Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 Trial.

PURPOSE: The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated. PATIENTS AND METHODS: We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR. RESULTS: The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84). CONCLUSION: The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].

A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up.

Comparative clinical studies of children and adults with immune thrombocytopenia (ITP) are poorly covered in the literature. However, the accepted classification of ITP-childhood ITP and adult ITP-results in considerable differences in treatment protocols and practice guidelines. The analysis of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) of patients at first presentation demonstrated fewer differences in clinical and laboratory findings at initial diagnosis between children and adults than expected. The present report of 2-year follow-up data supports the hypothesis that there are common aspects of childhood and adult ITP. Data of 3360 children and 420 adults were collected during the time of 2004 until 2015 at initial diagnosis. Follow-up information was available for 51% and 33% of children and 66% and 49% of adults at 12- and 24-months, respectively. Similarities were found in unexpected areas of ITP, such as the rate of late remission at 12 and 24 months, reported bleeding sites, platelet count in bleeders, and the frequency of treated patients with persistent or chronic ITP. Differences were confirmed for the overall rate of remission and treatment modalities. Unexpected differences were found in the percentage of nonbleeders, with more adults in the nonbleeder group. More studies are needed to investigate different age groups with the aim to optimize their management.

Polymorphisms in TNF and IFNG are associated with clinical characteristics of aplastic anemia in Argentinean population.

The impaired hematopoiesis in acquired aplastic anemia (AA) results from immune-mediated mechanisms. We characterized polymorphisms implicated in controlling type-1 cytokine production in 69 patients with AA. Our data suggest that the studied polymorphisms are not associated with susceptibility in the overall AA population. However, the presence of the higher expressing TNF - 308A allele was associated with younger age (p = 0.0297) and more profound neutropenia (p = 0.0312), and over-represented in patients with very severe AA (p = 0.0168). The higher producing IFNG 12 CA-repeat allele showed strong linkage disequilibrium with the + 874T allele, and was associated with a lower hemoglobin level (p = 0.0351). Also, the presence of at least one higher expressing variant was more frequent among patients responding to immunosuppressive treatment (p = 0.0519). Our findings suggest that the presence of higher expressing variants of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in AA patient genotypes could be related to clinical parameters, disease severity and therapy outcomes.

A prospective study to assess the predictive value for hereditary spherocytosis using five laboratory tests (cryohemolysis test, eosin-5'-maleimide flow cytometry, osmotic fragility test, autohemolysis test, and SDS-PAGE) on 50 hereditary spherocytosis families in Argentina.

This prospective study was carried out to assess the usefulness of five laboratory tests in the diagnosis of hereditary spherocytosis (HS), based on the correlation of erythrocyte membrane protein defects with clinical and laboratory features, and also to determine the membrane protein deficiencies detected in Argentina. Of 116 patients and their family members tested, 62 of them were diagnosed to have HS. The specificity of cryohemolysis (CH) test was 95.2%, and its cut-off value to distinguish HS from normal was 2.8%. For flow cytometry, cut-off points of 17% for mean channel fluorescence (MCF) decrease and 14% coefficient of variation (CV) increase showed 95.9% and 92.2% specificity, respectively. Both tests showed the highest percentages of positive results for diagnosis. Either CH or flow cytometry was positive in 93.5% of patients. In eight patients, flow cytometry was positive only through CV increase. Protein defects were detected in 72.3% of patients; ankyrin and spectrin were the most frequently found deficiencies. The CV of the fluorescence showed significantly higher increases in moderate and severe anemia than in mild anemia (p = 0.003). Severity of anemia showed no other correlation with tests results, type of deficient protein, inheritance pattern, or neonatal jaundice. CH and flow cytometry are easy methods with the highest diagnostic accuracy. Simultaneous reading of mean channel fluorescence (MCF) decrease and CV increase improve diagnostic usefulness of flow cytometry. This test seems to be a reliable predictor of severity. The type of detected protein deficiency has no predictive value for outcome. Predominant ankyrin and spectrin deficiencies agree with reports from other Latin American countries.

Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina.

BACKGROUND: Demographics, outcome, and management of idiopathic thrombocytopenic purpura (ITP) in children present differences between countries. Although several factors influence outcome, it is impossible to predict at diagnosis which patients will have acute or chronic disease. High rates of spontaneous remission in chronic ITP have been reported. PROCEDURE: Data concerning 1,683 patients with ITP diagnosed from 1981 to date are presented; outcome was evaluated in 1,418 children. RESULTS: Remarkable presenting features were an incidence peak in the first 2 years of age and male predominance in patients <24 months of age. Three age groups with different recovery rates (P < 0.001) were established (2-12 months: 89.8%; 1-8 years: 71.3%; 9-18 years: 49.0%). Platelet count <10 x 10(9)/L and history of previous illness were associated with higher remission rates only in patients >12 months of age. The score developed by the NOPHO Group showed a predictive value of 83.9% for acute ITP. Spontaneous remission between 6 months and 11 years from diagnosis was achieved by 107 of 325 (32.9%) non-splenectomized children with chronic ITP, and in 44.9% of them between 6 and 12 months from diagnosis. CONCLUSIONS: Age and score were main prognostic factors. Infants <1 year of age are a special group with a brief course and very high recovery rate that are not influenced by other prognostic factors. Definition of groups based on age and scoring could be useful to establish differential management guidelines. The cut-off value to define chronic ITP should be changed to 12 months.