HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: clinical outcome and analysis of hematopoietic recovery.

Growing attention has been focused on cord blood as a source of transplantable hematopoietic stem cells. However, clinical experience is rather limited. In this study we describe a child with advanced acute lymphoblastic leukemia who received an HLA-haploidentical cord blood transplant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg and 0.25 x 10(4) CFU-GM/kg, were infused. Cyclosporine and prednisone were administered for graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white blood cells and granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte count > 0.5 x 10(9)/l by day +41. The presence of donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HLA phenotyping and DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoietic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The chimerism was complete and no host-derived cells could be detected. However, the engraftment was restricted to the myeloid lineage whereas lymphoid and megakaryocytic engraftments were inadequate. The immunophenotype of the patient's peripheral blood showed the presence of T lymphocytes expressing an immature phenotype (CD2+ CD3-) at day +21.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bacterial meningitis. Study from 1970 to 1988 at the Regina Margherita Children's Hospital in Turin]. / Le meningiti batteriche. Indagine dal 1970 al 1988 presso l'Ospedale Infantile Regina Margherita di Torino.

From 1970 to 1988, 330 cases of bacterial meningitis were diagnosed at the Children's Hospital Regina Margherita of Turin. Neisseria meningitidis was the most frequent cause of bacterial meningitis (45%); meningitis caused by Haemophilus influenzae increased from 4% in 1970-1983 to 19% in 1984-1988, and meningitis with pathogen unknown decreased from 28% in 1970-1983 to 7% in 1984-1988. The neonatal meningitis in 1984-1988 were caused by Streptococcus B in 90% of cases.

Immune responses by cord blood cells.

In the present study, the biological properties of cord blood cells were investigated. Cord blood mononuclear cells and T cells responded normally to activation by alloantigens in primary mixed leukocyte reactions (MLRs), indicating that cord blood T cells can be normally activated via their TcR and have normal proliferative capacities. In addition, they expressed normal levels of accessory molecules such as CD28 and LFA-1, which contribute to amplify their responses. In contrast, cord blood mononuclear cells, but not cord blood monocytes, had a reduced capacity to stimulate allogeneic cells in primary MLRs. In addition, cord blood monocytes express lower levels of HLA-DR and ICAM-1 compared to adult peripheral blood monocytes. Cord blood mononuclear cells were also impaired in their capacity to generate allogeneic cytotoxic activity in primary mixed leukocyte cultures (MLCs). In contrast, cord blood B cells were similar to adult B cells in their capacity to switch to immunoglobulin E producing cells when incubated with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody. We also demonstrated that IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) production by activated cord blood mononuclear cells was comparable to that observed with peripheral blood mononuclear cells isolated from normal adult donors. In contrast, interferon-gamma (IFN-gamma) was significantly decreased, whereas IL-4 and IL-5 were absent. Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were in general higher in the supernatants of cord blood cells. Thus, cord blood immune responses differ from those of peripheral blood at several levels. Whether these differences account for a reduced capacity of transplanted cord blood cells to modulate graft vs. host disease remains to be determined.

Reduced immunoglobulin kappa/lambda light chain ratio in perinatally HIV-1-infected children.

In 27 perinatally human immunodeficiency virus type 1 (HIV-1)-infected children, we measured, by immunonephelometry, the kappa/lambda light chain ratio (KLR) of serum immunoglobulins. The latter is a recently available laboratory index reflecting the balance between the synthesis of K isotypes and L isotypes. KLR was consistent over time in each subject, and was significantly lower than that of an age-matched normal population, independently of disease status and therapy. These data indicate a bias, in these subjects, to produce preferentially lambda rather than kappa light chains, contributing to the multiple B-cell abnormalities in HIV-1-infected children.

Immune functions of cord blood cells before and after transplantation.

There have been numerous reports of decreased acute and chronic graft-versus-host disease in patients receiving HLA-matched or HLA-disparate umbilical cord transplants. It has been proposed that this may be due to the unique properties of the neonatal immune system, which permit the development of tolerance to alloantigens. This review discusses experimental evidence contrasting the immune functions of cells derived from cord blood and those from peripheral blood.

Growth impairment, IGF I hyposecretion and thyroid dysfunction in children with perinatal HIV-1 infection.

We evaluated the growth pattern, bone age, insulin-like growth factor I (IGF I) secretion and thyroid function in 24 perinatally infected children: 9 asymptomatic or paucisymptomatic (group 1) and 15 with a more advanced disease state and treated with zidovudine (group 2). Statural and ponderal growth were compared with those of 37 at-risk children who seroreverted. During the two-year follow-up, 22% of children in group 1 had impaired growth, 33% bone age delay, 45% reduced IGF I levels but none had thyroid dysfunction. In group 2, 53% had growth failure, 53% bone age delay, 86% reduced IGF I levels and 40% thyroid dysfunction. Among seroreverters, none showed growth impairment; statistically significant differences were found for height, weight and height velocity between perinatally infected children and seroreverters. Since auxological and hormonal evaluations run parallel to the clinical course of infection, these indices may be useful in monitoring disease progression.

Variability of clinical and immunological phenotype in immunodeficiency-centromeric instability-facial anomalies syndrome. Report of two new patients and review of the literature.

Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a condition characterized by variable combined immunodeficiency, developmental delay, facial anomalies and a variety of structural chromosomal rearrangements. Recently, aberrations at the molecular level have been described consisting of alterations in the methylation pattern of classical satellite DNA. To our knowledge 15 subjects have been described so far in the literature showing marked phenotypic variability. We report on two new patients with normal development and some peculiar clinical and immunological manifestations. All patients previously reported in the literature are reviewed. CONCLUSION. The identification of these two cases among our hypogammaglobulinaemic patients suggests that ICF syndrome is not a rare disorder and it should be always taken into account in immunodeficient patients with facial abnormalities.