Early post-operative neurodevelopment and visual assessment in neonates with congenital heart disease undergoing cardiac surgery.

OBJECTIVE: Assessment of neurobehavior and visual function of newborns with congenital heart disease during the post-operative period to identify infants at risk of neurodevelopmental and visual impairment. STUDY DESIGN: Prospective study that included 45 newborns who underwent cardiac surgery. Newborn Behavioral Observations test (NBO) and "ML Battery of Optotypes" were used for assessment. RESULTS: The median NBO global score was 2.4 [2.1-2.6]. Total days of oral morphine [p = 0.005] and total days of sedation [p = 0.009] were strongly related to abnormal evaluations. Time of cerebral regional oxygen saturation (CrSO2) under 40% during surgery and increased lactate were related to abnormal motor evaluation. Only 14.5% of patients presented pathological results in visual evaluation. CONCLUSIONS: We have demonstrated alterations in attention, autonomic, motor, and oral motor function. Duration of sedative medication, time of CrSO2 under 40% during surgery, and increased lactate are the most important risk factors. No significant visual impairment was detected.

LUCAS (lung ultrasonography in cardiac surgery) score to monitor pulmonary edema after congenital cardiac surgery in children.

AIM: Cardiopulmonary bypass (CPB) generates a systemic capillary leak syndrome with pulmonary edema. Lung ultrasound (LUS) could be useful to monitor it. Primary objective was to compare sensitivity, specificity, positive and negative predictive values of chest X-ray and LUS to detect pulmonary edema using a new score (LUCAS). Secondary objectives were to evaluate correlation between LUCAS score and respiratory and inotropic support. METHODS: Prospective intervention study including patients <2 months admitted to the Pediatric Intensive Care Unit after CPB. LUS was performed with a lineal probe, screening 3 points in each lung (parasternal, anterolateral and posterior area), pre and post-CPB. Pulmonary edema was evaluated clinically, through LUCAS score and with X-ray. RESULTS: 17 patients were included. LUS achieved higher sensitivity than X-ray to detect pulmonary edema (91.7 versus 44.0%) and greater predictive negative value (88.2 versus 53.3%). There was correlation between higher LUCAS score prior to surgery and longer mechanical ventilation. High values of LUCAS score after surgery correlated with longer CPB time, inotropic support, and FiO2 need. CONCLUSION: LUS detected pulmonary edema better than chest X-ray, with greater sensitivity and negative predictive value. LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.Key notesCardiopulmonary bypass during cardiac surgery, generates a systemic capillary leak syndrome with pulmonary edema.In this prospective study performed in the Pediatric Intensive Care Unit, lung ultrasound detected pulmonary edema better than X-ray, with greater sensitivity and negative predictive value.LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.

Refractory Cardiogenic Shock due to Enterovirus Myocarditis: Experience at one Institution / Shock cardiogenico refractario secundario a miocarditis por enterovirus: experiencia en una institución

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miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.

Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment.

OBJECTIVES: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively. RESULTS: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

Ecografía torácica para guiar maniobras de reclutamiento pulmonar / Chest ultrasound for guiding lung recruitment maneuvers

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Área del corazón del Hospital Sant Joan de Déu / Heart Area of the Hospital Sant Joan de Déu

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Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders.

Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy was treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD.

BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.

Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB.

Análisis de la supervivencia de los niños con inmunodeficiencias primarias que han recibido un trasplante de progenitores hematopoyéticos en Espana / Survival analysis of hematopoietic stem cell transplantation in children with primary immunodeficiency in Spain

INTRODUCCIÓN: Los niños afectados de inmunodeficiencias primarias presentan infecciones graves y mayor prevalencia de manifestaciones autoinmunitarias, alergias y enfermedad linfoproliferativa. El trasplante alogénico de precursores hematopoyéticos ha sido el único tratamiento curativo durante décadas. PACIENTES Y MÉTODOS: Pacientes con inmunodeficiencias primarias que recibieron trasplante alogénico de precursores hematopoyéticos desde 1985 hasta 2011, recogidos en el Registro Nacional del Grupo Español para Trasplante de Médula Ósea en Niños. RESULTADOS: Ciento cincuenta y nueve niños recibieron un total de 173 trasplantes, 97 por inmunodeficiencia combinada grave, 30 por enfermedades de disregulación inmunitaria, 25 por síndrome de Wiskott-Aldrich y 21 por defectos de número y/o función de los fagocitos. La mediana de edad al diagnóstico fue de 6 meses (17 días-168 meses) y de 12 meses (1 mes-189 meses) al trasplante. Los donantes fueron hermano HLA idéntico en 30 (19%), donante familiar alternativo en 40 (25%) y donante no emparentado en 89 (56%). La fuente de progenitores fue médula ósea en 68 (43%), sangre de cordón umbilical en 52 (33%) y sangre periférica en 39 (24%). Permanecen vivos 98 niños (61,6%), 57 (35,9%) fallecieron. La supervivencia libre de enfermedad a los 10 años fue del 63, el 90% para los pacientes trasplantados de hermano HLA idéntico, el 36% para los trasplantados de un donante familiar alternativo y el 66 para los trasplantados de donante no emparentado

