The changing role of stem cell transplantation in childhood.

Over the past decade, relevant improvements and refinements have significantly changed the indications, technique and results obtained with allogeneic hematopoietic SCT (HSCT) in childhood. A fundamental turning point in the history of allogeneic HSCT is represented by the use of placental blood, which was first employed in 1988 in a patient with Fanconi anemia, successfully transplanted with cord blood cells from an HLA-identical sibling. Since then, thousands of children were given an allograft of cord blood-derived hematopoietic progenitors, mainly from an unrelated donor. This large clinical experience has documented that, as compared with BMT, cord blood transplantation (CBT) is associated with reduced incidence and severity of GvHD. The outcome of recipients given unrelated CBT has been reported to be at least as good as that of patients transplanted with either BM or peripheral blood mobilized cells of an unrelated volunteer. Another emerging strategy of HSCT is that of using HLA-partially matched relatives as donors of hematopoietic progenitors. The infusion of a huge number of positively in vitro-selected CD34+ cells, with the concomitant removal of T cells, has been demonstrated to permit sustained engraftment of donor hematopoiesis, without the occurrence of GvHD in the majority of patients transplanted from an HLA-disparate relative. In adults given this type of transplantation, the most favorable results have been reported for AMLs and when the donor displays alloreactivity of natural killer cells. It remains to be definitively proved whether these findings documented in adults maintain their value in pediatric patients transplanted from an HLA-disparate family donor. Finally, the last few years have witnessed the emergence of approaches of adoptive cell therapy aimed at optimizing the results of allograft through strategies able to reinforce immune competence against pathogens, as well as against tumor cells, or at modulating donor T-cell alloreactivity.

The immunosuppressive effect of human cytomegalovirus infection in recipients of allogeneic hematopoietic stem cell transplantation.

In immune-competent individuals, human cytomegalovirus (HCMV) infection is associated with impairment of T-cell function. Our goal was to evaluate prospectively whether clinically asymptomatic HCMV infection in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients, treated pre emptively with ganciclovir, influences T-cell function as well. Mitogen-stimulated T-cell proliferative activity, together with cell surface markers, was tested in 49 patients on days + 30, + 45, + 60, and + 90 after alloHSCT and, additionally, in cases of positive HCMV pp65-antigenemia. HCMV infection was diagnosed in 19 patients. None of them developed HCMV disease. T-cell proliferative activity was significantly decreased on days when HCMV antigenemia was positive as compared to days without antigenemia. The number of pp65-positive cells negatively correlated with proliferative response. Comparison of patients who did experience HCMV infection with those who did not reveals significant decrease of T-cell proliferative activity observed on days + 30 and + 45, a time period when antigenemia was most frequently found to be positive, whereas no difference was detected on days + 60 and + 90. We conclude that, even clinically asymptomatic, HCMV infection has negative impact on T-cell proliferation capacity in alloHSCT recipients. However, pre emptive therapy with ganciclovir makes this immunosuppressive effect transient and restricted to the time of infection duration.

[Intrauterine growth retardation: diagnostic and therapeutic approach]. / Approccio diagnostico-terapeutico al ritardo di crescita intrauterino.

Intrauterine growth retardation (IUGR) refers to the fetal growth pattern and assumes that at least 2 intrauterine growth assessments are performed, indicating a low growth velocity in the fetus. The term "small for gestational age" (SGA) does not refer to fetal growth but to the size of the infant at birth. Infants with SGA have a low weight and/or length for their gestational age at birth below the 10(th) percentile or -2 SD. Approximately 3-5% of all newborns are born SGA. The etiology of SGA/IUGR is not known. The majority (80-85%) of infants born SGA catch-up within the normal range by 2 years of age. SGA has also been associated with increased prevalence of hypertension and dyslipidaemia at a relatively young age. Most controlled trials have shown a beneficial effect of GH treatment. The growth response seems to be due to the cumulative dose received, parenteral adjusted height standard deviation score (SDS) and bone age pretreatment, baseline overnight peak of GH and IGF-I levels. During GH treatment, children born SGA show a significant increase in fasting levels of insulin and proinsulin and a decrease in insulin sensitivity. Fasting glucose levels significantly increase. All these effects are reversible upon interruption of treatment. However, fasting insulin concentrations as well as glucosylated hemoglobin must be carefully monitored during GH treatment. Total cholesterol, LDL cholesterol and the atherogenic index significantly decrease during GH treatment. An acceleration of bone maturation with GH treatment has been reported even though a gain in height SDS for bone age is demonstrated.