Mutational analysis of N-RAS and GAP-related domain of the neurofibromatosis type 1 gene in chronic myelogenous leukemia.

RAS mutations can be detected in a variable number of patients with myeloproliferative disorders such as myelodysplastic syndromes and acute myeloid leukemia, but are rare events in chronic myelogenous leukemia in chronic phase. However, there is good evidence supporting the involvement of RAS signalling pathway in CML and this could be due to alterations in RAS activity regulatory proteins. The neurofibromatosis (NF1) gene down-regulates the RAS signal transduction pathway through the inhibitory function of its GAP-related domain (GRD) on RAS protein. The loss or alteration of neurofibromin (the NF1 protein) may produce a disfunction similar to point mutations in the RAS gene resulting in the permanent stimulation of the RAS signal transduction pathway. Mutations involving the GRD region of the NF1 gene (GRD-NF1) have been described in a variety of tumors such as colon carcinoma and astrocytoma. Germline mutations and deletions in the NF1 gene, as seen in neurofibromatosis type 1, are also associated with certain myeloid disorders. In the present work, we sought to identify mutations in the codons 12/13 and 61 of RAS gene and in the Lys-1423 codon of GRD-NF1, which are well known hot spots in these genes, in a group of 36 adults and ten children with chronic myelogenous leukemia in chronic phase and blast crisis. Using the PCR-SSCP and the allele-specific restriction assay (ASRA) techniques, we were not able to observe any RAS or NF1 detectable mutation. These findings suggest that RAS and GRD-NF1 mutations are not involved either in chronic phase or in the progression to blast crisis in chronic myelogenous leukemia in adults and children.

Treatment results of three consecutive Brazilian cooperative childhood ALL protocols: GBTLI-80, GBTLI-82 and -85. ALL Brazilian Group.

The Brazilian Cooperative Group for Treatment of Childhood Acute Lymphocytic Leukemia (GBTLI) has started clinical activities trials in 1980. Three consecutive multicenter studies in children with unprevious treated ALL have been completed including 994 patients. The first GBTLI-80 accrued 203 children from 1980 to 1982. It was delineated with the standard three drugs induction therapy, CNS protection for all pts comprised cranial irradiation and intrathecal Methotrexate. For low risk pts cranial irradiation with 18Gy was compared in a randomized trial with 24Gy. Maintenance therapy continued for 120 weeks. The 12 years of the event free survival rates for all risk groups is 50% (SD 5%). Regarding CNS relapses there was no significant statistical difference between pts that received 18 or 24Gy. The treatment strategy of GBTLI-82 (n = 360) from 1982 to 1985, consisted of the same previous induction, consolidation, CNS therapy with cranial irradiation 18 Gy (low risk) or 24Gy (high risk), followed by continuous maintenance for 2 years. The main question in this study was the comparison between sequential rotation or pulses of 3 pairs of drugs during maintenance. At a median follow-up of 10 years, the overall event free survival rates for all children is 58% (SD 4%). There was no significant difference between the two maintenance regimens. The successor GBTLI-85 ran from 1985 to 1988 and registered 431 pts. For the first time no cranial radiation was given to children with very good prognosis. For them, CNS protection was done with triple intrathecal therapy during all treatment. A consolidation therapy with high dose ARA-C was introduced for high risk pts and infants The 6.5 years event free survival for all children is 70% (SD 4%). Significant better results were achieved for high risk and infants pts (EFS 50%). Early intensification therapy and rotational combination chemotherapy improved the outcome in childhood ALL in Brazil.

Doença de Chagas aguda: vias de transmissäo aspectos clínicos e resposta a terapêutica específica em casos diagnosticados em um centro urbano / Acute Chagas' disease: transmission routes, clinical aspects and response to specific therapy in diagnosed cases in an urban center

Relata-se o quadro clínico de 27 pacientes com doença de Chagas aguda, acompanhados no ambulatório da Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da FM-USP no período de 1974 a 1987. As vias de transmissäo envolvidas foram: vetorial em 7 casos, transfusional em 9, transplante de rim e/ou transfusional em 4, acidental em 1, via oral em 3, provável alcitamento materno em 1, congênita ou aleitamento materno em 1, congênita ou transfusional em 1. Pacientes com infecçäo por via vetorial eram procedentes da Bahia e Minas Gerais, infectados por via transfusional adquiriram a doença na Grande Säo Paulo, 7 deles após 1983. O quadro clínico foi oligossintomático ou assintomático em 4 pacientes, sendo 3 deles imunodeprimidos por doença de base ou por medicamentos. Em outros 2 pacientes imunodeprimidos ocorreu miocardite grave com insuficiência cardíaca congetiva. O quadro clínico foi também mais grave em 5 de 6 crianças menores de dois anos de idade, qualquer dque fosse a via de transmissäo

Poland's syndrome associated with childhood non-Hodgkin's lymphoma.

Poland's syndrome is a congenital absence of the sternal portion of the pectoralis major muscle, often associated with ipsilateral upper-limb anomalies. We describe two children with non-Hodgkin's lymphoma associated with Poland's syndrome, ie, an association between childhood cancer and congenital anomalies previously unreported and unlikely to be due to chance. In addition, we report another case of acute leukemia in a child with Poland's syndrome. In view of the rarity of Poland's syndrome in the general pediatric population, we conclude that there is an increased association of the syndrome with both leukemia and non-Hodgkin's lymphoma, the biologic basis of which is unclear.

The natural history of colorectal carcinoma in adolescents.

The symptoms, histology, extent, and course of disease of 24 adolescents with colorectal carcinoma who were admitted to St. Jude Children's Hospital between 1964 and 1980 are presented. Twenty of the patients were referred between October 1974 and June 1980. Most patients presented with vague abdominal complaints. Twenty-one of the 24 patients had poorly differentiated mucin-producing adenocarcinoma. Extensive disease at diagnosis and unresponsiveness to medical management was reflected in the eight-month median survival from diagnosis. Only two of the 24 patients survive free of disease 15 and 130 months from diagnosis. Two other patients survive with disease at four and 24 months.