¿Tiene un lugar la radioterapia intraoperatoria en el tratamiento del neuroblastoma? / Is intraoperative radiotherapy of valur in the treatment of neuroblastoma?

Objetivo: Demostrar la utilidad de la radioterapia intraoperatoria (RIO) en el tratamiento de los niños con neuroblastoma en estadios avanzados. Casos clínicos: Presentamos 7 casos de pacientes con neuroblastoma en estadios III (n=1) y (n=6), con amplificación N-myc en 6 de ellos, tratados desde 1997 hata 2004. Dos de los pacientes presentaron tumores irresecables, con restos tumorales macroscópicos tras la intervención. Resultados: La supervivencia en nuestra serie de pacientes ha sido del 71,4%. No hemos registrado ninguna complicación asociada a la RIO. El tiempo medio de seguimiento es de 44 meses (margen: 7 meses-7 años). En el tratamiento del neuroblastoma de grados III-IV se ha observado una mejora de la supervivencia cuando se controla la enfermedad local primaria. Conclusión: La RIO facilita este control, con la concentración de la radioterapia directamente sobre el lecho tumoral y respetando los campos de irradación colaterales

Objective: To report our experience with intraoperative radiotherapy (IORT) in the treatment of advanced-stage neuroblastoma in children. Cases report: Seven pediatric patients with a diagnosis of advanced-stage neuroblastoma (stage III and IV) treated with IORT between 1997 and 2004 were reviewed retrospectively. All of them received chemotherapy after biopsy of the tumour mass (HR-NBL ESIOP protocol), with good response. All seven underwent surgical resection of the tumour, with a single IORT dose of 5 to 15 grays. Results: The initial biopsy showed N-mycamplification in all the patients. Chemotherapy was delivered prior to surgical resection. Gross total resection was performed in five patients. In the other two patients, surgery involved only a debulking procedure. Five patients (71,4%) were alive and continued to be disease-free after 44 months of follow-up, with no IORT associated complications. The two patients with unresectable disease had a fatal outcome. Coclucion: total surgical excision is one of the best prognostic factors in advanced-stage neuroblastoma disease. Intraoperative radiotherapy is a safe procedure that appears to enhance local control with improved survival

B cell function after haploidentical in utero bone marrow transplantation in a patient with severe combined immunodeficiency.

An in utero paternal CD34(+) cell transplant was performed in a T-B+NK+ SCID fetus. We report here the results of the 3-year humoral immune reconstitution study. The methods used were ApoB VNTR typing, flow cytometry, nephelometry, hemagglutination, ELISA, ELISPOT and lymphoproliferative assays. The T cells were of donor origin whereas monocytes, B and NK cells were of host origin. Peripheral B cell counts and IgM levels were normal since birth. IVIG therapy was required at 5 months of age until 2 years old. IgA levels > or =20 mg/dl were detected from month 17 post transplantation. Isohemagglutinins were present since month 8 post transplantation, the highest titers (anti-A:1/128, anti-B:1/32) were obtained at month 33 post-transplantation. After immunization with rHBsAg, circulating anti-HBsAg IgG secreting cells and a 7.8-fold increase in serum anti-HBsAg Ab were detected. We conclude that split chimerism following in utero haploidentical BMT allows complete humoral immune reconstitution in a T-B+NK+ SCID patient.

Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The TEL/AML1 fusion is the most common genetic abnormality found in childhood acute lymphoblastic leukemias (ALL). Although it is very difficult to identify by conventional cytogenetic techniques it can be readily detected using fluorescence in situ hybridization (FISH). We carried out cytogenetic and FISH studies on 42 children with ALL in order to know the frequency of this translocation in our population, the incidence of TEL and/or AML1 gene alterations, and their correlation with clinical evolution and prognosis. In addition, we performed reverse transcription polymerase chain reaction (RT-PCR) in some cases, confirming the feasibility of FISH techniques in the detection of this translocation. DESIGN AND METHODS: Bone marrow samples were obtained from 42 childhood ALL patients. The copy number of AML1 and TEL genes were studied using fluorescent in situ hybridization with a dual color DNA probe specific for the AML1 and TEL genes. RESULTS: We found a frequency of TEL/AML1 fusion of 17% in our sample. Double TEL/AML1 fusion, lack of TEL signal and extra AML1 signals were frequent additional FISH abnormalities. Duplication of a chromosomal complement, deletion of chromosome 12p arm, and polysomies of chromosome 21 are plausible explanations for these additional FISH findings. However, a relatively high proportion of our cases (9.5%) presented specific amplification of AML1. A statistically significant difference in prognosis was found between patients with and without these additional AML1 or TEL FISH alterations (p<0.02), which could be related to the presence of specific karyotypes. INTERPRETATIONS AND CONCLUSIONS: The frequency of TEL/AML1 fusion is similar to that found in other populations (17%). We found that FISH analysis of AML and TEL is related to the evolution of the disease. The absence of alterations in these genes revealed by FISH could be indicative of bad prognosis, while the presence of alterations is related to a good evolution. Our results suggest that interphase FISH analysis to search for alterations in AML and TEL genes could be extremely useful for complementing cytogenetic studies and for providing additional information about the possible outcome of the disease in patients with ALL.

