[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.

[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.

[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.

Identification and Validation of Gene Expression Pattern and Signature in Patients with Immune Thrombocytopenia.

In the present study, we sought to define genes associated with immune thrombocytopenia (ITP). Microarray analysis revealed that of 1002 genes associated with ITP, 309 genes had downregulated expression and 693 genes had upregulated expression in patients with ITP. Gene set enrichment analysis revealed that 11 pathways were positively correlated to ITP, such as type I diabetes mellitus, intestinal immune network for IgA production, and oxidative phosphorylation. The messenger RNA expression levels of the indicated genes, including HLA-DRB5, IGHV3-66, IFI27, FAM212A, PLD5, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1ß, and IL-4, were significantly increased in patients with ITP compared with healthy humans, while MMP8, SLC1A3, CRISP3, THBS1, FMN1, and IL-10 were decreased. In conclusion, the gene expression profile of patients with ITP has established a foundation to study the gene mechanism of ITP progression.

Renal tumor in developing countries: 142 cases from a single institution at Shanghai, China.

BACKGROUND: The clinical management of children with renal tumors including Wilms' tumor, clear cell sarcoma, rhabdoid tumor and other renal tumors in our center was designed according to the National Wilms' Tumor Study Group protocols. METHODS: A total of 142 consecutive patients who had been diagnosed as having renal tumors at Shanghai Children's Medical Center were reviewed retrospectively in the period of December 1998 and September 2012. Diagnosis and treatment were decided by a multidisciplinary team including oncologists, surgeons, pathologists and sub-specialized radiologists. RESULTS: The median age of the patients at the time of diagnosis was 27 months. The tumor stages of the patients were as follows: stage I 24.6%, stage II 23.2%, stage III 32.3%, stage IV 14.1%, and stage V 5.6%. Favorable histology was diagnosed in 80.3%, anaplasia in 4.2%, clear cell sarcoma in 9.8%, rhabdoid tumor in 4.9%, and other renal tumors in 0.7% of the patients. The event-free and overall 5-year survival rates were 80% and 83%, respectively. Tumor relapse and progress was seen in 25 patients (17.6%). The median relapse time was 6 months (range: 2-37 months). Seven relapsing patients were retreated and four of them got second complete remission (three in stage II, one in stage I). CONCLUSION: A multi-disciplinary team work model is feasible in developing countries, and the renal tumors protocols basically from developed countries are safe in developing countries.

[Outcomes of 104 children with B-cell non-Hodgkin lymphoma].

OBJECTIVE: To analyze outcomes and prognostic factors of children with B-cell non-Hodgkin lymphoma (B-NHL). METHODS: 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. RESULTS: 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. CONCLUSION: B-NHL 2001 protocol was reasonable for B-NHL children. Higher staging, elevated LDH, serum ferritin and poor early response increased risk for recurrence.

[Long-term follow-up of childhood low-risk ALL patients treated with SCMC-ALL-2005 protocol].

OBJECTIVE: To evaluate the long-term efficacy of SCMC-ALL-2005 protocol in treatment of low-risk childhood acute lymphoblastic leukemia (ALL). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Long-term outcomes of childhood lymphoblastic lymphoma: report of 70 cases].

OBJECTIVE: To summarize long-term outcomes of childhood lymphoblastic lymphoma (LBL) with protocol CCCG-97 and -2002. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

What is the result: chylous leakage following extensive radical surgery of neuroblastoma.

BACKGROUND: Postoperative chylous leakage is a rare complication that results from disruption of either mediastinal or retroperitoneal lymphatic channels during dissection or from obstruction by original lesions such as a malignancy. There is lack of clinical experience in pediatric patients about how to manage the leakage and what the result will be. METHODS: We retrospectively analyzed the clinical outcomes of 5 children with neuroblastoma (NB) (stage 4 in 4 children and stage 1-2 in 1 child) who had received non-surgical treatment of chylothorax and/or chylous ascites after retroperitoneal/posterior mediastinal extensive radical resection of NB for complete tumor removal. Conservative therapy with low-fat diet, medium-chain triglyceride and/or total parenteral nutrition was the mainstay treatment for chylous leakage. RESULTS: Four of the 5 children recovered after 6-32 days of conservative treatment, and the last one who did not respond was cured by surgical management for chylous fistula 45 days after primary surgery. Postoperative imaging showed that more than 90% of tumors were resected and all of them showed very good partial remission (VGPR). Among the 4 patients in stage 4, 3 relapsed after radical resection of NB. The patient of stage 1-2 was still in VGPR. CONCLUSIONS: The majority of patients with chylous ascites/chylothorax after extensive radical surgery for posterior mediastinum/retroperitoneum NB could be cured by non-surgical treatment. But the final result of original disease has not been greatly changed by intensive surgery for stage 4 NB.

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

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

[Analysis of clinical outcomes of 63 children with acute monocytic leukemia].

OBJECTIVE: 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. METHOD: 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. RESULT: (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). CONCLUSION: 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.

[ALL-2005 protocol experience in the therapy of children and adolescents over 10 years of age with acute lymphoblastic leukemia].

OBJECTIVE: To explore the incidence, clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL). METHODS: 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. RESULTS: 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). CONCLUSION: 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.