Adolescent ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Leukemia ; drug therapy ; mortality ; therapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; therapy ; Male ; Mycophenolic Acid ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Retrospective Studies ; Treatment Outcome

Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Survivors ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo investigate the neurocognitive function of children with acute lymphoblastic leukemia (ALL) and long-term disease-free survival and related influencing factors.

METHODSA total of 40 ALL children with long-term disease-free survival were enrolled as study group, and 40 healthy children were enrolled as control group. The Chinese Wechsler Intelligence Scale for Children (C-WISC), continuous performance test (CPT), and Stroop test software were used for the evaluation of all children. Neurocognitive function was compared between groups and influencing factors were analyzed.

RESULTSCompared with the control group, the study group had significantly lower full intelligence quotient, verbal intelligence quotient, and performance intelligence quotient in C-WICS (P<0.05) and significantly higher numbers of mistakes and misses in CPT (P<0.05). There were no significant differences in the numbers of correct answers, mistakes, and misses of word-color consistency between the study group and the control group (P>0.05), while the study group had significantly higher numbers of mistakes and misses of word-color contradiction and irrelevance (P<0.05). The total dose of high-dose methotrexate and ALL risk classification were associated with the reduction in intelligence quotient, and children's younger age at diagnosis of ALL was associated with the higher numbers of misses and mistakes. Girls tended to have a significantly lower performance intelligence quotient than boys (P<0.05).

CONCLUSIONSALL children with long-term disease-free survival have neurocognitive impairment, which may be associated with the dose of chemotherapeutic drugs, age at diagnosis, and sex.

Adolescent ; Child ; Child, Preschool ; Cognition ; drug effects ; Disease-Free Survival ; Female ; Humans ; Infant ; Intelligence Tests ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; psychology

OBJECTIVETo evaluate the effectiveness and the practicability of the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 95 (ALL-BFM 95) protocol in treating childhood high-risk acute lymphoblastic leukemia (HR-ALL).

METHODSA retrospective analysis of 47 children with newly diagnosed HR-ALL between July 2003 and August 2013 was performed. These children were treated by the ALL-BFM 95 protocol. Survival was evaluated by Kaplan Meier analysis and Log-Rank test.

RESULTSRelapse-related death occurred in 12 of 47 patients (26%), and 5 of 47 patients (11%) were treatment-related mortality. Five-year probability of event-free-survival (pEFS) was 62%. Children with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than those with chemotherapy alone (77% vs 52%; P=0.035). The patients who were only poor responders to prednisone had a better outcome (5-year pEFS 80%) than the Days 15 and 33 bone marrow M3 subgroups (5-year pEFS 60% and 0 respectively).

CONCLUSIONSALL-BFM 95 protocol can improve the outcome of children with high-risk ALL. The major cause of death is attributed to relapse. Chemotherapy plus HSCT can produce a better outcome than chemotherapy alone. The Days 15 and 33 bone marrow M3 subgroups have a poor prognosis.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; Risk ; Treatment Outcome

OBJECTIVETo study the clinical features of children with relapsed acute lymphoblastic leukemia (ALL) treated with the CCLG-ALL2008 protocol.

METHODSThe data of 591 children who were newly diagnosed with ALL and were treated with the CCLG-ALL 2008 protocol between April 2008 and June 2013 were collected, and the clinical features of 80 children with relapsed ALL were retrospectively analyzed.

RESULTSAfter treatment with the CCLG-ALL2008 protocol, the recurrence rate in the standard-risk, intermediate-risk and the high-risk groups were 7.0%, 10.7% and 28.7% respectively (P<0.05). The recurrence rate in patients with TEL/AML1-positive ALL was 8.0%, and the 5-year overall survival (OS) of the relapsed patients was 37.04%. The recurrence rates in patients with MLL-positive and BCR/ABL-positive ALL were 35.0% and 24.2% respectively, and none of the relapsed patients had long-term survival. The recurrence mainly occurred at the very early stage (53%), and none of patients with recurrence at the very early stage had long-term survival. The recurrence occurred at early stage and late stage accounted for 34% and 14% respectively, and the 5-year OS rates of patients with recurrence at early stage and late stage were 11.44% and 60.00% respectively. The sites of recurrence were mainly bone marrow alone (83%), and the 5-year OS of patients with recurrence at bone marrow alone was 9.23%. The recurrence in bone marrow and outside bone marrow accounted for 11%, and the 5-year OS of patients with recurrence in both bone marrow and outside bone marrow was 25.00%. The recurrence only outside bone marrow accounted for 6%, and the 5-year OS of patients with recurrence only outside bone marrow was 100%. The recurrence rate in patients with T-cell ALL was 9.5%, and none of the relapsed patients had long-term survival. The recurrence rate in patients with B-cell ALL was 14.3%, and the 5-year OS of the relapsed patients was 15.52%.

