Bromohydrin pyrophosphate-stimulated Vgamma9delta2 T cells expanded ex vivo from patients with poor-prognosis neuroblastoma lyse autologous primary tumor cells.

Gamma/delta T cells (Vgamma9delta2) contribute to innate immunity and exert natural cytotoxicity against a variety of tumors. Using a synthetic phosphoantigen (Bromohydrin Pyrophosphate, BrHPP), we amplified Vgamma9delta2 T cells in vitro from neuroblastoma patients. In the presence of BrHPP and low doses of IL-2, robust proliferation of Vgamma9delta2 T cells was obtained from peripheral blood mononuclear cells (PBMC) harvested at diagnosis. Moderate proliferation was observed from PBMC harvested after stem cell transplantation, whereas modest levels of Vgamma9delta2 T cells were obtained from PBMC harvested after induction therapy. Proliferation was observed after a single in vitro stimulation with BrHPP. After 21 days in culture, Vgamma9delta2 T cells represented more than 80% of cultured cells (a 50-fold expansion from baseline). Moreover, BrHPP-amplified Vgamma9delta2 T cells from patients-expressed activation markers and were able to lyse allogeneic and autologous neuroblasts. This cytotoxic activity was gammadelta T-cell receptor-dependent. Clinical trials using BrHPP are warranted in patients with poor-prognosis neuroblastoma, either to expand patient-derived Vgamma9delta2 T cells ex vivo or by direct administration to in vivo to boost the pool of resident Vgamma9delta2 T cells in vivo.

A predictor of unfavourable outcome in neutropenic paediatric patients presenting with fever of unknown origin.

BACKGROUND: No sensitive, specific marker able to discriminate favourable or unfavourable outcome of fever of unknown origin (FUO) at diagnosis has been identified. Procalcitonin, a recently assessed infection marker, may be useful in predicting the outcome of FUO. METHODS: We conducted a prospective study examining the following variables: age 0.5-22 years; solid tumour diagnosis; chemotherapy-related grade-4 febrile neutropenia (FN). A complete clinical, bacteriological and biological evaluation was performed at hospital admission (H0). Other investigations depended on clinical status. FUO was considered to be of unfavourable outcome if the fever was persistent or re-appeared at day 3 (or later), or if secondary clinical or microbiological infection occurred. To validate the results of the analysis the data set was randomly split into a training set and a validation set. RESULTS: Out of 172 episodes of FN, 136 episodes were classified as FUO (80%). Seventy-two (53%) were included in this study. PCT values were significantly higher in episodes of unfavourable outcome (P < 0.001). None of the other prediction candidates appeared to be significantly linked to the risk of unfavourable outcome. In the validation set, the best PCT cut-off was 0.12 micro/L, which was associated with a sensitivity of 80% and specificity of 64%. CONCLUSIONS: PCT-H0 level can predict FUO outcome. A protocol based on PCT-H0 measurement, integrating clinical and bacteriological evaluation, facilitates shorter hospital stays and less antibiotic treatment. Patients with a PCT-H0 value <0.12 micro/L could benefit from an outpatient treatment starting at H48 thus reducing hospitalisation costs and improving quality of life.

Management and successful desensitization in methotrexate-induced anaphylaxis.

Anaphylactic/anaphylactoid reactions to methotrexate are rare. In patients with methotrexate-induced anaphylaxis, discontinuation of treatment may increase the risk of death due to cancer progression. In such patients, desensitization may enable the patient to continue treatment with methotrexate. We report the case of a child with metastatic osteosarcoma, who experienced an anaphylactic/anaphylactoid reaction to methotrexate. Skin tests with methotrexate were not performed because their diagnostic value is controversial. Desensitization with methotrexate was successful and allowed the patient to complete 12 additional courses of chemotherapy. Thus, we confirm that desensitization may be a safe procedure in patients with cancer who experience methotrexate-induced anaphylaxis.

High serological response to pneumococcal vaccine in nephrotic children at disease onset on high-dose prednisone.

Our objective was to demonstrate that nephrotic children at disease onset and under high-dose prednisone respond to vaccination with 23-valent pneumococcal vaccine (PV). We compared the serological response after PV in 30 children with nephrotic syndrome, directly after initiation of prednisone therapy (60 mg/m2 body surface area) at disease onset (group 1), with the response in 13 patients who received the vaccine while in remission (group 2). Safety was studied, comparing disease course in group 1 with those in patients who did not receive any PV (group 3). In group 1, 23-valent PV antibody (Ab) levels increased tenfold after 1 month and remained increased after 1 year (P < 0.01). Ab response in the short term and in the long term was not different from that of patients in group 2. Serum albumin, age, or immunosuppressive drugs did not influence Ab response. Disease courses in groups 1 and 3 were not different. In conclusion, nephrotic children on high-dose glucocorticoid therapy respond to a 23-valent anti-PV. Children with steroid dependent/resistant forms acquire high Ab levels, even if early relapses delay the tapering of steroids or if immunosuppressive agents are introduced. Patients who relapse during the tapering of steroids already have increased anti-pneumococcal Ab at the time of relapse.

Successful treatment for advanced small cell carcinoma of the ovary.

Small cell carcinoma of the ovary is a rare and aggressive malignant tumour with a poor prognosis. The authors describe two females, 12 and 13 years old, who presented with advanced stage disease. They were treated with surgical resection, multiagent chemotherapy and high-dose chemotherapy followed by autologous bone marrow transplantation. They remain free of disease more than 9.5 and 14 years since the diagnosis.