Infliximab for GVHD therapy in children.

GVHD remains a significant complication of allogeneic hematopoietic stem cell transplantation. Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of GVHD pathogenesis. Infliximab inhibits the binding of TNF-alpha with its cellular receptors and has been associated with encouraging responses in adults with severe GVHD. We retrospectively evaluated the efficacy and safety of infliximab 10 mg/kg i.v. once a week for a median of eight doses (range 1-162) in 24 children with steroid-resistant GVHD. The overall response rate in 22 evaluable children was 82% (12 CR+6 PR). Among those patients with acute GVHD, both skin and gastrointestinal involvement responded well to infliximab; however long-term outcome was poor. While infliximab may be useful to acutely control GVHD manifestations, GVHD recurs commonly upon discontinuation of infliximab. Within 100 days of the final infliximab dose, 77% of patients had bacterial infections, 32% had viral infections and 13.6% had probable or proven non-candidal invasive fungal infections. Infliximab appears to be well-tolerated and to have activity in steroid-resistant GVHD. Controlled studies to assess the pharmacokinetics and most effective dosing regimen of infliximab for the treatment of GVHD are warranted.

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Correction of autoimmune lymphoproliferative syndrome by bone marrow transplantation.

This report describes a child with a severe phenotype of autoimmune lymphoproliferative syndrome (ALPS) who developed progressive disease requiring stem cell transplantation. This severe form of ALPS was associated with a novel Fas gene splice site mutation that resulted in functional deletion of exons 8 and 9. While this child shared many clinical features with previously described ALPS cases, including massive lymphadenopathy and circulating alphabeta+ CD3+CD4-CD8-T cells, his disease progressed despite immunosuppressive therapy to a clinically aggressive oligoclonal lymphoproliferation which resembled a diffuse large cell non-Hodgkin's lymphoma. After partial remission was achieved with cytotoxic therapy the patient underwent BMT from an unrelated donor. This is the first reported case of ALPS in which BMT was successfully attempted for correction of a Fas deficiency.

Stroke in a neonate heterozygous for factor V Leiden.

Activated protein C resistance is the most common hereditary coagulation abnormality and is caused by the factor V Leiden mutation. A newborn who developed seizures within hours after delivery and was found to have a bihemispheric stroke is described. This patient, determined to be heterozygous for factor V Leiden, is the first reported case of neonatal stroke associated with this common mutation.

S-cells from a highly N-myc-amplified neuroblastoma are tumorigenic in nude mice.

Some neuroblastoma tumors when cultured in vitro give rise to N (neuronal) and S (non-neuronal) cells, which differ in morphology, state of differentiation, and tumorigenicity. Previously, tumor-forming potential was shown to be characteristic of N cells but not S cells. We examined cultures of N and S cells derived from a well-characterized, N-myc-amplified human neuroblastoma cell line, NBL-W, to determine whether these N and S cells also show differential tumorigenicity in nude mice. N cells formed tumors in 94% of trials and S cells formed tumors in 56% of trials. Although S cell tumors had a longer lag phase prior to tumor development, when tumors developed, both N and S cell-derived tumors grew rapidly. These results suggest that S cells do not always represent a benign component of neuroblastomas.

Henneguya episclera sp. n. (Protozoa: Myxosporida), a new myxosporidan from the eye of the pumpkinseed sunfish.

Henneguya episclera sp. n. is described from the episclera of the eye of the pumpkinseed sunfish (Lepomis gibbosus). Mean spore dimensions (in micrometers) are: total length 62.6; spore length 21.7; spore thickness 8.0; spore breadth 8.7; tail lengths 37.1 and 40.9; polar capsule lengths 6.0 and 6.5; polar capsule breadths 2.7 and 3.0; polar capsule thickness 3.5; and vacuole 5 by 5.