[Ovarian cryopreservation in girls with cancer: new challenges]. / Criopreservación ovárica en niñas con cáncer: nuevos retos.

BACKGROUND: Ovarian cortex cryopreservation (OCC) for future autotransplant represents a treatment alternative for those paediatric cancer survivors affected of ovarian failure and fertility disorders. METHODS: Patients with high gonadotoxic risk are included in the Oncology Paediatric Fertility Preservation Programme: those receiving pelvic radiotherapy, bone marrow transplantation, high doses of cranial radiotherapy or alquilating agents, or those with bilateral ovarian pathology. Prior to the oncological treatment, the ovarian tissue is harvested laparoscopically. At the same time, other invasive procedures are done. Once malignancy is ruled out of the specimen and the presence of primordial follicles is confirmed, the multidisciplinary team of oncologist, paediatric surgeon and fertility specialist coordinate the processing and delivery of the ovarian cortex to the Comunidad Valenciana Tissue Bank. RESULTS: From July 2008 to May 2010 eight patients have been included in the programme, aged between 8-18 years old and with diagnosis of: Hodgkin's lymphoma (n= 2), Acute Myeloblastic and Lymphoblastic leukaemia (n= 2), pelvic Ewing's sarcoma, bilateral ovarian Teratoma and Meduloblastoma. Five patients underwent non gonadotoxic chemotherapy before OCC. Six additional procedures were done using the same anaesthetic event. Partial oophorectomy was performed in half the cases, total oophorectomy in the rest of them, and an ovarian pexia was once associated. All taken samples were found to be valid. CONCLUSIONS: OCC of selected patients was performed safely, with neither postoperative complications nor delay of the oncological treatment. Therefore, the first national experience in this procedure has been satisfactorily achieved.

Synovial sarcoma in children. A single centre experience.

Synovial sarcoma (SS) is a rare disease in the paediatric population, predominating in adolescents. Surgery remains the best treatment strategy for resectable cases. Adjuvant chemotherapy or radiotherapy can be used but have not proven efficacy. Metastatic disease and unsuccessful surgery are major prognostic factors. We describe four cases in children aged 7-13 years old. All of them were affected by SS of upper and lower limbs, and had satisfactory resections with different outcomes in spite of receiving diverse chemotherapy regimens. One of them is at the moment under treatment for relapse, two are disease-free and another died after metastatic disease.

[Renal tumors in infants aged less than 1 year]. / Tumores renales en niños menores de un año.

OBJECTIVE: To determine the frequency and distribution of primary renal tumors diagnosed in a pediatric oncology unit in children younger than 1 year and identify their clinical and histopathological characteristics, the treatment used, and outcomes. MATERIAL AND METHODS: We retrospectively reviewed the medical records of infants with primary tumors of the kidney diagnosed between January 1972 and February 2003. RESULTS: A total of 137 tumors were diagnosed in our unit during the period studied. Of these, 25 (18.2 %) occurred in infants aged less than 1 year. There were 17 boys and 8 girls. The most prevalent tumor in this age group was Wilms' tumor (WT) in 15 patients, followed by mesoblastic nephroma (MN) in 9 patients and rhabdoid tumor in 1 patient. The mean age at diagnosis of WT was 4.8 months (range: 1 day-11 months), with a median of 5.03 months. The median age at diagnosis of MN was 1 day (range: 1 day-3 months). Presenting symptoms consisted of abdominal mass in 20 patients, hematuria in 4 patients and intestinal pseudo-occlusion (MN) in 1 patient. High blood pressure was found in 12 of the 25 patients. Among the 15 WT, 9 were stage I, 1 was stage II, one was stage III, 2 were stage IV, and 1 was stage V. One patient died before surgery. Overall survival at 5 years was 0.67 (SE 0.12) for WT and 0.89 (SE 0.1) for MN, respectively, with a mean follow-up of 290 months. CONCLUSIONS: MN was more frequent than WT in infants aged less than 6 months. The first-line therapy in these patients is surgery since this type of tumor shows little chemosensitivity and chemotherapy is poorly tolerated in infants.

[Genomic profile in high risk neuroblastoma by comparative genomic hybridization]. / Perfil genómico del neuroblastoma de alto riesgo mediante hibridación genómica comparada.

