[Influence of pre-pregnancy parental body mass index, maternal weight gain during pregnancy, and their interaction on neonatal birth weight].

OBJECTIVE: To investigate the influence of pre-pregnancy parental body mass index (BMI), maternal weight gain during pregnancy, and their interaction on neonatal birth weight. METHODS: A total of 1 127 pregnant women who underwent regular prenatal examinations and full-term singleton delivery in the First Hospital of Xi'an Jiaotong University from January 2017 to October 2018 were enrolled. The data on their pre-pregnancy BMI, maternal weight gain during pregnancy, pre-pregnancy BMI of the husband, and neonatal birth weight were collected. The interaction between pre-pregnancy parental BMI and maternal weight gain during pregnancy was analyzed, and their correlation with neonatal birth weight was analyzed. RESULTS: Among the 1 127 full-term neonates, the detection rates of low birth weight neonates and macrosomia were 2.22% (25/1 127) and 3.82% (43/1 127) respectively. There were significant differences in pre-pregnancy parental BMI and maternal weight gain during pregnancy among the low birth weight, normal birth weight, and macrosomia groups (P<0.05). Neonatal birth weight was positively correlated with pre-pregnancy parental BMI and maternal weight gain during pregnancy (r=0.097-0.322, P<0.05). Low maternal weight before pregnancy increased the risk of low birth weight (RR=4.17, 95%CI: 1.86-9.38), and maternal overweight/obesity before pregnancy (RR=3.59, 95%CI: 1.93-6.67) and excessive weight gain during pregnancy (RR=3.21, 95%CI: 1.39-7.37) increased the risk of macrosomia. No interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy was observed. CONCLUSIONS: Pre-pregnancy parental BMI and maternal weight gain during pregnancy are related to neonatal birth weight, and there is no interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy.

Overweight, Obesity, and Risk of Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to quantify the relationship between categories of body mass index (BMI) and age-related macular degeneration (AMD) risk in different stages. METHODS: MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between BMI and incident early or late AMD. The analyses were based on data extracted from study reports. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of this association, and dose-response relationship was assessed by restricted cubic spline. RESULTS: Seven prospective cohort studies with 1613 cases identified among 31,151 subjects were included. For overweight, the relationship remained insignificant for its association with both early AMD (RR = 0.92, 95% CI: 0.68-1.15; P = 0.54) and late AMD (RR = 1.09, 95% CI: 0.93-1.25; P = 0.18). A marked 32% increase in the risk of developing late AMD was noted among obese individuals (RR = 1.32, 95% CI: 1.11-1.53, P < 0.01), while obesity showed no significant association with early AMD (RR = 0.91, 95% CI: 0.74-1.08; P = 0.67). Furthermore, elevated BMI showed a linear dose-response relation with AMD risk (Pnonlinearity = 0.17), and the AMD risk increased by 2% (RR = 1.02, 95% CI: 1.01-1.04) for each 1 kg/m2 increase in BMI within the overweight and obese BMI ranges. CONCLUSIONS: Excess body weight was weakly associated with increase in the risk of AMD in a dose-dependent fashion, especially for its late stage, indicating that keeping normal body weight and avoiding further weight gain may confer potential protection against this disease.

[Relationship between immunological characteristics and prognosis in children with acute myeloid leukemia].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Tandem application of flow cytometry and polymerase chain reaction for choice targets of minimal residual disease in childhood acute lymphoblastic leukemia].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

[Prognostic value of early treatment response in children with acute lymphoblastic leukemia: a single institution experience in Shanghai, China].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Single nucleotide polymorphism in the promoter region of asparagine synthetase and its impact on the gene expression].

