Immunophenotypic characteristics of juvenile myelomonocytic leukaemia and their relation with the molecular subgroups of the disease.

The diagnosis of juvenile myelomonocytic leukaemia (JMML) is based on clinical, laboratory and molecular features but immunophenotyping [multiparametric flow cytometry (MFC)] has not been used routinely. In the present study, we describe the flow cytometric features at diagnosis with special attention to the distribution of monocytic subsets and the relation between MFC and molecular subgroups. MFC was performed with an eight-colour platform based on Euroflow. We studied 33 JMML cases. CD34+ /CD117+ /CD13+ cells >2% was found in 25 cases, and 51·5% presented an aberrant expression of CD7. A decrease of CD34+ /CD19+ /CD10+ cells was seen in eight cases and in four they were absent. The granulocytic population had a decreased side scatter in 29 cases. Bone marrow monocytic precursors were increased in 28 patients, with a decrease in classical monocytes (median 80·7%) and increase in CD16+ (intermediate and non-classical). A more pronounced increase in myeloid CD34+ cells was seen in patients with Neurofibromatosis type 1 (NF1) and tyrosine-protein phosphatase non-receptor type 11 (PTPN11), with aberrant CD7 expression in four of six and 10/12 patients respectively. Thus, JMML shows an immunophenotypic profile similar to myelodysplastic syndromes, and a different monocyte subset distribution when compared with chronic MML. MFC proved to be an important diagnostic tool that can help in differential diagnosis with other clonal diseases with monocytosis.

Visfatin is a positive predictor of bone mineral density in young survivors of acute lymphocytic leukemia.

Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.

Subcutaneous adipose tissue plays a beneficial effect on subclinical atherosclerosis in young survivors of acute lymphocytic leukemia.

PURPOSE: The aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: This cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis. RESULTS: Treatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (P<0.050). In a multiple linear regression model, cIMT positively correlated with exposure to CRT (P=0.029), diastolic BP (P=0.016), and leptin-to-adiponectin ratio (P=0.048), while negatively related to SAT (P=0.007). CONCLUSION: In young survivors of childhood ALL, CRT modified the distribution of fat and played a critical role in determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease might be attenuated by SAT. Changes in body fat must be evaluated in this group of patients in the early course of survivorship in order to avoid premature cardiovascular disease associated with atherosclerosis. Yet, further research as regards the possible protective effect of SAT on vascular disease is warranted.

Leukemia, non-Hodgkin's lymphoma, and Wilms tumor in childhood: the role of birth weight.

There is emerging evidence that higher birth weight is associated with increased risk of cancer, in particular childhood leukemia. The purpose of this paper is to study whether this correlation is also significant with other childhood cancer. For this, we conducted a case-control study including 410 childhood cancer patients and 1,575 matched controls to investigate birth weight as a risk factor for leukemia, Wilms tumor, and non-Hodgkin's lymphoma. The estimated risk for all cancers has been found to be statistically and significantly higher in birth weight of more than 4,000 g (odds ratio, 2.50 and 95% confidence intervals (CI), 1.72-3.63). For leukemia, the estimated risk was 1.86 (95% CI, 1.04-3.30), for non-Hodgkin lymphoma, 1.99 (95% CI, 1.08-3.69), and being more remarkable for Wilms tumor, 4.76 (95% CI, 2.73-8.28). Moreover, moderate increased risk of both leukemia and non-Hodgkin lymphoma was also associated with birth weight between 3,000 and 3,999 g. High birth weight was associated with all cancers also when adjusted by gestational age, length at birth, and gender (odds ratio, 6.10 and 95% CI, 1.15-32.57). No associations were found for maternal alcohol consumption during pregnancy, maternal smoking, or smoking by other people at home or presence of obstetric variables (e.g., gestational diabetes, preeclampsia, and abruptio placentae). The present study supports the hypothesis that high birth weight is an independent risk factor for childhood Wilms tumor, leukemia, and non-Hodgkin lymphoma. Further studies should explore biological reasons to explain this relationship and, ultimately, to expand our knowledge about prenatal influences on the occurrence of this disease.