Different subtypes of neuroblastoma (NB) carry associated genetic aberrations that predict their clinical course. Whole chromosome gains are usually associated with early clinical stages and good prognosis, while 1p deletion, 17q gain and MYCN amplification (MNA) are related to advanced stages and poor prognosis. High-risk neuroblastomas (NB-HR) include NB in children aged more than 1 year old, either stage 4 or any stages showing MNA except stage 1. The prognosis of NB-HR patients remains poor, despite aggressive therapy. Only MNA confers poor prognosis. Between January 2000 and February 2005, tumoral specimens from 60 patients with NB-HR were sent to the Spanish Reference Center for NB biological studies. In all cases, MYCN together with 1p36 status was analyzed by fluorescence in situ hybridization (FISH). Comparative genomic hybridization (CGH) was performed in 24 cases. Using FISH we detected 31 MNA cases including 29 with 1p36 deletion; there were 21 cases without MYCN amplification (MNNA) but 7 of these had 1p36 deletion; 8 cases showed MYCN gain (MNG) but 6 of these had 1p36 deletion. CGH showed other chromosomal alterations. Of 11 MNA cases, none had 11q loss and all of them showed 17q gain or 17 disomy. Of the 7 MNNA cases, there were 4 with 11q loss including 2 with 3p loss and all presented 17q gain or 17 disomy. The 6 MNG cases included 4 cases with 11q loss and 5 cases with 17q gain or 17 disomy. Genomic profiling by CGH in NB-HR confirms the interaction among genetic alterations, the prognostic significance of which should be evaluated to establish new treatment criteria.

[Attention process training application within an intervention project on attentional processes in children with cancer]. / Aplicacion del Attention Process Training dentro de un proyecto de intervencion en procesos atencionales en niños con cancer.

INTRODUCTION: Childhood cancer treatments have made a spectacular advance in recent years, obtaining survival rates of about 70%. These survival rates have permitted many children to reach adulthood, but also involve the appearance of previously unknown neurocognitive sequelae because of high mortality. DEVELOPMENT: Neuropsychological evaluation allows the detection of these deficits and the design of intervention. In children, rather than a loss of function there is a loss of the capacities that should develop in comparison with his/her peers. To obtain a base line to determine the affected and altered areas, it is equally vital to assess the acute and long term effects so as to evaluate the success of the intervention program. Attention Process Training (APT) is an individualized application program of attentional exercises of varying complexity in sustained, selective, alternating and divided attention. This program combines methods and techniques of cerebral damage rehabilitation, as well as educational and clinical psychology. It is completed with a self instruction training which is applied in situations of daily life. CONCLUSIONS: Child cancer treatment continues to carry long term neurocognitive sequelae. Neuropsychological evaluation is basic for its detection, allowing relevant information to be offered to parents and teachers, so as to facilitate design of individualized rehabilitation procedures. Attention training is basic for this type of population with generalized damage related to white matter, and forms part of a wider rehabilitation process that enhance the ecological validity of the program.

[Acute lymphoblastic leukemia of standard risk: preliminary results obtained with protocol LL-IV-81]. / Leucemia linfoblástica aguda de riesgo estándar: resultados preliminares del protocolo LL-IV-81.

Forty-five patients with acute lymphoblastic leukemia of standard risk who were treated with the same protocol of therapy are presented. Induction therapy consisted of Vincristine (5 doses), L-asparaginase (10 doses) and prednisone. Complete remission was attained in 43 cases (95%). Two different methods of CNS prophylaxis were used; radiotherapy of the skull (18 Gy) associated with intrathecal methotrexate and intermediate dose intravenous methotrexate (1 g/M, 12 dose) with simultaneously intrathecal methotrexate. With a mean follow-up time of 28 months in group A and 35 Mo in group B, 82% and 75% respectively remain in continuous complete remission (p: NS). One case of meningeal leukemia was detected in each group. There patients in group A (13.6%) and four in group B (20%) suffered a bone marrow relapse. Actuarial survival rate at 36 months were 76 among the patients in group A and 83% in group B. Our results indicate that the two methods of CNS prophylaxis are both effective and in this series we have not observed any decrease in the bone marrow relapse rate when intermediate dose methotrexate was used.

[Granulocyte recovery and early infection complications in oncologic pediatric patients treated with hematopoietic stem cell transplantation]. / Prendimiento de la serie blanca y complicaciones infecciosas precoces en pacientes oncológicos pediátricos sometidos a transplante de precursores hematopoyéticos.

OBJECTIVE: Infections during the early post-BMT period are a major cause of morbidity in BMT recipients. We report our experience in a single institution. PATIENTS AND METHODS: Clinical reports from all BMT patients between 1989-1995 were reviewed retrospectively. Routine reverse isolation techniques, prophylactic measures and central venous catheter were used in all cases and starting in 1992, G-CSF was also used. Fever in the aplasia period was considered a sign of infection. RESULTS: Sixty-three BMTs were performed between 1989 and 1995 with 30 being ABMT, 17 allogenic and 16 PBSC. The time for granulocyte recovery was shorter in PBSC + G-CSF patients (d + 11). There were 65 infections in the early post-BMT period: 22 were microbiologically confirmed, 18 of them being of bacterial origin and 14 disseminated. Gram positive bacteria were predominant. There were 6 cases of interstitial pneumonitis, with 3 of them being lethal. Infection-related mortality was 6.3%. CONCLUSIONS: 1) BMTs can be safely performed using conventional reverse isolation. 2) The use of PBSC and G-CSF accelerates granulocyte recovery in BMTs. 3) Infections due to Gram positive bacteria were a major cause of morbidity in our series. 4) Pneumonitis and fungal infections are the most frequent lethal infections in our patients.