INTRODUCTION: Children with primary immunodeficiency have severe life-threatening infections and a higher prevalence of autoimmune problems, allergy and lymphoproliferative disorders. Allogenic hematopoietic stem cell transplantation has been the only potentially curative option. PATIENTS AND METHODS: Patients with primary immunodeficiency underwent allogenic stem cell transplantation in the period 1985-2011, and registered in the Spanish Working Party for Bone Marrow Transplantation in Children. RESULTS: One hundred and fifty nine patients underwent 173 allogenic stem cell transplantations, of whom 97 had severe combined immunodeficiency, 30 with immune dysregulation disorders, 25 Wiskott-Aldrich syndrome, and 21 phagocyte disorders. The median patient age at diagnosis was 6 months (range: 17 days - 168 months) and the median patient age at transplant was 12 months (range: 1 month - 189 months). The donors were 30 (19%) identical siblings, 40 (25%) alternative family donors, and 89 (56%) unrelated donors. The source of stem cells was bone marrow in 68 (43%), cord blood in 52 (33%), and peripheral blood in 39 (24%). Ninety eight (61.6%) are alive, 57 (35.9%) died. Event-free survival at 10 years was 63%, with 90% for children transplanted from identical siblings, 36% for those transplanted from alternative family donors, and 66% for those transplanted from unrelated donors. CONCLUSIONS: The best results have been obtained with identical siblings, but other options may be considered

[Survival analysis of hematopoietic stem cell transplantation in children with primary immunodeficiency in Spain]. / Análisis de la supervivencia de los niños con inmunodeficiencias primarias que han recibido un trasplante de progenitores hematopoyéticos en España.

INTRODUCTION: Children with primary immunodeficiency have severe life-threatening infections and a higher prevalence of autoimmune problems, allergy and lymphoproliferative disorders. Allogenic hematopoietic stem cell transplantation has been the only potentially curative option. PATIENTS AND METHODS: Patients with primary immunodeficiency underwent allogenic stem cell transplantation in the period 1985-2011, and registered in the Spanish Working Party for Bone Marrow Transplantation in Children. RESULTS: One hundred and fifty nine patients underwent 173 allogenic stem cell transplantations, of whom 97 had severe combined immunodeficiency, 30 with immune dysregulation disorders, 25 Wiskott-Aldrich syndrome, and 21 phagocyte disorders. The median patient age at diagnosis was 6 months (range: 17 days - 168 months) and the median patient age at transplant was 12 months (range: 1 month - 189 months). The donors were 30 (19%) identical siblings, 40 (25%) alternative family donors, and 89 (56%) unrelated donors. The source of stem cells was bone marrow in 68 (43%), cord blood in 52 (33%), and peripheral blood in 39 (24%). Ninety eight (61.6%) are alive, 57 (35.9%) died. Event-free survival at 10 years was 63%, with 90% for children transplanted from identical siblings, 36% for those transplanted from alternative family donors, and 66% for those transplanted from unrelated donors. CONCLUSIONS: The best results have been obtained with identical siblings, but other options may be considered.

Defecto diafragmático, cardiopatía congénita, agonadismo: un nuevo caso de síndrome de PAGOD / Diaphragmatic defect, congenital heart disease, agonadism: a new case of PAGOD syndrome

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Long-term outcome and prognostic factors of unrelated cord blood transplantation in children with haematological malignancies: a retrospective study using the Spanish Working Party for BMT in Children (GETMON) database.