Cefepime monotherapy is as effective as ceftriaxone plus amikacin in pediatric patients with cancer and high-risk febrile neutropenia in a randomized comparison.

BACKGROUND AND PURPOSE: The empirical use of antibiotic therapy is widely accepted for patients with fever and neutropenia during cancer chemotherapy. The use of intravenous monotherapy with broad-spectrum antibiotics in patients at high risk for complications is an appropriate alternative. However, few data are available for pediatric patients. The aim of this study was to compare the efficacy and safety of cefepime (CFP) monotherapy with ceftriaxone plus amikacin (CFT+AK) in children and adolescents with febrile neutropenia (FN). METHODS: A prospective randomized open study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy was conducted. Patients were randomized to receive CFP or CFT+AK. The randomization was based on number lists. RESULTS: Fifty seven patients with 125 episodes of fever and neutropenia were evaluated (CFP, 62 episodes; CFT+AK, 63 episodes). The mean neutrophil count at admission to hospital was 118.6 cells/mm(3) for patients in the CFP group and 107 cells/mm(3) for patients in the CFT+AK group. The mean duration of neutropenia was 9 days for the CFP group and 8 days for the CFT+AK group. Analysis of only the first episodes for each patient showed that CFP treatment was successful for 65.5% of episodes and CFT+AK was successful for 64.3% of episodes. The overall rates of success with modification were 90% for the CFP group and 89% for the CFT+AK group. No major treatment-emergent toxicity was reported. CONCLUSION: Monotherapy with CFP seems to be as effective and safe as CFT+AK for initial empirical therapy in children and adolescents with FN.

Leptin assessment in acute lymphocytic leukemia survivors: role of cranial radiotherapy?

Leptin has been hypothesized to play a role in the development of obesity in leukemia survivors, particularly those who have received cranial radiotherapy. This cross-sectional study evaluated the relationship between leptin levels and body mass index (BMI) in a sample of 26 acute lymphocytic leukemia survivors of both sexes, treated with and without cranial irradiation, aged 7.6 to 17 years, at a mean 3.4+/-2.0 years off treatment. There were significantly more males among the irradiated group (P<0.001), even though no differences were encountered in pubertal stage (P=1.000), BMI standard deviation score (mean+/-SD) (0.68+/-1.00 vs. 1.19+/-0.78; P=0.164), or leptin concentrations (17.01+/-17.04 vs. 23.3+/-13.4; P=0.309). Nonetheless, there was a positive correlation between the natural logarithm of leptin and BMI standard deviation score [t(22)=2.348, P=0.028], however, no differences were recorded among irradiated and nonirradiated patients [F(2,22)=0.384, P=0.685]. When this relationship was compared between sexes, a significant difference was encountered [F(2,22)=4.907, P=0.017], with males having the strongest association (R(2)males=65.5%, R(2)females=34.7%). Leptin is a reliable adiposity index as it strongly correlates with BMI. Overall, the current data suggest that cranial irradiation did not play a role upon this relationship; however, sex differences influenced positively this correlation.

Myelodysplastic syndrome in childhood: report of two cases with deletion of chromosome 4 and the Philadelphia chromosome.

We report two pediatric patients with unclassified myelodysplastic syndrome (MDS) by the French-American-British (FAB) group. Both cases had clinical and hematological peculiarities, which had not been described yet. The cytogenetic alterations were 4q deletion and the Philadelphia (Ph) chromosome which appeared at different moments of the disease. One patient showed the Ph chromosome at disease transformation and the other at diagnosis. The different breakpoints at 4q and the presence of Ph could be a marker of this form of MDS. The association of clinical and hematological findings suggests the possibility of a new group of pediatric MDS.