X-linked adrenoleukodystrophy: clinical course and minimal incidence in South Brazil.

UNLABELLED: X-linked adenoleukodystrophy is a genetic disease that affects the degradation of very long-chain fatty acids. In male patients, common pictures are the cerebral form (CALD), myeloneuropathy (AMN), and Addison-only. OBJECTIVE: To describe the clinical course of affected male patients from South Brazil between 1993 and 2007. METHODS: Affected male patients and their maternal lineages were studied from a clinical, neurological and biochemical standpoint. RESULTS: Eighty-three male patients from 30 families were biochemically evaluated: 51 were affected. 27/51 (54%) presented the cerebral form; 11/51 had AMN (22%); 5 had Addison-only (10%), and 8 (16%) were asymptomatic. Between 2002 and 2006, the minimal incidence was 1:35,000 males in our State (South Brazil). Forty-three affected individuals were followed for 5.4+/-3.7 years. Of 10 boys detected at early stages, three developed CALD. These three boys and another five CALD at baseline were referred to hematopoietic stem cell transplantation. Seven transplants were carried out, 5 with good clinical evolution after 2.2 years post-transplant. The non-transplanted case was later defined as a stable cerebral form. DISCUSSION: Among the present families, the observed cases were comparable to the 50% expected by Mendelian segregation. Based on the natural history, the number of cases that developed CALD was similar to the expected. Transplants were successful in 70% of cases. The occurrence of a stable cerebral form pointed to an urgent need for better markers of active cerebral disease.

Oral health and dental anomalies in patients treated for leukemia in childhood and adolescence.

BACKGROUND: This study was conducted to evaluate oral health and dental anomalies in children treated for acute lymphoblastic leukemia (ALL) and to compare results with those of a group of healthy children matched for sex and age. PROCEDURE: Fifty-six children treated for ALL and 56 healthy controls were examined for dental anomalies, and data on decayed, missing, and filled teeth (DMFT) score, visible plaque (VPI), and gingival bleeding (GBI) indices, and saliva flow were collected. Mean age of all children treated for ALL was 5.3 +/- 2.6 years at diagnosis and 11.8 +/- 4.2 at evaluation. Thirty-two were males. RESULTS: Forty-five treated children (80.4%) had at least one dental anomaly, and patients treated with chemotherapy, radiotherapy, and bone marrow transplantation had the greatest mean number of dental anomalies (15.37 +/- 15.03). Patients younger than 5 years at beginning of treatment were also more affected (P = 0.031). Children treated for ALL had a DMFT score of 1.9 +/- 4.0, GBI of 26.5%, VPI of 72.0%, and mean saliva flow of 0.19 ml/min; healthy children had a DMFT score of 1.52 +/- 3.5, GBI of 11.1%, VPI of 53.8%, and mean saliva flow of 0.27 ml/min. CONCLUSION: The treatment of ALL causes a significant increase in the number of dental anomalies. Their GBI and VPI were also elevated. Changes in salivary glands during treatment did not affect saliva flow permanently. Follow-up of these patients by an oral health team is recommended.

Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models.

Malignant gliomas have a dismal prognosis despite multi-modality treatments like neurosurgical resection, radiation therapy and chemotherapy. Evidence has indicated that gastrin-releasing peptide (GRP) and its receptor (GRPR) play a role in the development of a variety of cancers including gliomas. In the present study, we investigated the effects of RC-3095, a selective GRPR antagonist, alone or in combination with temozolomide (TMZ), a DNA alkylating agent, in in vitro and in vivo experimental rat C6 glioma models. Cellular proliferation was significantly reduced by all treatments with the combined administration of TMZ and RC-3095 being the most effective treatment. In in vivo experiments, the control group displayed the largest tumors (52 +/- 15.5 mm(3)), whereas RC-3095 reduced the tumor size, with the most significant effect at the dose of 0.3 mg/kg (21 +/- 9.7 mm(3)). The combined therapy produced further reduction in tumor size (10 +/- 7.5 mm(3)). Our results show that the combination of RC-3095 with TMZ produced an important reduction in in vitro and in vivo glioma growth therefore making RC-3095 a candidate drug to potentiate the effects of the DNA alkylating agent TMZ in the treatment of glioma.

[Clinical and epidemiological analysis of bone marrow transplantation in a pediatric oncology unit]. / Análise clínica e epidemiológica do transplante de medula óssea em um serviço de oncologia pediátrica.