Outcomes of unrelated cord blood transplants (UCBT) were assessed in 172 consecutive children, median age 5 years (range: 0.5-18), with haematological malignancies treated at nine Spanish hospitals between February 1996 and April 2009. Data were collected from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) database. ALL was diagnosed in 125 patients, AML in 43 and myelodysplastic syndrome in 4. Myeloid engraftment (ANC⩾0.5 × 10(9)/L) occurred in 87.2% at a median of 22 days and was associated with the total nucleated cell (TNC) dose infused and use of a TT-containing conditioning regimen. Cumulative incidence of relapse was 20% at 1 year post transplant and 29% at 3 years, being higher in patients with a diagnosis of ALL, very high risk disease and GVHD grades 0-1. Cumulative incidence of non-relapse mortality (NRM) was 19% at 100 days post transplant and 39% at 1 year. BU-FLU-TT-ATG-conditioned patients had lower NRM. Disease-free survival (DFS) was 40% at 2 years post transplant (for patients transplanted since 2006). On multivariate analysis, TNC dose infused, AML and BU-FLU-TT-ATG-conditioning regimen increased the probability of DFS. It is of paramount importance to select cord blood units with the highest cell dose. As the BU-FLU-TT-ATG-conditioning regimen was associated with better DFS owing to lower NRM, further prospective studies testing this regimen are warranted.

Servicio de Cuidados Intensivos Pediátricos del Hospital Vall d´Hebron: Diez años de soporte vital extracorpóreo / Pediatric Intensive Care Sevice of the Hosptial Vall d´hebron: Ten years of extracorporeal life support

La medicina intensiva se ha caracterizado desde sus inicios pro dar soporte no tanto a una patología específica sino al paciente que presenta fallo de la función de uno o varios órganos. Tradicionalmente, dicho enfoque ha consistido en optimiar la función de los órganos mediante el empleo de fármacos específicos (diuréticos, inotropos ... ) y de dispositivos mecániicos (ventilación mecánica). El cambio de paradigma de la última década consiste en pasar de apoyar al órgano enfermo a sustituir completamente su función, a la espera de la recuperación de la misma o bien de realización de un trasplante de ógano. Dicha sustitución de la función de órgano se inició en las Unidades de hemodiálisis, trasladándose después a las unidades de cuidados intensivos en forma de técnicas de depuración renal continua. Los desarrollos tecnológicos más recientes han permitido aplicar el mismo enfoque al fallo respiratorio y/o cardiaco refractarios mediante el empleo de la oxigenación con membrana extracorpórea y/o de los dispositivos de asistencia ventricular. La Unidad de Cuidados Intensivos Pediátricos del Hospital Vall d´Hebron inició su programa de Soporte Vital Extracorpóreo en el año 2002, habiendo superado en la actualidad el centenar de tratamietno con estas técnicas. La experiencia acumulada y los resultados actuales nos permiten afirmar que no encontramos en una nueva etapa en la que estas técnicas se han convertido en un cuidado estándar que ha transformado nuestra manera de afrontar la atención al niño críticamente enfermo (AU)

Intensive care medicine is characterized not by the care of a specific set of diseases but by treating those patients who present single or multiple organ failure. The trditional approach has been to optimize organ function by using specific drugs (diuretics, inotropes…) or mechanical devices (mechanical ventilation). During the last decade there has been a paradigmatic hange connsisting in substituting the function of the failing organ instead of trying to ameliorate it, until recovery ensues or an organ transplantation can be carried out. The concept of organ function substitution was introduced through haemodialysis in renal wardas and them brought to itnesive care units in the form of continuoud renal replacement therapy. The most recent technological improvements allow us to apply the same strategy to refractory cardiac and/or respiratory failure by means of extracorporeal membrane oxygentation and/or ventricular assist devices. The Extracorporeal Life Support Program at the Pediatric Intensive Care Unit of Vall d´hebron Hospital started in 2002, more than a hundred patints have been treated so far. The experience acquired and the msot recen outcomes attained allow us to state that these techniques have become a standard o care and that they have transformed the way we approach the care of the critically ill child (AU)

Resultados del trasplante de progenitores hematopoyéticos en hemoglobinopatías: talasemia maior y enfermedad drepanocítica / Results of hematopoietic stem cell transplantation in hemoglobinopathies: Thalassemia major and sickle cell disease

