Arturo Muñoz

Prognosis of child recipients of hematopoietic stem cell transplantation requiring intensive care.

Abstract Objective. To determine prognostic factors in child recipients of hematopoietic stem cell transplantation from blood or bone marrow (BMT) requiring critical care. Design. Retrospective study of a cohort of patients. Setting. Pediatric Intensive Care Unit (PICU) in a university tertiary care center. Patients and participants. Child recipients of BMT requiring PICU admission. Measurements and results. Of the 151 children receiving transplants in our institution, 44 (29.1%) had 49 admissions to the PICU. Mechanical ventilation (MV) was required in 34 patients (69.4% of all admissions). Overall mortality was 31/44 (70.4%). Mortality in patients requiring MV and not requiring MV was 26/34 (76.5%) and 5/10 (50%), respectively. The following variables were significantly associated with mortality in the univariate analysis: male gender (P=0.02), older age (P=0.03), acute graft versus host disease (aGVHD) grades III or IV (P=0.01), severe hemorrhagic cystitis (P=0.01), the diagnosis of lung injury (P=0.04), the need for MV (P=0.03) or for renal replacement therapy (P=0.02), the presence of respiratory (P=0.003), cardiovascular (P=0.009) or gastrointestinal (P=0.01) failures, and the failure of ≥3 organs (P=0.01). In the multivariate analysis, the presence of aGVHD grades III or IV, male gender, severe hemorrhagic cystitis, and the failure of ≥3 organs were found to be independent predictors of mortality. Conclusions. The need for intensive care is common among child recipients of a BMT. These patients have a high mortality rate but some complications are reversible with critical care support. Certain clinical parameters are useful to establish a realistic prognosis and to optimize the use of the available resources.

High Survival Rate in Infant Acute Leukemia Treated With Early High-Dose Chemotherapy and Stem-Cell Support

PURPOSE Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy. It is still unknown if stem-cell transplantation (SCT) can improve the outcome of these patients. In the present study, we review our experience with SCT in infant acute leukemia to clarify this issue. PATIENTS AND METHODS We report the results of 26 infants who were submitted to a SCT for acute leukemia. There were 15 cases of acute myeloid leukemia and 10 cases of acute lymphoid leukemia. One patient had a bilineal leukemia. Twenty-two patients were in their first complete response (CR1), three were in their second CR, and one was in relapse. Eight patients were submitted to allogeneic SCT, and 18 underwent autologous SCT. RESULTS With a median follow-up of 67 months, the 5-year overall survival and disease-free survival (DFS) are 64% (SE = 9%) and 63% (SE = 10%), respectively. Autologous and allogeneic SCT offered similar outcome. There was not any transplant-related mortality, and all deaths were caused by relapse in the first 6 months after SCT. In multivariate analysis, the single factor associated with better DFS was an interval between CR1 and SCT of less than 4 months (P: <.025). CONCLUSION SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity. This study suggests that SCT should be performed in CR1 in the early phase of the disease.

Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact

Background Fanconi anaemia (FA) is a rare syndrome characterized by bone marrow failure, malformations and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing agents such as diepoxybutane (DEB) or mitomycin C (MMC) is the ‘gold standard’ test for the diagnosis of FA. Objective To study the variability, the diagnostic implications and the clinical impact of chromosome fragility in FA. Methods Data are presented from 198 DEB-induced chromosome fragility tests in patients with and without FA where information on genetic subtype, cell sensitivity to MMC and clinical data were available. Results This large series allowed quantification of the variability and the level of overlap in ICL sensitivity among patients with FA and the normal population. A new chromosome fragility index is proposed that provides a cut-off diagnostic level to unambiguously distinguish patients with FA, including mosaics, from non-FA individuals. Spontaneous chromosome fragility and its correlation with DEB-induced fragility was also analysed, indicating that although both variables are correlated, 54% of patients with FA do not have spontaneous fragility. The data reveal a correlation between malformations and sensitivity to ICL-inducing agents. This correlation was also statistically significant when the analysis was restricted to patients from the FA-A complementation group. Finally, chromosome fragility does not correlate with the age of onset of haematological disease. Conclusions This study proposes a new chromosome fragility index and suggests that genome instability during embryo development may be related to malformations in FA, while DEB-induced chromosome breaks in T cells have no prognostic value for the haematological disease.

On the Thermodynamic Stability of α,ω-Alkanedithiols Self-Assembled Monolayers on Unreconstructed and Reconstructed Au(111)

A comparative study on the thermodynamic stability of the lying down (LD) and standing up (SU) phases of alpha,omega-butanedithiol (BDT) on unreconstructed (U) and on reconstructed (R) Au(111) surfaces is presented. The R surface is made of dithiol-Au adatom units. Density functional calculations (DFT) allow the estimation of the adsorption energy of the LD and SU BDT phases on both substrates. Surface free energies based on the DFT calculations show the coverage of the clean Au(111) surface by the LD phase, and the LD to SU phase transition as the chemical potential of the BDT molecule is increased. The LD and SU phases are more stable on R than on U substrates, suggesting that the Au(111) surface should reconstruct upon BDT adsorption. The stability analysis is extended to longer alpha,omega-dithiols. Results reveal that the LD to SU phase transition is favored as the hydrocarbon chain length of the dithiol molecule is increased. Changes in the hydrogen pressure affect the formation of the LD phase, while they have only minor effects on the LD to SU phase transitions. Our calculations explain the influence of the number of carbon atoms in the hydrocarbon chains, hydrogen pressure and dithiol pressure (or concentration) on dithiol adsorption, and phase transitions. This information is relevant to control the coverage, reactivity, and surface chemistry of the alpha,omega-dithiol self-assembled monolayers on Au surfaces.