CONCLUSIONSAfter treatment with the CCLG-ALL2008 protocol, a relatively high recurrence rate is observed in children with high-risk ALL. Positive MLL and positive BCR/ABL are high-risk factors for recurrence. The recurrence rate is not significantly correlated with immunophenotype. A very low survival rate is seen in children whose recurrence have the following features: at early stage, only in bone marrow, T-cell ALL, and abnormal BCR/ABL and MLL.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; Prognosis ; Recurrence ; Retrospective Studies

OBJECTIVETo study the efficacy and safety of Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL2008) protocol combined with tyrosine kinase inhibitor (TKI, imatinib) for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in children.

METHODSThe clinical data of 53 patients aged less than 15 years when first diagnosed with Ph+ ALL between October 2008 and December 2013 were retrospectively analyzed. The patients were assigned to two groups: HR (n=26) and HR+TKI (n=27). The HR group was treated with CCLG-ALL2008 protocol (for high-risk patients). The HR+TKI group was treated with imatinib in combination with CCLG-ALL2008 protocol (for high-risk patients).

RESULTSThe complete remission rate and chemotherapy induction-related mortality rate in the TKI+HR and HR groups were 100% vs 75% and 0 vs 15%, respectively. The 3-year event-free survival (EFS) rate in the HR group was (6±5)%; the 5-year EFS rate of the TKI+HR group was (52±11)%. Compared with the HR group, the TKI+HR group had no increase in the toxic responses to chemotherapy and had a decrease in the infection rate during the induction period.

CONCLUSIONSApplication of imatinib significantly improves the clinical efficacy in children with Ph+ ALL and has good safety.

Adolescent ; Antineoplastic Agents ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Imatinib Mesylate ; adverse effects ; therapeutic use ; Male ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; mortality ; Protein Kinase Inhibitors ; therapeutic use

OBJECTIVETo study the long-term efficacy of CAMSBDH-ALL chemotherapy protocol for the treatment of childhood acute lymphoblastic leukemia (ALL).

METHODSThree hundred and eighteen children who were newly diagnosed with ALL between January 1999 and December 2007 were enrolled in this study. Among the 318 children, 83 children who hospitalized before December 2002 were treated with CAMSBDH-ALL99 protocol, including 48 patients of standard risk and 35 patients of high risk. The patients (n=235; 131 in standard risk and 104 in high risk) who hospitalized after December 2002 were treated with CAMSBDH-ALL03 protocol. Patients in the CAMSBDH-ALL99 protocol group were treated with conventional chemotherapy. CAMSBDH-ALL03 protocol was modified based on the CAMSBDH-ALL99 protocol.

RESULTSThe long-term overall survival (OS) and event-free-survival (EFS) in the CAMSBDH-ALL03 group was significantly higher than in the CAMSBDH-ALL99 (P<0.01). The long-term OS and EFS of standard risk and high risk patients in the CAMSBDH-ALL03 protocol group were significantly higher than in the CAMSBDH-ALL99 protocol group (P<0.01). The CAMSBDH-ALL03 protocol group showed a significantly lower recurrence rate (28.9%) than in the CAMSBDH-ALL99 protocol group (50.6%) (P<0.05). The mortality rate in the CAMSBDH-ALL03 protocol group was 28.5% vs 56.6% in the CAMSBDH-ALL99 protocol group (P<0.05).

CONCLUSIONSThe therapeutic effect of the CAMSBDH-ALL03 protocol is supior to the CAMSBDH-ALL99 protocol group for childhood ALL, with a higher long-term survival rate.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Clinical Protocols ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; Recurrence

OBJECTIVETo investigate the effect of Huangqi injection on the short-term prognosis in childhood with acute lymphoblastic leukemia (ALL).

METHODSA retrospective analysis was performed on the clinical data of 105 children newly diagnosed with ALL between January 2009 and December 2012. These children were randomly divided into treatment group (18 low-risk cases, 7 medium-risk cases, and 24 high-risk cases) and control group (21 low-risk cases, 7 medium-risk cases, 28 high-risk cases). Both groups were given remission induction therapy based on the levels of risk. Throughout the remission induction therapy, the treatment group also received Huangqi injection (0.5-1.0 mL/kg per day) by intravenous infusion, while the control group was given 0.9% sodium chloride injection instead. The two groups were compared in terms of distribution of prognostic factors and complete remission (CR) rate after remission induction therapy, as well as the incidence of minimal residual disease (MDR) (≥ 10(-4) and < 10(-4)) among all patients in the two groups on day 19 of remission induction therapy and among B-ALL patients in the two groups when achieving a CR at the end of remission induction therapy.

