[Severe acquired aplastic anemia: historical outcome of patients treated by allogeneic bone marrow transplantation from matched sibling donors. A study by the Spanish Group for Bone Marrow Transplantation in Children (GETMON)]. / Aplasia medular grave adquirida: evolución histórica de los resultados obtenidos con trasplante de progenitores hematopoyéticos de donante familiar. Estudio del Grupo Español para el Trasplante de Médula Osea en Niños (GETMON).

INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation is the treatment of choice for acquired aplastic anaemia in children. Experience with this approach from Spanish Working Party for Bone Marrow Transplantation in Children in two sequential time periods (1982-1990 and 1991-2004) is reported. PATIENTS AND METHODS: Sixty two consecutive patients with a median age of 10 years were transplanted; 18 in the 1982-1990 period and 44 in the 1991-2004 period. Conditioning regimen consisted mainly of irradiation and cyclophosphamide in the first period (72 % of patients) and cyclophosphamide +/- anti-thymocyte globulin (62 %) in the second. Graft versus host disease prophylaxis consisted of cyclosporine in most patients (57/62). RESULTS: Fifty one patients are alive and disease-free at a median follow-up of 127 months. Five years probability of event-free survival is 82 %. The survival increased from 61 % to 91 % during the two time periods. Eleven patients died from graft failure or rejection (3), acute or chronic graft versus host disease and infection (4) or multi-organ failure (4). Univariate analysis identified two significant prognostic factors: interval diagnostic/transplant and time period of transplant (for both p = 0.03). CONCLUSIONS: This experience corroborates that allogeneic haematopoietic stem-cell transplantation is the best treatment for severe acquired aplastic anaemia, with a current disease-free survival of 90 % of patients.

[Systemic myofibromatosis in an infant]. / Miofibromatosis infantil sistémica en un lactante.

Infantile myofibromatosis is characterized by the presence of solitary or multicentric fibrous nodules in skin, muscle and/or internal organs. Despite being an infrequent entity, and consequently little known by pediatricians, it constitutes the most frequent fibrous tumor in children. Solitary cutaneous lesions have a very good prognosis but in some cases there is systemic involvement. In these cases the disease can produce serious complications and even put the patient's life at risk, especially during the first months of life. These complications are due to the locally invasive nature of the nodules, obstruction of vital organs, growth retardation or infection. We present the case of an infant who at birth presented a skin nodule only. Over time, the infant presented lesions in skin, bone and internal organs. The infant showed respiratory distress requiring mechanical ventilation due to diaphragmatic paralysis. We recommend close follow-up of all patients with infantile myofibromatosis to prevent or make an early diagnosis of these complications

[Evaluation of gonadal function in post-pubertal patients after bone marrow transplantation during childhood objective]. / Evaluación de la función gonadal en pacientes pospuberales sometidos a trasplante de médula ósea durante la infancia.

AIM: To evaluate the effect of bone marrow transplantation during childhood on gonadal function in postpubertal patients. METHODS: We studied 19 post-pubertal patients (13 males, 6 females) aged 13-20 years, 2-9 years after bone marrow transplantation for diverse diseases. Fifteen patients had received multi-agent cytotoxic treatment and 6 had received cranial irradiation prior to transplantation; eleven patients received total body irradiation. Gonadal function was assessed by typifying Tanner's stages of pubertal development and by measuring testicular volume in males (Prader's orchidometer). Serum concentrations of luteinizing hormone, follicle-stimulating hormone, testosterone and 17-beta-estradiol were also measured. RESULTS: Twelve patients were found to have gonadal dysfunction of gonadal origin. Of these, three had not received total body irradiation. CONCLUSIONS: The results obtained show that gonadal dysfunction is frequent in patients treated with bone marrow transplantation. This damage can be attributed to both chemo- and radiotherapy but a synergistic effect between these treatments could not be excluded. The prepubertal status of patients at the moment of transplantation was not a protective factor against chemo- or radiotherapy-induced gonadal damage in our series.