OBJECTIVE: To describe the demographics and the most important acute clinical complications in patients undergoing bone marrow transplantation in the Pediatric Oncology Unit at Hospital de Clínicas de Porto Alegre, Brazil. MATERIAL AND METHODS: A retrospective analysis was performed including 41 patients treated between August 1997 and June 2002. Twenty patients received allogeneic transplants (AG) and 21 received autologous transplants (AT). RESULTS: The mean age of AG patients was 8.9 +/- 5.4 years. Twelve patients were male. Stem cell sources were: bone marrow in 12 patients; peripheral blood in five; and unrelated cord blood in three. The diseases were acute lymphoid leukemia in seven patients; acute myeloid leukemia in four; chronic myeloid leukemia in two; myelodysplastic syndrome in two; Burkitt's lymphoma in one; severe combined immunodeficiency in one; Chediaki-Higashi syndrome in one; Fanconi anemia in one; and aplastic anemia in one. One patient developed grade II acute graft-versus-host-disease (GVHD), and three patients had grade IV GVHD. Three patients developed chronic GVHD. In all of them, the cell source was peripheral blood. Survival in this group was 70.0 +/- 10.3%. The main cause of death was GVHD in three patients and sepsis in another three. All deaths occurred before day 100. One of the patients who received unrelated cord blood is alive 3.5 years after the transplantation. In AG patients, mean age was 8.7 +/- 4.3 years. Eleven patients were male. The stem cell sources were: peripheral blood in 16; bone marrow in three; and peripheral blood + bone marrow in two. The diseases were: Wilms' tumor in five patients; Ewing's sarcoma family tumors in four; neuroblastoma in three; Hodgkin's disease in three; non-Hodgkin's lymphoma in one; rhabdomyosarcoma in two; neuroectodermic tumor of the central nervous system in two; acute myeloid leukemia in one. Survival in this group was 59.4 +/- 11.7%. Five patients died due to tumor relapse, two patients due to sepsis and one patient died in remission 20 months after bone marrow transplantation due to infection. In the whole group, the most common toxicities were vomiting, mucositis, diarrhea and abdominal pain. Infections were recorded in 58.5% of the patients. In 46.9%, at least one pathogen was isolated in the blood culture. The time required for neutrophil and platelet engraftment was correlated to the number of hematopoietic stem cell infused. CONCLUSION: The overall survival in our patients is similar to that reported in the literature. We did not find differences between AT and AG patients regarding acute toxicities and infections.

High-dose chemotherapy and autologous peripheral blood stem cell rescue in a patient with pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor of the lung. Approximately 80 cases of PPB have been published, and in only three cases high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) was applied. A 5-year-old girl presenting with cough, fever, and shortness of breath was referred to the authors in March 1999. A computed tomography scan of the chest showed a tumor mass in the left hemithorax. The lesion was biopsied and the histopathologic report suggested the diagnosis of PPB. The patient received chemotherapy comprising vincristine, actinomycin D, and cyclophosphamide with only a minor response, and treatment was switched to ifosfamide, carboplatin, and etoposide, which produced a partial response. Tumor resection was performed, but margins were positive for PPB. Due to the high risk of recurrence, the authors elected to administrate high-dose chemotherapy using melphalan, etoposide, and carboplatin, followed by autologous HSCT. The patient achieved complete hematologic recovery, and reimaging after HSCT showed no evidence of disease. She relapsed 4 months later and died about 9 months after the completion of high-dose therapy. The role of high-dose chemotherapy and autologous HSCT is likely to be limited in PPB.

[Bone marrow transplantation and cord blood transplantation in children] / Transplante de medula óssea e transplante de sangue de cordão umbilical em pediatria.

OBJECTIVE: To review the indications, main steps and complications of bone marrow transplantation in children. SOURCES: Medline-based literature review. SUMMARY OF THE FINDINGS: We comment about the indications of autologous, allogeneic and syngeneic bone marrow transplantation, donor selections, harvest and infusion of the hematopoietic progenitor cells that will reconstitute the hematopoietic and immune systems. We describe the different conditioning regimens and the new sources of cells, such as cord blood. We also describe the most common events after the procedure, including infections, graft versus host disease, and cardiovascular, pulmonary, hepatic, genitourinary, and gastrointestinal complications. The late effects and their impact on quality of life are also discussed. CONCLUSIONS: Bone marrow transplantation does not confer an absolutely normal life span to all the patients; however, it represents the only chance of cure for children with certain neoplastic or immunological diseases. By knowing the steps of the procedure, pediatricians can be a source of information on bone marrow transplantation to the patients and their families.