[The role of intraoperative radiotherapy in oncological pediatric surgery]. / Papel de la radioterapia intraoperatoria en la cirugía pediátrica oncológica.

Conventional external beam radiation has proved its profit in pediatric tumors; but its complications have limited it in therapeutical approach. Intraoperative radiotherapy delivers a high single dose in residual tumor or high risk areas during surgery. In our center, during last two years, 7 patients have been candidates to surgery with intraoperative radiotherapy (the age range was between 5 months-17 years; mean 8.5 years). Two patients were excluded of our protocol because of their intraoperative stage. Patients tumors types were: neuroblastoma (n = 3; stage III and IV), soft tissue sarcomas (n = 1) and Ewing's sarcoma (n = 1). The radiation doses ranged from 500 cGyto-1200 cGy. Local control tumor was achieved in 4 patients and no-complications were present secondary to surgery or intraoperative radiotherapy. Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors with protection of normal tissues and could be an excellent complement in special cases.

Fanconi's anaemia: case history of six Spanish families.

We report on the results obtained in 6 Fanconi's anaemia families (FA) (parents, brothers and sisters) affected by at least one of the symptoms usually observed in FA. The 6 FA families were studied from 1974 to 1990, all having located in Madrid (Spain) but with different ethnic origin: 3 families are of Spanish descent and the other 3 are gipsy families. All showed characteristics of the disease, including malformations, stunted growth, microcephaly, skin hyperpigmentation, high incidence of chromosomal breaks in lymphocyte cultures, and hematological and biochemical abnormalities: pancytopeny, increased fetal hemoglobin levels and significantly decreased superoxide dismutase (SOD) activity. (Ref. 17.)

Superoxide dismutase and other biochemical disorders in a family with Fanconi's anemia.

Activities of superoxide dismutase, glutathione reductase, pyruvate kinase and glucose-6-phosphate dehydrogenase and level of fetal hemoglobin were determined in a family with Fanconi's anemia. Superoxide dismutase activity was significantly decreased, but glutathione reductase, pyruvate kinase and glucose-6-phosphate dehydrogenase activities were normal. The fetal hemoglobin levels observed were increased when compared with standard levels.

Hepatosplenic gamma-delta T-cell malignant lymphoma: report of the first case in childhood, including molecular minimal residual disease follow-up.

We report the first case of T-cell gamma delta+ hepatosplenic malignant lymphoma in childhood. Tumour-specific oligoprobes were developed against the single V1-J1 rearrangement of the delta T-cell receptor (TCR) gene in order to perform minimal residual disease (MRD) studies. Molecular analysis in serial bone marrow samples proved to be of predictive value concerning the clinical outcome. Clonotypic DNA was not detected in peripheral blood during the course of the disease until a refractory terminal leukaemic phase took place 18 months after the diagnosis. This case demonstrates the usefulness of MRD studies to monitor the course of disease in at least some subsets of peripheral T-cell lymphomas.

[Second tumors in childhood]. / Segundos tumores en la infancia.

More aggressiveness in treatment of childhood malignancies has had an evident impact on survival and rate of cure but, it has also allowed us to discover long-term effects of these treatments, and second malignant tumors of them. Between 1970 and 1993, 472 cases of malignant tumors in childhood were diagnosed in our department. Six of them (1.27%) developed a second tumor (five malignant and one benign). Relationship between first and second tumors are: seven years old boy, cervical lymphosarcoma-thyroid carcinoma; eleven years old boy, osteogenic sarcoma-vesical carcinoma: two years and six months old boy, cerebellar astrocytoma-soft tissue osteogenic sarcoma; five years old girl. Wilm's tumor-scapular osteogenic chondroma; one year and a half old girl, abdominal neuroblastoma-granulocytic sarcoma (chloroma); twelve years old boy. Hodgkin's disease-acute myeloblastic leukemia. All of them were clearly related to concogenic effect of radiation or chemotherapy.