[Transplantation of umbilical cord blood hematopoietic progenitor cells in children]. / Trasplante de progenitores hematopoyéticos de sangre de cordón umbilical en niños.

AIM: Retrospective study of the outcome of cord blood transplantation (CBT) in children in Spain. METHODS: Twenty-eight patients (mean age 6.5 years; mean weight 25 kg) received a CBT between July 1994 and May 1998 in several centres of the Spanish Pediatric Bone Marrow Transplant Group. In 2 patients the donor was an identical human leukocyte antigen (HLA)-sibling and in two the donor was a mismatched family donor. In 24 patients the donor was unrelated, and 21 of these received an HLA-mismatched CBT. Twenty-one patients (75 %) received a CBT for leukemia mainly in advanced phase. Seven patients were transplanted for genetic disease. Of these, five had congenital immunodeficiency. The conditioning treatment included total body irradiation in ten patients and combined chemotherapy in the remaining patients. In all patients graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine, and corticosteroids or methotrexate were added in patients with HLA-mismatched donors. The mean number of nucleated cells infused was 53.4 x 106/kg. RESULTS: Graft failure was observed in nine patients. Eighteen patients (64.3%) developed grade IIIV acute GVHD. Eight patients (28.6%) developed severe GVHD. Actuarial event free survival (EFS) of all the patients was 34.4 +/- 9% at 3 years, with a mean followup of 16.6 months. EFS was more favorable in patients with genetic disease (71>=6 17%) and in those with an HLA (A, B and DR) identical donor (6/6) (66>=6 19%). CONCLUSIONS: The most favorable results were obtained in patients with genetic diseases. We observed an inverse correlation between EFS and patients with HLA identical donors. The high incidence of severe acute GVHD could have been related to a lack of accuracy in the HLA typography of some patients.

[Allogeneic bone marrow transplantation in children with severe acquired aplastic anemia. The long-term results. The Spanish Group for Bone Marrow Transplantation in Children (GETMON)]. / Transplante alogénico de médula ósea en niños con aplasia medular grave adquirida. Resultados a largo plazo. Grupo Español para el Trasplante de Médula Osea en Niños (GETMON).

OBJECTIVE: The objective of this study was to evaluate retrospectively the efficacy of allogeneic BMT in the treatment of childhood severe acquired aplastic anemia (SAAA). PATIENTS AND METHODS: Twenty-seven children aged 2 to 16 years (median 11 years) received a BMT from an HLA identical sibling. Conditioning consisted in irradiation (total, nodal or thoraco-abdominal) plus cyclophosphamide (120-200 mg/kg) in 15 patients and cyclophosphamide alone (200 mg/kg) in the rest. Prophylaxis for graft-versus-host disease (GVHD) was cyclosporine and methotrexate in most patients. RESULTS: Twenty-four children achieved the bone marrow graft at a median of 18 days (neutrophils) and 21 days (platelets). Two patients failed engraftment and 1 had a late graft rejection. Three patients developed acute GVHD grades 3-4 and six chronic GVHD, which was extensive in 4 of them. Twenty patients/71%) are alive and disease-free at a median follow-up of 110 months and the estimated disease free survival at 6 years is 67%. CONCLUSIONS: Our results confirm that allogeneic bone marrow transplantation from an HLA identical sibling is the best treatment modality for children with SAAA. Acute GVHD associated with infections and graft rejection were responsible for treatment failures.

[Preoperative and postoperative chemotherapy of osteogenic sarcoma of the limbs in children]. / Tratamiento del sarcoma osteogénico de extremidades en la infancia con quimioterapia pre y postoperatoria.