High expression of cellular asparagine synthetase (AS) is a causative factor for the resistance of leukemic cell to L-asparaginase therapy. This study was aimed to find single nucleotide polymorphism (SNPs) in the promotor region of asparagine synthetase (AS) gene and to determine if these SNPs have influence on the transcriptional activity of AS promotor. The DNA sequences of AS promoter (pAS) from 82 leukemic children and 45 controls were determined to screen for SNPs in this region and the AS mRNA level in these samples was quantified using real-time PCR assay. The results indicated that three SNPs were found in the sequenced pAS fragment. They were -239C/T, -92G/A and -62A/T respectively. The frequency of -92A allele was higher in leukemic samples than that in nonleukemic control (P<0.05). The gene expression level differed among the individuals with genotype of the -92G/A SNP, and the descending order was as follows: GA heterozygote > AA homozygote > GG homozygote. It is concluded that some features in leukemia might associate with SNP on -92A locus, and this SNP in pAS can be one of the factors influencing transcriptional activity of AS gene. The existence of the -92A allele variant contributes to a high expression of AS gene.

[Prognostic value of early treatment response in children with acute myeloid leukemia].

OBJECTIVE: To assess the prognostic value of early treatment response in children with acute myeloid leukemia (AML). METHODS: Sixty-one children with AML, 37 male and 24 female, aged 96 months (6 - 154 months), underwent treatment according to the protocol AML-XH-99 with a total treatment course of 15 months and were followed up for 12 months (1 - 74 months). Bone marrow smear was made 48 hours after the end of the first course of induction treatment. Then the children were divided into 2 groups according to the number of bone marrow blast cells: group with the number of blast cells > or = 0.15 and group with the number of blast cells < 0.15. Second bone marrow smear was made when complete remission was achieved after the end of the treatment course. Then the children were divided into 2 groups according to the number of bone marrow blast cells: group with the number of blast cells of 0.00 and group with the number of blast cells between 0.00 and 0.05. The probability of event-free survival (EFS) was estimated by Kaplan-Meier analysis. Log-rank test was used to compare the 5-year EFS (pEFS) of different groups. The differences in the biological features were compared by Chi-square analysis or Fisher exact test. RESULTS: The pEFS of the group with the number of blast cells > or = 0.15 was 18% +/- 15%, significantly shorter than that of the group with the number of blast cells < 0.15 (49% +/- 11%, P = 0.079). The 3 patients without morphologically identifiable blast all survived 5 years after complete remission had been achieved, and the pEFS of the 39 patients with the number of blast cells between 0.00 and 0.05 was 53% +/- 10%. The pEFS of the patients among which complete remission was achieved after the first course of treatment (n = 39) was 54% +/- 10%, significantly higher than that of the patients without complete remission after the first course of treatment (10% +/- 9%, P = 0.0002). Multiple factor analysis showed that achievement of complete remission after the first course of treatment and existence of central nervous system leukemia were both independent prognostic factors with the hazard ratios of 4.007 and 7.050 respectively and the 95% confidential intervals of 1.019 to 6.163 and 0.018 to 0.547 respectively (P = 0.045 and P = 0.008). The number of blasts 48 hours after the end of the first course of induction treatment was highly correlated with the rate of complete remission after the first treatment course (P = 0.000 028 8). CONCLUSION: With important prognostic significance, early treatment response, such as the number of blasts 48 hours after the end of the first course of induction treatment can predict whether complete remission can be achieved.

[Correlation between karyotypic characteristics and treatment outcome in childhood acute lymphoblastic leukemia].