RESULTSOf the 105 children with ALL, 99 had B-ALL, and 6 had T-ALL. There were no significant differences in the distribution of prognostic factors between the two groups (P>0.05). The overall CR rate of 105 patients was 79%; there was no significant difference in CR rate between the treatment and control groups (82% vs 77%; P>0.05); also, no significant differences were found between the two groups in the CR rates among high-, medium-, and low-risk cases (P>0.05). On day 19 of remission induction therapy, the incidence of MRD≥10(-4) in the treatment group was significantly lower than that in the control group (69% vs 95%; P<0.05); among 80 children with B-ALL who achieved a CR (43 cases in the control group and 37 cases in the treatment group), the incidence of MRD≥10-4 was significantly lower in the treatment group than in the control group (27% vs 58%; P<0.05); in both circumstances above, the high- and low-risk cases in the treatment group had a significantly lower incidence of MRD≥10(-4) than the control group (P<0.05).

CONCLUSIONSHuangqi injection combined with chemotherapy has an enhanced anti-tumor effect and can improve the short-term prognosis and clinical outcome in children with ALL.

Astragalus Plant ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Incidence ; Induction Chemotherapy ; Injections ; Male ; Neoplasm, Residual ; epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; Prognosis

Varicella-zoster virus infection can lead to severe illness in immunocompromised patients. Further the mortality rate of disseminated varicella infection is extremely high particularly in immunocompromised children. We report a case of disseminated varicella infection in a child with acute lymphoblastic leukemia who was receiving chemotherapy, but was initially admitted with only for acute abdominal pain. The patient rapidly developed severe complications, including acute respiratory distress syndrome, acute hepatitis, disseminated intravascular coagulation, and encephalopathy. Acyclovir is a highly potent inhibitor of varicella-zoster virus infection. However, owing to rapid disease progression, it might not be sufficient to control a disseminated varicella infection, especially in immunocompromised patients. Immunoglobulin neutralize virus invasion and suppress viremia, acting synergistically with acyclovir. In this case, early administration of acyclovir and a high-dose of immunoglobulin, combined with mechanical respiratory support, proved adequate for treatment of this severe illness.
Abdominal Pain ; Acyclovir ; Chickenpox* ; Child* ; Disease Progression ; Disseminated Intravascular Coagulation ; Drug Therapy ; Hepatitis ; Herpesvirus 3, Human ; Humans ; Immunocompromised Host ; Immunoglobulins* ; Mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Respiratory Distress Syndrome, Adult ; Viremia

OBJECTIVEAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, while glucocorticoid (GC) is a critical component in multi-agent chemotherapy protocols currently used for the treatment of ALL. The purpose of this study was to investigate the relationship between the glucocorticoid induction test and the clinical features and the prognosis of Chinese childhood ALL.

METHODThe study recruited 309 hospitalized patients (187 male and 122 female) with childhood ALL, the sex, age, initial WBC count, immunophenotype, chromosome and gene expression were recorded. After diagnosis, all patients received GC induction test for 7 days. Then they were divided into prednisone good response (PGR) group and prednisone poor response (PPR) group according to the peripheral lymphoblast count on D8. Early responses to chemotherapy and treatment outcomes of the patients in the two groups were also analyzed.

RESULTOf the 309 patients, 263 belonged to PGR group and 46 belonged to PPR group. Initial WBC count was higher in PPR group than in PGR group (86.30×10(9)/L vs. 30.97×10(9)/L, P < 0.01) . B lineage ALL showed more sensitive to GC than T-ALL (86.6% vs. 60%, P < 0.05). Different initial-risk-group's sensitivity to GC differed from one another (high-risk:51.4%, medium-risk: 82.7%, standard risk: 93.7%, P < 0.0125). There was no significant difference between two groups in chromosomal karyotypes (P > 0.05). BCR-ABL positive ALL showed lower sensitivity to GC (P < 0.05) , while MLL, TEL-AML1, E2A-PBX1 positive rates in two groups were of no statistical significance (P > 0.05). Bone marrow was reviewed on D15 and D33, and the CR rates in PGR group were significantly higher than that in PPR group (D15: 60.5% vs. 32.6%, D33: 94.6% vs. 73.3%, P < 0.01) ; Minimal residual disease (MRD) levels were examined on D33, W12, and both were much lower in PGR group (D33: P < 0.01, W12: P < 0.05). Of the PGR group 215 patients (81.7%) remained continuously in complete remission (CCR) while only 28 cases (60.9%) in PPR group did so. The CCR rate was much higher in PGR group than that in PPR group (P < 0.01).

CONCLUSIONClosely related to clinical features and the outcomes of treatment, GC induction test is also an important prognostic factor in Chinese childhood ALL.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; Child ; Child, Preschool ; Female ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Leukocyte Count ; Male ; Neoplasm, Residual ; drug therapy ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; genetics ; mortality ; Predictive Value of Tests ; Prognosis ; Remission Induction ; Survival Rate