Is FLT3 internal tandem duplication an unfavorable risk factor for high risk children with acute myeloid leukemia? : Polish experience

According to the AML-BFM 2004 Interim, a treatment protocol used in Poland since 2005, presence of FLT3 internal tandem duplication (FLT3/ITD) qualifies a patient with acute myeloid leukemia (AML) to a high-risk group (HRG). The present study was aimed to identify the prevalence of FLT3/ITD in children with AML in Poland and to evaluate its prognostic significance in the HRG patients. Out of 291 children with de novo AML treated in 14 Polish centers between January 2006 and December 2012, samples from 174 patients were available for FLT3/ITD analysis. Among study patients 108 children (61.7%) were qualified to HRG. Genomic DNA samples from bone marrow were tested for identification of FLT3/ITD mutation by PCR amplification of exon 14 and 15 of FLT3 gene. Clinical features and treatment outcome in patients with and without FLT3/ITD were analyzed in the study. The FLT3/ITD was found in 14 (12.9%) of 108 HRG children. There were no significant differences between children with and without FLT3/ITD in age and FAB distribution. The white blood cells count in peripheral blood at diagnosis was significantly higher (p <0.01) in the children with FLT3/ITD. Over 5-year overall survival rate for FLT3/ITD positive children was worse (42.4%) comparing to FLT3/ITD negative children (58.9%), but the statistical difference was not significant. However, over 5-year survivals free from treatment failures were similar. The FLT3/ITD rate (12.9%) observed in the study corresponded to the published data. There was no significant impact of FLT3/ITD mutation on survival rates, although further studies are needed on this subject

CD4+CD25highCD127low/−FoxP3+ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report

CD4+CD25highCD127low/−FoxP3+ regulatory T cells (Tregs) are currently under extensive investigation in childhood acute lymphoblastic leukemia (ALL) and in other human cancers. Usually, Treg cells maintain the immune cell homeostasis. This small subset of T cells has been, in fact, considered to be involved in the pathogenesis of autoimmune diseases and progression of acute and chronic leukemias. However, whether Treg dysregulation in CLL and ALL plays a key role or it rather represents a simple epiphenomenon is still a matter of debate. Treg cells have been proposed as a prognostic indicator of the clinical course of the disease and might also be used for targeted immune therapy. Our study revealed statistically higher percentage of Treg cells in the bone marrow than in peripheral blood in the group of 42 children with acute lymphoblastic leukemia. By analyzing Treg subpopulations, it was shown that only memory Tregs in contact with leukemic antigens showed statistically significant differences. We noticed a low negative correlation between Treg cells in the bone marrow and the percentage of blasts (R=−0.36) as well as a moderate correlation between Treg cells in the bone marrow and Hb level (R=+0.41) in peripheral blood before therapy. The number of peripheral blood blasts on day 8th correlates negatively (R=−0.36) with Tregs. Furthermore, statistical analysis revealed low negative correlation between the number of Tregs in the bone marrow and the minimal residual disease measured on day 15th, the percentage of blasts in the bone marrow and leukocytosis after 15 days of chemotherapy. These results indicate the influence of Tregs on the final therapeutic effect

Erratum: Renal Function and Solitary Kidney Disease: Wilms Tumour Survivors versus Patients with Unilateral Renal Agenesis

<i>Aims:</i> To test the hypothesis that Wilms tumour survivors (WTs) experience increased disturbance in renal function, even after prompt treatment, compared to patients with unilateral renal agenesis (URA). <i>Methods:</i> To assess the renal function of 30 WTs and 17 individuals with URA, the estimated glomerular filtration rate (eGFR) was calculated using the Schwartz and Filler formulas as well as the new Schwartz equation for chronic kidney disease. To measure kidney damage, serum levels and urine excretion of β₂-microglobulin (B2M), cystatin C (Cys C), neutrophil gelatinase-associated lipocalin (NGAL) were tested, N-acetyl-β-glucosaminidase (NAG), and albumin urine excretion and urine sediment were examined. Blood pressure was measured. <i>Results:</i> No differences were found between the groups in terms of eGFR, serum Cys C, B2M and NGAL concentrations. The urine excretion of Cys C, NGAL and NAG was similar in both groups. URA patients had higher B2M excretion than WTs. Arterial hypertension was present in 7/30 (23%) WTs and 1/17 (6%) patients with URA. <i>Conclusions:</i> WTs have similar eGFR to individuals with URA and are more likely to have arterial hypertension. The patients with URA have signs of tubular damage. This study demonstrates the need for nephrological monitoring of individuals with a single kidney