OBJECTIVE: To analyze the relationship between karyotypic characteristics and treatment outcome of childhood acute lymphoblastic leukemia (ALL) and compare the difference in karyotypic aberration between ALL patients in China and in western countries. METHODS: From January 1998 to May 2003, 193 patients with newly diagnosed ALL were enrolled on protocol ALL-XH-99. The patients were classified into 4 groups according to the karyotype of the leukemia cells: normal karyotype, hypodiploid, hyperdiploid and pseudodiploid. 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. RESULTS: (1) Of 193 ALL patients, 115 had cytogenetic data. There were 53 (46.09%) with normal karyotype, 29 (25.22%) hyperdiploid, 9 (7.83%) hypodiploid, 4 coexpression of hypodiploid/hyperdiploid and 20 (17.39%) pseudodiploid. The probability of 5-year EFS for the four subgroups were (78.28 +/- 6.34)%, (86.07 +/- 6.47)%, (53.85 +/- 13.83)% and (40.10 +/- 12.17)%, respectively (P = 0.0041). (2) The clinical presentation and early response to treatment had no difference among the four groups, but the events are significantly different. (3) The probability of 5-year EFS for the combined hypodiploid group and the non-hypodiploid group was (53.85 +/- 13.83)% and (69.98 +/- 5.94)%, respectively (P = 0.1281). (4) The probability of 4-year EFS was significantly worse for patients with Philadelphia chromosome than for no Philadelphia chromosome patients [(28.57 +/- 17.07)% vs (70.85 +/- 5.60)%, P = 0.0009]. (5) Multivariate analysis suggested that the karyotypic characteristics, Philadelphia chromosome, age < 1-year or > 12-year, and white blood cell counts were independent prognostic factors. CONCLUSIONS: The cytogenetic pattern of Chinese childhood ALL patients was similar to that of western countries. Cytogenetic findings especially Philadelphia chromosome had important prognostic significance.

[Analysis of prognostic variables in childhood acute myeloid leukemia].

OBJECTIVE: To assess the prognostic value of the biological features and therapy-related factors in childhood acute myeloid leukemia (AML). METHODS: From January 1998 to May 2003, 75 patients with newly diagnosed AML were enrolled on the protocol AML-XH-99. Biological features at presentation [gender, age, white blood cells, platelet count, French-American-British (FAB) subtypes, cytogenetic abnormalities] and therapy-related factors [bone marrow (BM) blast cell counts at 48 h after the first induction course, complete remission (CR) rate after the first course of induction therapy] were analyzed. The probability of event-free survival (pEFS) was estimated by Kaplan-Meier analysis and the distributions of pEFS were compared using log-rank test. Chi-square analysis or Fisher exact test was used to compare differences in the distribution of presenting biological features. A Cox proportional hazards model was used to identify independent prognostic factors. RESULTS: (1) Univariate analysis of the proportion of patients attaining CR after induction indicate that FAB M(5), BM blasts >or= 0.150 at 48 h after the first induction course and no response to the first induction course were associated with lower CR rates (P = 0.001, 0.011, 0.000 respectively). Univariate analysis also demonstrated that the 5-year pEFS for patients with age < 1 year or > 10 years, platelet count < 20 x 10(9)/L, FAB M(5), hepatomegaly, BM blasts >or= 0.150 at 48 h after the first induction course and no response to the first induction course, central nervous system (CNS) leukemia was unfavorable, while the outcome of patients with cytogenetic abnormalities of t (8; 21) or t (15; 17) were better. (2) Multivariate analysis suggested that cytogenetic abnormality of t (15; 17), achieved CR after the first induction course and no CNS leukemia were independent favorable prognostic factors. CONCLUSIONS: Combined analysis of cytogenetic abnormalities with early treatment response has an important prognostic significance, and can predict outcomes.

[Prognostic value of minimal residual disease in childhood B-cell acute lymphoblastic leukemia].

OBJECTIVE: To assess the prognostic value of minimal residual disease (MRD) in childhood B-cell acute lymphoblastic leukemia (ALL) after induction chemotherapy. METHODS: From September 2001 to October 2004, 102 patients with newly diagnosed B-ALL were enrolled in protocol ALL-XH-99. MRD after induction therapy, before high-dose methotrexate and early intensification as well as at 1 year and 2 year maintenance therapy was detected by multiparameter-flow-cytometry (MP-FCM). RESULTS: (1) The probability of 39-month event-free survival (EFS) for patients with a level of MRD < 10(-4), was significantly higher than for those with a higher MRD [(83.00 +/- 9.90)% vs 0.00%, P < 0.01]. (2) Univariate analysis indicated that the MRD level at achieving complete remission (CR) had no relationship with the biologic features at presentation (gender, age, white blood cells and cytogenetic abnormalities), but did with Philadelphia chromosome, the time reaching CR, ALL-XH-99 risk group and lymphoblasts in bone marrow on day 19 after induction therapy (P < 0.05). (3) Multivariate analysis suggested that MRD level after the first induction course was an independent prognostic factor (hazard ratio, 5.381; 95% CI 0.004 to 0.624; P < 0.05). CONCLUSION: The MRD level at achieving CR is one of important prognostic factor in the treatment of childhood B-cell ALL, and might be used to assess the early treatment response.

