Are basic fibroblast growth factor and vascular endothelial growth factor prognostic indicators in pediatric patients with malignant solid tumors?

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Among angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) appear to be useful markers in adults with cancer. The aim of this pilot study was to determine the levels of VEGF in serum and bFGF in serum and urine of children with solid tumor at diagnosis (as measured by ELISA), and to investigate whether these parameters provide prognostic information. Forty consecutive patients with different types of cancer were prospectively included in this study. Median values of all studied angiogenic factors were higher in patients than in controls (n = 40), and the differences were statistically significant for bFGF in serum and urine: 10 versus 3 pg/ml (P = 0.0004) and 6406 versus 0 pg/g of creatinine (P < 0.0001), respectively. Among patients, median serum values of bFGF and VEGF were higher in children with metastatic disease (n = 14) than in those with localized disease (n = 26). The difference was statistically significant for serum bFGF: 17.5 versus 6 pg/ml (P = 0.02). Serum angiogenic factor levels correlated with outcome. The estimated event-free survival at 3 years was 79% for patients with normal bFGF values (n = 13) versus 42% (n = 26; P = 0.02) for those with high levels, and 71% in case of normal VEGF values (n = 20) versus 38% (n = 19; P = 0.04) for those with high levels. No benefit of normal urinary bFGF values was observed. Our results provide a rationale for exploring the clinical interest of bFGF and VEGF measurements in body fluids of a larger group of children with cancer.

[Klebsiella oxytoca septicemia following platelet transfusion]. / Septicémies a Klebsiella oxytoca après transfusions de plaquettes.

Two fractions of a three-day-old apheresis platelet collection from a known habitual donor were transfused to two children with thrombocytopenia and bleeding. Both patients developed evidence of severe infection during the transfusion. One died despite intensive care and antimicrobial therapy. The other, whose transfusion was cut short, recovered. A Klebsiella oxytoca strain was recovered from the two transfusion bags, from a third unused bag, and from blood samples from the patient who died. Genotyping results established that all these isolates were identical. Tests for K. oxytoca were negative on the batches of blood donation material, the bottle of antiseptic used, and throat and stool specimens from the donor and phlebotomists. The most likely hypothesis is that the donor developed transient asymptomatic bacteremia during the 136-minute-long collection procedure and that the organism subsequently grew in the platelet collections, which were kept at 20-24 degrees C with agitation for three days before being used.

[Transfusion in sickle cell anemia]. / La transfusion dans la drépanocytose.

Although blood transfusion (BT) therapy remains a key component of the weaponry used to treat acute and chronic sickle cell disease complications, its indications and modalities are currently the focus of a critical reappraisal prompted by the introduction of hydroxyurea, recent improvements in allogeneic bone marrow transplantation, and increasing attention to safety concerns. Expected benefits of each BT should be carefully weighed against the risks of infections, immunologic complications, and iron overload. Simple or exchange BT can be used. In emergency situations, the only effective means of improving tissue oxygenation and limiting blood vessel occlusion is dilution or removal of HbS by simple or exchange BT, respectively; simple BT is indicated in severe anemia or acute hypovolemia and exchange BT in acute vasoocclusive crisis or acute infection. In nonemergency situations, long-term exchange BT programs geared to maintain the HbS level around 30% are used to stabilize existing lesions and to prevent recurrences; they have been proved effective in preventing recurrent stroke in patients who are not candidates for allogeneic bone marrow transplantation. Situations in which BT therapy is widely used despite controversy regarding its value and modalities include the prevention of complications of pregnancy, the prevention of perioperative complications, and the prevention of recurrences of severe vaso occlusive crisis in patients eligible for hydroxyurea therapy. Advances have been made in the minimization of BT-related complications (alloimmunization, viral infections, iron overload) through critical appraisal of the need for each BT, careful selection of the most appropriate blood product, and a change in BT technique resulting in a reduction in the number of blood donors.

[Erythrocytapheresis a few weeks before surgery: an alternative to erythropoietin treatment in programmed autologous transfusion]. / L'érythrocytaphérèse quelques semaines avant l'intervention: une alternative au traitement par érythropoïétine en transfusion autologue programmée.

The usual methods like hypotension, isovolaemic haemodilution, autologous transfusion and peri-operative blood salvage may significantly reduce the need for homologous blood transfusion in haemorrhagic surgery and also the risk of transmitting infectious agents. Erythropoietin (EPO) is now available and is used to stimulate red cell regeneration in pre-operative autologous blood donation. In acute anaemia, many studies have shown that the stimulation of endogenous erythropoietin production could be very high and accelerate red blood cell production. Taking higher quantities of blood than usual induces a secretion of endogenous erythropoietin, and could be an alternative for the utilization of exogenous EPO in autologous blood donation.

Specific elimination of alloreactive T cells by an anti-interleukin-2 receptor B chain-specific immunotoxin.

Graft-versus-host disease and graft rejection remain the two principal causes of morbidity and mortality after major-histocompatibility-complex-mismatched bone marrow transplantation. Human and animal models suggest that both CD4+ and CD8+ T cell subsets present in the donor inoculum are responsible for their initiation. Since the human mixed lymphocyte culture (MLC) and the HLA-restricted cytotoxicity may reflect cellular interactions occurring during GVHD and graft rejection, inhibitions of these responses may represent useful approaches for screening functional T cell depletion in experimental bone marrow transplantation studies. For this purpose, we have tested the possibility of removing the host-specific allogeneic T cells present in the marrow. After a two-day MLC, the specifically activated host alloreactive blood or bone marrow T cells were incubated with the ricin A-chain toxin conjugated with the antibody 33B3.1 directed against the human receptor of interleukin 2 (33B3.1-IT). A complete inhibition of a primary MLC and of cytotoxic activities was observed as well as a disappearance of IL-2R(+) (p55) T cells. This method had limited consequence upon the alloreactivity of blood or marrow T cells toward a third unrelated party. The limiting-dilution analysis of residual alloantigen-reactive T lymphocytes has shown that this depletion results in a twentyfold to fiftyfold reduction of antihost reactivity. The procedure was also shown not to inhibit the growth of marrow precursors for granulocytes and macrophages.