ALLOGENEIC STEM CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROMES IN CHILDREN: A Report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)

Introduction: Experience with the use of allogeneic hemopoietic stem transplantation (AHSCT) in pediatric myelodisplastic syndrome (MDS) in Spain is reviewed. Methods and patients: Twenty-four children with MDS were analyzed retrospectively. Median age of the patients was 10 years. Twenty patients received a bone marrow graft and 4 an unrelated cord blood (UCB) transplant; 12 bone marrow grafts were from a matched related donor (MRD) and 8 from a matched unrelated donor (MUD). Conditioning regimen consisted of chemotherapy alone in 17 patients (busulfan and cyclophosphamide ± melfalan) Seven patients received TBI and cyclophosphamide. Results: Ten patients died from transplant-related toxicity and 4 had relapse or disease progression post-AHSCT. Nine patients are alive and event-free with a median follow-up of 120 months. EFS rate in the MRD group was 0.48 (SE 0.13) versus 0.25 (SE 0.12) in the MUD/UCB group (p =. 07). Lansky score in survivors is ≥90%. Conclusions: In this historical series of children with MDS, in spite of severe transplant–related toxicity, encouraging EFS outcomes have been achieved after AHSCT with good quality of life.

Bronchiolitis obliterans Organizing Pneumonia Associated with Evans Syndrome

The association of bronchiolitis obliterans organizing pneumonia (BOOP) with insulin-dependent diabetes mellitus (IDDM) and Evans syndrome (autoimmune pancytopenia) has not been reported previously. We describe the case of a 4-year-old child diagnosed with IDDM and Evans syndrome who presented malaise, fever and nonproductive cough for several months. The chest radiograph revealed several patchy alveolar opacities with peripheral and bilateral distribution and multiple hilar and mediastinal adenopathies. An open lung biopsy established the diagnosis of BOOP. During the follow-up over the next 7 years, the patient had chronic relapses in spite of corticosteroid treatment and developed restrictive lung disease.

Sarcoma de Ewing en la infancia: resultados terapéuticos a largo plazo

FundamentoHemos analizado los resultados terapéuticos obtenidos en pacientes pediátricos diagnosticados de sarcoma de Ewing en nuestro centro y la significación de los factures de riesgo al diagnóstico sobre la supervivencia.Pacientes y métodosEntre los años 1980 y 1995 han sido tratados 37 pacientes. Se consideraron factores de riesgo al diagnóstico la existencia de metástasis, volumen del tumor primario mayor de 100 ml y localización centro-axial del mismo.ResultadosCon una mediana de seguimiento de 9 años están vivos y libres de enfermedad 25 pacientes (67,56%) y la supervivencia actuarial libre de enfermedad es del 64,86%. Los pacientes sin metástasis tuvieron una supervivencia libre de enfermedad del 74,4 frente al 16,6% de los que presentaron metástasis (p < 0,001). Los enfermos con volumen tumoral mayor de 100 ml tuvieron una supervivencia libre de enfermedad del 49,8%; no hubo ningÚn fallecimiento en el grupo de volumen tumoral menor de 100 ml. La supervivencia libre de enfermedad para los pacientes con localización periférica del tumor fue del 66,8 frente al 63% de los de localización centro-axial, diferencia que no fue estadísticamente significativa. El grupo tratado con cirugía asociada a quimioterapia obtuvo una mayor supervivencia, sin diferencias estadísticamente significativas.Conclusionesa) El tratamiento multidisciplinario del sarcoma de Ewing permite una curación en torno al 70% de los casos, yb) la existencia de metástasis al diagnóstico y un volumen tumoral superior a 100 ml son los dos factores de riesgo que influyen de manera significativa en la supervivenciaAbstractPurposeTo analyze the therapeutic results obtained in pediatric patients with Ewing’s sarcoma diagnosed in our hospital and to assess the significance of risk factors at the time of diagnosis in survival.Patients and methodsThirty-seven patients were treated between 1980 and 1995. Metastatic disease, primary tumor volume greater than 100 ml and tumor localization in the pelvis or axis were considered to be risk factors at the time of diagnosis.ResultsMedian period of observation was 9 years; 25 patients (67.56%) are alive and without evidence of disease. Estimated event-free survival (EFS) rate was 64.86%. Patients without metastatic disease had an EFS rate of 74.4%, compared with a rate of 16.6% in those with metastatic disease (p < 0.001). Patients with tumor volume greater than 100 ml had an EFS rate of 49.8%. All of the patients with tumor volume smaller than 100 ml are still alive. The EFS of patients with tumors localized in the limbs was 66.8%, compared with a rate of 63% in those with pelvis-axis localization. This difference was not statistically significant. Survival was longer in the group treated with surgery and chemotherapy, but differences were not statistically significant.Conclusionsa) Multidisciplinary treatment of Ewing’s sarcoma yields an EFS of approximately 70%;b) metastatic disease at diagnosis and tumor volume greater than 100 ml significantly influence survival.