[Non-Hodgkin's lymphoma in childhood: 19-year experience in a pediatric oncology unit]. / Linfomas no Hodgkin en la infancia: 19 años de experiencia en una unidad de oncología pediátrica.

Ninety-one patients with Non-Hodgkin's Lymphoma (NHL) were treated in our Pediatric Oncology Unit during a 19 year period. The median age at diagnosis was 5.8 years and there was a higher incidence in males. All patients were classified according to Murphy's stages and Rappaport's modified classification. Advanced disease and non-lymphoblastic histology were prevailing. Chemotherapy was the preferred treatment. Forty-seven patients (54%) are alive with a median follow-up period of 6.2 years. Actuarial survival rate at 5 years is 0.6. Advances in chemotherapy led to an increase in NHL patient's survival. Twenty patients died because of the disease and 21 because of fatal complications.

Scale for assessing quality of life of children survivors of cranial posterior fossa tumors.

BACKGROUND: Evaluation of quality of life of survivors of brain tumors is an important aspect of outcome that must be included in clinical studies. METHODS: We have developed a new scale for assessing quality of life (QL) of pediatric long-term survivors of posterior fossa tumors based on their physical, psychointellectual, and endocrine/growth status. We have studied 39 patients, with a median follow-up of 9 years. Twenty-five had cerebellar astrocytoma (CA), 6 medulloblastoma (MDB), 5 brain-stem glioma (BSG) and 3 ependymoma of IV ventricle (EPD). RESULTS: Sixty-six percent of children showed neurologic and/or visual sequelae. Little or no significant disability (Bloom's levels I-II) were present in 66%. Psychointellectual dysfunction was present in 44%, with an IQ < 90 in 39%. Endocrine and growth disorders were found in 26%, mostly stature anomalies. According to our scale, QL scores were high in 19 patients (49%), intermediate in 8 (20%), and low in the remaining 12 (31%). Unfavourable outcomes were related to age of less than 4 years, tumors other than CA (MDB, BSG, EPD), incomplete tumoral resection, and employment of radiotherapy and chemotherapy. CONCLUSION: Our results are comparable to others previously reported, and this supports the validity of our scale. We consider that this scale is applicable to evaluate QL of children survivors of cranial tumors.

[Systemic candidiasis in children with cancer]. / Candidiasis sistémicas en niños con cáncer.

Systemic fungal infections have long been recognized in terminally ill patients with cancer. Systemic candidiasis is the most common, the incidence having increased in the last few years. Eight children diagnosed as having systemic candidiasis during a two-year period (1987-1988) are presented. Three had an isolated fungal pneumonitis, two an hepatosplenic candidiasis, one a multisystemic involvement (hepatosplenic, pulmonary and nodular skin lesions) and the remaining two patients had a Candida sepsis with no visceral lesions having been documented. All patients had neutropenia and prolonged fever no responsive to broad spectrum antibiotics. We would like to underline the importance of an early and prolonged antifungal therapy, especially in hepatosplenic candidiasis, in order to obtain the cure.

[Down's syndrome and leukemia]. / Síndrome de Down y leucemia.

OBJECTIVE: Children with Down's Syndrome (DS) have a high risk for leukemia and need special clinical management. For this reason we have reviewed our experience. PATIENTS AND METHODS: All children with DS diagnosed a having acute leukemia during a 21-year period were reviewed retrospectively. Treatment was administered according to current protocols in our unit at the time of diagnosis without any initial modification. RESULTS: There were 13 children with DS and acute leukemia [6 ALL, 4 AML and 3 transient leukemias (TL)]. No patient presented CNS leukemia at diagnosis. All children with AML and DS were under three years of age and standard treatments did not achieve satisfactory results. TL regressed in two newborns without developing AMKL later. Five out of six patients with DS and ALL achieved complete remission. Currently, 4 of these children are alive and off therapy. Toxicities related to treatment were observed in almost all of the patients. CONCLUSIONS: Children with DS suffer a higher risk of developing leukemia. They should receive standard protocols, but aggressive supportive care might be provided as they have a higher incidence of treatment related toxicities. Prognosis of these children is similar or even better in some cases than children without DS. TL is a true neoplastic process capable of spontaneous remission and it can progress to AMKL.

[Acute lymphoblastic leukemia: clinical data and results of intensive chemotherapy]. / Leucemia no linfoblástica aguda: datos clínicos y resultados de una quimioterapia intensiva.