BACKGROUND: A preoperative and postoperative chemotherapy regimen was applied to nonmetastatic osteosarcoma of the extremities in patients under 16 years of age to prevent the progress to metastatic disease and reduce the volume of the primary tumor in order to assess a conservative surgery. PATIENTS AND METHODS: A modified T-10 chemotherapy regimen was used before surgery, including high dose methotrexate, vincristine, bleomycin, cyclophosphamide and dactinomycin. After surgery patients with a grade of tumor necrosis > 90% received the same regimen up to 45 weeks of treatment. For the cases with necrosis < 90%, this regimen was substituted by adriamycin and cisplatinum. Survival was studied in relation with age, sex, tumor site, levels of alkaline phosphatase and LDH, surgical treatment and tumor necrosis in the surgical specimen after preoperative chemotherapy. Uni and multivariate analysis were performed. RESULTS: Twenty seven patients with ages ranging from 5 to 15 years (median 11 years) were treated. The most common site of primary tumor was femur, followed by humerus and tibia. In 9 cases (33%) tumor necrosis was > 90%. Consecutive surgery was performed in 20 patients and 7 suffered amputation or disarticulation of the extremity. Twenty patients remain alive and disease-free at a median follow-up of 84 months. The probability of disease-free survival at 50 months is 71%. The only factor which influenced significantly the survival was the grade of tumor necrosis. Survival was 100% for the 9 patients with necrosis > 90% and 53% for the 18 cases with necrosis > 90% (p = 0.022). CONCLUSIONS: Preoperative and postoperative chemotherapy achieve disease-free survival in more than two thirds of patients with nonmetastatic osteosarcoma of the extremities and allow a non mutilating surgical treatment in the majority of them.

[Allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia]. / Trasplante de medula ósea alogénico en niños con leucemia linfoblástica aguda.

PURPOSE: Long disease-free survival can be achieved with chemotherapy in over 50% of children with acute lymphoblastic leukaemia (ALL). However, those children suffering relapse or presenting with poor-risk features at diagnosis have scarce possibility of doing well with conventional chemotherapy. Bone marrow transplantation (BMT) is a good choice in such cases. MATERIAL AND METHODS: Between July 1985 and January 1992, twenty-four children with ALL underwent BMT in the Service of Pediatrics of the Hospital Ramón y Cajal. In seven patient with poor-risk criteria at diagnosis BMT was performed in the first complete remission (CR) and in seventeen cases it was performed after the second CR. The conditioning for transplantation consisted of cyclophosphamide plus total body irradiation in 21 patients and cyclophosphamide plus busulphan in 3 others. RESULTS: Fifteen patients persist in CR with post-transplant follow-up of 3 to 73 months (median, 31 months). Five patients died due to complications of the transplantation techniques, and four others died upon leukaemic relapse. The probability of disease-free survival for all cases is 61%, a plateau being reached at 13 months (83% and 52% for BMT in first or second CR, respectively). CONCLUSIONS: These findings confirm the efficacy of BMT in the treatment of children with ALL in second CR, or in first CR when there are very poor risk criteria at diagnosis.

[Bone marrow transplantation in malignant diseases in childhood using reverse isolation technics: evaluation of results]. / Trasplante de médula ósea en enfermedades malignas en la edad pediátrica con aislamiento inverso convencional: valoración de resultados.

Between July 1985 and March 1990, 31 pediatric patients with neoplastic diseases underwent bone marrow transplantation (22 allogenic and 9 autologous). Routine reverse isolation techniques with sterilization of the gastrointestinal tract were used in all cases. Of these patients, 55% had fever and 32% had a documented infection. In allogenic bone marrow transplants, 23% developed graft-versus-host disease, grade I-IV. The incidence of infection and graft-versus-host disease compares favorably with other published reports from centers utilizing laminar air flow rooms during bone marrow transplantation. This suggest that standard reverse isolation techniques may be used without increasing the morbidity and mortality in these patients.

[Autoimmune hemolytic anemia associated with severe giant cell hepatitis]. / Anemia hemolítica autoinmune y hepatitis severa con transformación giganto celular.

Autoimmune hemolytic anemia and severe giant cell hepatitis is an very uncommon association. Two patients aged 5 months and 2 years developed severe anemia, jaundice, hepatomegaly and splenomegaly. Laboratory tests demonstrated autoimmune hemolytic anemia and elevated amino-transferases. Diffuse giant cell transformation and distorted architecture was seen in liver biopsy. One patient had a cytomegalovirus infection. Early steroid therapy did not prevent fatal course with liver failure in one patient.