)% including (94.1 +/- 3.3)% for LR, (82.8 +/- 4.4)% for MR, and (91.0 +/- 5.4)% for MRD < or = 0.01%, (67.1 +/- 9.5)% for MRD >0.01% on day 35 and (89.1 +/- 5.3)% for MRD < or = 0.01% and (46.9 +/- 15.6)% for MRD >0.01% on day 55.</p><p><b>CONCLUSION</b>The risk of infection and therapy related death during induction with protocol ALL-2005 are lower, while the remission rate and quality of the induction are better. Longer follow-up is needed to estimate the long-term result.</p>

Prognostic value of early treatment response in children with acute lymphoblastic leukemia: a single institution experience in Shanghai, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Early response to therapy is one of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL). This study aimed to assess the prognostic value of morphological assessment of bone marrow blasts during remission induction and determination of minimal residual disease (MRD) after remission induction.</p><p><b>METHODS</b>From January 1998 to May 2003, 193 children with newly diagnosed ALL were enrolled on the ALL-XH-99 protocol. Blast cell count in the bone marrow was examined on day 19 of remission induction and by the completion of remission induction. MRD was measured with the flow cytometry. Event-free survival (EFS) was estimated by Kaplan-Meier analysis and the distributions of EFS were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.</p><p><b>RESULTS</b>The 4-year EFS was significantly worse in patients with > or = 5% lymphoblasts in the bone marrow on day 19 as compared to those with <5% lymphoblasts on that date (42.59%+/- 14.28% vs 74.24%+/- 6.67%; p< 0.01). The 4-year EFS was significantly worse in patients with any amount of lymphoblasts in the bone marrow on the remission date as compared to that of other patients with no morphologically identifiable blasts (63.47%+/-9.23% vs 76.41%+/- 6.09%; p<0.05). The patients with MRD <0.01 had significantly better outcome than those with a level > or = 0.01% (15-month EFS:94.44%+/-5.40% vs 23.81%+/- 20.26%; p<0.01).</p><p><b>CONCLUSIONS</b>Early treatment response as assessed by morphological examination or minimal residual leukemia determination by flow cytometry has important prognostic significance, and can be performed in a resource-poor patient population.</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>

Application of effective antigen combinations in childhood B lineage acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To probe into the occurrence rates of the effective antigen combinations which were used to detect the minimal residual disease (MRD) by flow cytometry in childhood B-lineage acute lymphoblastic leukemia (B-ALL), as well as the relationship between clinical-biologic factors and different combinations.</p><p><b>METHODS</b>Among the 327 B-ALL children enrolled in our study, 289 cases were identified with at least one antigen combination as MRD marker. Their bone marrow samples were monitored by using 9 combinations with 4 antigens each, analyzed the occurrence rates and compared them with international reports. Also the differences in the distribution of each antibody combination in the different clinical-biologic groups were compared by the chi-square test and Fisher's exact test.</p><p><b>RESULTS</b>(1) Totally 327 cases of childhood B-ALL were screened for antibody combinations of interest and 88.4 percent of them (289 cases) were identified with effective antibody combinations. (2) The occurrence frequencies of antigen combinations were different. The highest frequency was seen with TdT/CD10/CD34/CD19 combination which was 70.59 percent. Expressions of antigen combinations in Chinese children were different from those in western countries. (3) Some antibody combinations presented different frequency among different clinical groups. CD38/CD10/CD34/CD19 was expressed more often in samples of relapsed patients (P = 0.045). CD66c/CD10/CD34/CD19 expression was significantly higher in BCR/ABL positive group (P = 0.037) and relapsed patients group (P = 0.047). TdT/CD10/CD34/CD19 was expressed more in MLL-AF4 negative group (P = 0.005) and Prednisone Good Response group (P = 0.002). CD58/CD10/CD34/CD19 was correlated with low relapse rate (P = 0.032).</p><p><b>CONCLUSION</b>(1) The coverage rate of 9 antigen combinations in our study was 88.4%. The occurrences of frequency of different antibody combinations in B-ALL were different, and also different from that of western countries. The occurrence frequencies of antibody combinations CD21/CD10/CD34/CD19, CD22/CD10/CD34/CD19, CD10/CD56/CD34/-CD19 and TdT/Cu/CD34/CD19 were lower than those of the western report, while CD38/CD10/-CD34/CD19, CD45/CD19/CD10/CD34, CD58/CD10/CD34/CD19 and CD66c/CD10/CD34/CD19 were similar to those of the reports from western countries. (2) TdT/CD10/CD34/CD19 may work as a simplified method to detect MRD in Chinese population. (3) The occurrence frequency of CD38/CD10/CD34/CD19, CD45/CD19/CD10/CD34, CD58/CD10/CD34/CD19, TdT/CD10/CD34/CD19 could be effective remediation and evidence to evaluate the remission quality and guide the therapy, especially for those with no original MRD marker record. (4) CD58/CD10/CD34/CD19 and TdT/CD10/CD34/CD19 may correlate with good prognosis, but CD66c/CD10/CD34/CD19 and CD38/CD10/CD34/CD19 may predict poor prognosis. These results might contribute to individual risk evaluation and guide the therapy selection.</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>