Introducción: La prevalencia de las hemoglobinopatías en nuestro medio ha aumentado como consecuencia de los flujos migratorios. La talasemia mayor cursa con anemia hemolítica crónica y necesidad de transfusiones regulares desde el año de vida. La enfermedad drepanocítica cursa con anemia, vasculopatía y daño orgánico progresivo. En ambas, la esperanza de vida está disminuida. El trasplante alogénico de progenitores hematopoyéticos es una opción de curación para estos pacientes. Pacientes: Diecisiete pacientes recibieron un trasplante alogénico de progenitores hematopoyéticos: 14 afectados de talasemia maior y 3 de enfermedad drepanocítica. Resultados: Los donantes fueron en los pacientes con talasemia mayor 9 hermanos HLA-idénticos, 2 progenitores con una diferencia antigénica HLA y 3 donantes no emparentados, y en aquellos con enfermedad drepanocítica, 3 hermanos HLA-idénticos. La fuente fue la médula ósea en todos, excepto uno. La media de edad al trasplante de progenitores hematopoyéticos fue de 6 años (intervalo: 1-16) en los niños con talasemia mayor y doce años (intervalo: 8-15) en los niños con enfermedad drepanocítica. Se confirmó injerto medular en todos los pacientes. Dos con talasemia mayor presentaron fallo de injerto secundario, precisando nuevamente soporte transfusional. Trece pacientes presentaron quimerismo completo y 2 quimerismo mixto, todos con normalización de la cifra de hemoglobina y sin requerimiento de transfusiones. Los pacientes con enfermedad drepanocítica no presentaron más episodios vasooclusivos y la funciones pulmonar y cerebral en aquellos pacientes que presentaban afectación en el momento del trasplante se estabilizaron. Tres pacientes con talasemia mayor desarrollaron enfermedad injerto contra huésped crónica y 5, hipogonadismo hipogonadotropo. Conclusiones: Nuestra experiencia confirma que el trasplante alogénico de progenitores hematopoyéticos de hermano HLA idéntico es una buena opción en el tratamiento de la talasemia mayor y la enfermedad drepanocítica. En el caso de la talasemia mayor, el trasplante de donante no emparentado es una opción terapéutica en centros especializados, ya que, a pesar de los buenos resultados presentados, la morbimortalidad de este procedimiento puede ser elevada, frente a la alternativa de un tratamiento médico no curativo pero con expectativas de supervivencia prolongada. En el caso de la enfermedad drepanocítica, el trasplante de donante no emparentado todavía está en fases preliminares de investigación (AU)

Background: The prevalence of hemoglobinopathies in Spain is increasing as a result of immigration. Thalassemia major presents with chronic hemolytic anemia that requires regular red blood cell transfusions within the first year of life. Patients with sickle cell disease suffer from chronic anemia, vasculopathy and progressive damage in almost any organ. There is decreased life expectancy in both conditions. Allogeneic hematopoietic stem cell transplantation represents the only potentially curative option. Patients: Seventeen patients (fourteen thalassemia major, and three sickle cell disease) underwent allogeneic hematopoietic stem cell transplantations. Results: In the thalassemia group, nine donors were HLA-geno-identical siblings, two were partially matched related donors (one HLA allele mismatch), and three unrelated donors. All three patients with sickle cell disease were transplanted from HLA-geno-identical siblings. The source of stem cells was bone marrow in sixteen cases. Median patient age at transplant was six years (range: 1–16) in the thalassemia group, and twelve years (range: 8–15) in the sickle cell disease group. The graft was successful in all patients. Secondary graft rejection was observed in two thalassemia patients rendering them dependent on blood transfusions. Complete chimerism was observed in thirteen patients and, although mixed chimerism occurred in two, with all of them showing normal hemoglobin levels after transplantation and not requiring further transfusion support. Patients affected by sickle cell disease did not present with new vaso-occlusive crises, and stabilization of pulmonary and neurological function was observed. Chronic graft-versus-host disease was detected in three patients affected by thalassemia, and hypogonadotrophic hypogonadism in five patients. Conclusions: We conclude that for thalassemia major and sickle cell disease, allogenic hematopoietic stem cell transplantation from HLA-geno-identical siblings offers a high probability of complication-free survival. Despite good results, morbidity and mortality associated with transplantation from unrelated donors is a risk that might be considered, in contrast to a non-curative medical treatment that offers a long term survival. For thalassemia major groups it could be an option, but not for sickle cell disease, which is still in the investigational phase (AU)