[Expression of the transcription factor PAX5 in childhood acute leukemic cells].

To investigate transcription factor PAX5 expression characteristics in childhood acute leukemic cells, expression levels of PAX5 and CD19 mRNA in 6 hematological tumor cell lines and bone marrow cells of 6 normal children, 58 de novo patients and 4 relapse acute leukemic children, including 39 cases of B-ALL, 10 cases of T-ALL and 13 cases of AML, were detected by a real-time RT-PCR. The results showed that PAX5 and CD19 mRNA expression levels were 2.35% and 2.52% in Namalwa (B-cell lines) respectively, but almost not detectable in other T- and myeloid cell lines. Among clinical samples, expression of PAX5 mRNA in B-ALL was significantly higher than that in T-ALL and AML (P = 0.029 and P = 0.013 respectively). PAX5 expression was significantly lower in T-ALL and AML than that in normal controls. The difference of PAX5 mRNA expression levels between T-ALL and AML was not significant. Individual difference of PAX5 mRNA expression levels in children with B-ALL was great. Moreover, PAX5 mRNA expressions in de novo and relapse patients with B-ALL were significantly higher than those in remission (P = 0.011 and P = 0.006 respectively). As binding sites for B-cell specific activator protein have been identified in the promoter regions of CD19, the study found that in B-ALL, there was clear correlation between the expression levels of PAX5 and CD19, which was also studied by real-time RT-PCR. It is concluded that PAX5 transcripts are readily detectable and quantifiable in clinical materials with B-ALL by real-time RT-PCR. The strong PAX5 mRNA expression in some B-ALL can be considered to be particularly interesting for further analysis.

[Prognostic value of both detection of lymphoblasts in the period of early treatment and minimal residual disease in childhood acute lymphoblastic leukemia].

OBJECTIVE: To assess the prognostic value of both morphological persistent disease on day 19, on complete remission (CR) and minimal residual disease (MRD) in the bone marrow (BM) after multiagent remission induction therapy. METHODS: From January 1998 to May 2003, 193 patients with newly diagnosed ALL were enrolled on protocol of ALL-XH-99. BM blast counts on day 19 and on CR after induction therapy were examined. BM MRD at the end of induction therapy was detected by MP-FCM. RESULTS: (1) The probability of 5-year event-free survival (pEFS) was significantly worse for patients with > or = 0.050 BM lymphoblasts on day 19 than that with < 0.050 BM lymphoblasts [(42.59 +/- 14.28)% vs (74.24 +/- 6.67)%, P < 0.001]. (2) The 5-year pEFS was significantly worse for patients with a low percentage of lymphoblasts (< 0.050) in BM on CR as compared to those with no morphological persistent lymphoblasts [(63.47 +/- 9.23)% vs (76.41 +/- 6.09)%, P < 0.05]. (3) No significant difference was found in BM lymphoblasts between patients with MRD (> or = 10(-4) of nucleated bone marrow cells) and those without MRD (< 10(-4)) at the end of induction therapy (P > 0.05). The 22-month pEFS was significantly worse for patients with MRD as compared with those without MRD on CR [(23.81 +/- 20.26)% vs (94.44 +/- 5.40)%, P = 0.001]. CONCLUSIONS: BM lymphoblast > or = 0.050 on day 19 after induction therapy is an independent prognostic factor for childhood ALL; low percentage of lymphoblasts and minimal residual disease in BM on remission also do it. Patients with > or = 0.050 lymphoblast in BM on day 19 or with MRD > or = 10(-4) at the end of induction therapy should receive altered and more intensive chemotherapy.