Twenty-one children, between eight months and twelve years old, diagnosed as having acute nonlymphoblastic leukemia (ANLL), were treated with an intensive chemotherapy based on a modified VAPA protocol. Complete remission rate was 80%, and the 5 year-survival rate is 46%. One chloroma, one central nervous system, and four bone marrow relapses were observed; all except the first having an unfavourable outcome. Significant risk prognostic factors in this series proved to be hepatomegaly (greater than 5 cm) and delay in obtaining remission. No fatal complications were observed.

[Retinoblastoma: multidisciplinary treatment in a group of 32 patients]. / Retinoblastoma: tratamiento multidisciplinario en una serie de 32 pacientes.

Thirty-two children with retinoblastoma (RTB) were treated in our oncology unit between September 1981 and October 1989. There were 18 unilateral RTB and 14 bilateral. The median age at diagnosis was 24 months. Leukocoria was the most common sign of presentation (66%). All patients were treated with a protocol based on Reese-Ellsworth classification and the anatomo-clinic extension. Thirty patients were enucleated (7 bilaterally), 14 of which needed coadjuvant chemotherapy and 6 orbital radiotherapy. Two patients died, one from each group. The disease-free survival rate is 90.6% with a medium follow-up of 43.5 months. Seven children went blind because of bilateral enucleation and seven present facial deformity caused by radiotherapy. We underline the importance of improving the effectiveness of conservative treatment in order to reduce the number of enucleation.

[Evaluation of a home care program for children with cancer]. / Evaluación de un programa de hospitalización a domicilio para niños con cáncer.

The home care team dependent from the pediatric oncology unit in our institution started working in April, 1997. We evaluate in this paper the medical activities accomplished in seventeen month experience. The team is constituted by a pediatric oncologist, two pediatric nurses and a clinical assistant with experience in the specialty. The geographic area we cover is la Communidad Valenciana. We directly attend children living in Valencia city and its metropolitan area. For the rest of patients, we coordinate the interventions of the local primary care teams and local hospitals. 127 patients have been admitted in the home care unit in 433 occasions. The immediate reasons for the admission were: early discharge from the hospital (61%), followed by the administration of antibiotics (18%) and chemotherapy (12%) at home. We attended 17 children in the terminal phase of their diseases. Five of them required opioid treatment for pain control. Six out of eight patients living in the area of direct intervention of the home care team died at home. The most common cause of discharge (73%) was the achievement of the goals planned when the patient was included in the program. Only in two cases (0.5%) we did not found enough cooperation from the parents and the treatment was completed in the hospital. This program has been well accepted by our patients and their parents and permits to shorten the stay in the hospital.

[Neuroblastoma in children under than 1 year of age]. / Neuroblastoma en niños menores de 1 año.

OBJECTIVE: Our objective was to carry out a prospective multicenter study of neuroblastoma patients diagnosed between 0 and 12 months of age. PATIENTS AND METHODS: Diagnostic procedures included histology, catecholamine excretion, bone marrow cytology and MIBG-scan. Staging was evaluated according to the INSS classification. After 1992, Simada criteria were used and also N-myc amplification, DNA index and P-glycoprotein determinations in tumoral tissue. The surgical technique employed and complications derived from it were also evaluated. The patients were treated according to stage with multicenter Spanish protocols N-I-87 and N-II-92. Overall survival and event free survival were calculated by actuarial methods. RESULTS: Between October 1987 and June 1992, a total of 140 infants less than one year of age were registered and diagnosed of neuroblastoma, representing 40% of all neuroblastoma cases. Median age was 0.3 years and 73% were less than 6 months of age at diagnosis. The most frequent stage was 1 (35%) followed by 4-S (20%). The frequency of unfavorable prognostic factors was the following: LDH (21%), NSE (14%), ferritin (18%), Shimada (7%), DNA (35%), NMA (3%), TrakA (23%), P-glycoprotein (19%). Surgery was performed in 133 children: total resection was reported in 94 and > 90% in another 22 cases. Complications attributed to surgery occurred in 12% of the cases. Chemotherapy was given in 73 cases and radiotherapy in 7. The five year total survival is 91% and the event free survival 88%. Survival by stages: Stage 1 = 91%, stage 2A = 88%, stage 2B = 100%, stage 3 = 84%, stage 4 = 56% and stage 4-S = 100%. CONCLUSIONS: 1) The majority of neuroblastoma cases in infants less than one year old are diagnosed before six months of age. 2) For this age group stages 1 and 4-S are the most frequently observed. 3) Unfavorable biological factors are less frequent than for children over one year of age and are associated with disseminated disease (advanced stage). 4) The outcome is excellent, except for stage 4 patients. The cases in stage 1 and 2 may be treated by surgery alone. Chemotherapy may be of benefit for stage 3 patients.