Collection of placental blood with a view to hemopoietic reconstitution.

Collection of placental blood in a sterile and closed system is a simple, safe and efficient procedure. One hundred and fifty eight units of fetal blood were collected by applying the same requirements of quality and safety as those defined for blood products in blood banks. No adverse effects were seen in mothers or their newborns.

[The place of bone marrow autografts in the treatment of Hodgkin's and non-Hodgkin's lymphoma]. / Place des autogreffes médullaires dans le traitement des lymphomes hodgkiniens et non hodgkiniens.

The therapeutic approach to relapses in aggressive non-Hodgkin's lymphoma has been changed by high dose chemotherapy and autologous bone marrow graft. In the absence of dramatic improvement following the conditioning regimen, such a procedure should be reserved for patients still sensitive to salvage therapy. Up to 40%-50% of these selected cases can expect prolonged disease-free survival. Autologous bone marrow graft in first remission should only be considered in poor prognosis patients in a carefully randomized study. In Hodgkin's disease, relapses and patients in partial remission after MOPP and ABVD treatment are potential candidates for autologous bone marrow graft. Preliminary results indicate a disease-free survival up to 50%.

HLA-haploidentical bone marrow transplantation for severe combined immunodeficiency using E rosette fractionation and cyclosporine.

Eight patients with severe combined immunodeficiency received bone marrow cells from their HLA haplotype-identical fathers after bone marrow T cell depletion by rosetting with neuraminidase-treated sheep red cells. Because the method led to the infusion of a small percentage of T lymphocytes (0.1% to 0.3%), cyclosporin was given by continuous intravenous infusion for two months in order to prevent the occurrence of graft-v-host disease (GVHD). Three patients who did have residual nonfunctional T lymphocytes received busulfan and cyclophosphamide before transplantation. Engraftment was observed in seven patients, and severe GVHD was not seen. Two patients died early after the bone marrow transplantation because of prior infections, and a third died at day 90 from a B cell lymphoproliferative syndrome. The five other patients are doing well. Stable engraftment has been achieved with reconstitution of cell-mediated immunity in 5/5 and humoral immunity in 4/5 patients.

Bone-marrow transplantation for inborn error of phagocytic cells associated with defective adherence, chemotaxis, and oxidative response during opsonised particle phagocytosis.

Two girls had delayed umbilical cord detachment, recurrent bacterial infection, inability to form pus, and marked leucocytosis. Their phagocytes were defective in tests of adherence, random migration, chemotaxis, and oxidative burst. NK activity was virtually absent. This rare disorder, due to an inherited absence of a 180 kilodalton membrane glycoprotein on polymorphonuclear cells, is usually lethal within 2 years. Allogeneic HLA-matched bone-marrow transplantation done at ages 4 months in one patient and 2 years in the other after intensive conditioning was successful and resulted in nearly complete correction of phagocytic cell function and NK activity within two months. One patient died 9 months after transplantation from severe chronic graft-versus-host disease with obstructive bronchopneumopathy. The other is doing well 1 year after transplantation and showing stable chimerism and normal phagocytic function.

[Asplenia: a study of 21 subjects splenectomized during childhood for spleen injury (author's transl)]. / L'asplénie. Etude de 21 sujets splénectomisés dans l'enfance pour traumatisme.

Clinical and biological studies were carried out in 21 subjects one to twenty-three years after the injured spleen had been removed. Asplenia did not give rise to clinical symptoms, did not facilitate infections and had no effect on growth. Laboratory investigations revealed a decrease in IgM in 6 subjects and minor quantitative and qualitative platelet abnormalities. The absence of Jolly's bodies in 7 subjects was suggestive of spleen regeneration, which was confirmed by scintigraphy in 2 cases. The significance of these findings in discussed.

Functional abnormalities of neutrophils in cancer patients : inefficient phagocytosis and reverse endocytosis.

A study of neutrophil functions has been performed in 17 patients with advanced cancer and in 21 controls. Their phagocytic activity, their index of reduction of NBT and their myeloperoxidase activity were examined. The reslts suggest that cancer patients might have a "factor" or "factors" in their plasma which interfereu (s) with phagocytosis and which promote (s) exocytosis of lysosomal enzymes ("reverse endocytosis") from from autologous polymorphonuclear leucocytes as well as from cells obtained from normal healthy donors.

[Changes in bone marrow cellularity close to cancer metastases. Cyto-histologic study]. / Modifications de l'environnement médullaire au contact des métastases de cancers. Etude cyto-histologique

Before starting any therapy, we systematically studied by biopsy the bone marrow of 66 patients suffering from various cancers and suspect of marrow metastasis. Metastatic cells were thus found in 45 patients. Bone marrow composition was examined on histologic sections by granulometric method, while relative proportions and morphology of the various hematopoietic series were examined on cytologic prints. It then appeared that any important metastatic invasion goes together with deep alterations of the surrounding hematopoietic tissue, with frequent peri-metastatic collagenic fibrosis and hypoplasia of the various cell-lines; when metastatic growth is still moderate, hematopoietic tissue is, on the contrary, often hyperplastic, "irritative". These marrow alterations are not to be found far from the metastasis, and thus seem to be directly linked to the actual presence of cancerous cells.