[Haemophagocytic syndrome: A common pathogenic mechanism of various aetiologies]. / Síndrome hemofagocítico: expresión de diversas entidades nosológicas.

INTRODUCTION: Haemophagocytic syndrome (HPS) is a rare syndrome characterised by the uncontrolled activation and proliferation of histiocytes and T cells, leading to a cytokines overproduction. There are two forms of HPS: primary and secondary. OBJECTIVE: To analyse patients diagnosed with HPS at the Oncohaematology Department, using HLH-94 and 2004 protocol diagnostic criteria. MATERIALS AND METHODS: Retrospective study of clinical files of patients diagnosed with HPS, analysing the following features: diagnostic criteria, variability in clinical presentation, aetiology, treatment and outcome. RESULTS: Twenty-two patients were diagnosed with HPS: 6 familial haemophagocytic lymphohistiocytosis (FHL), 11 HPS with evidence of infection, 3 HPS associated with malignant disease and 2 macrophage activation syndrome (MAS) in patients with Crohn's disease and Juvenile Idiopathic Arthritis. The onset of FHL was within 1 year of age in 83.3%, except for 1 patient who was adolescent (MUNC13-4 mutations). SYMPTOMS: All patients (100%) had fever at diagnosis, 18 (85%) hepatosplenomegaly, 7 (31%) lymphadenopathy, 5 (21%) pallor, 3 (14%) rash and 3 (14%) neurological symptoms. LABORATORY ANALYSIS: all patients (100%) had cytopenias at diagnosis, 20 (90.9%) hypertriglyceridaemia, 19 (86%) hyperferritinaemia, 17 (77%) elevated serum liver enzymes, and 9 (40%) hypofibrinogenaemia. Decreased or absent NK-cell activity was detected in all patients (100%). Haemophagocytosis was found more frequently in bone marrow; however, liver or lymph node biopsies were required in two patients to demonstrate this. OUTCOME: Of the ten patients (6 FHL, 3 Epstein-Barr virus-associated HPS and 1 MAS) treated with HLH-94 and 2004 protocols, six received a stem-cell transplant; of these, 2 with FHL had a favourable outcome. The remaining 12 patients received aetiological/supportive therapy, with complete remission in 83.3%. CONCLUSIONS: The diagnosis of FHL should be made before the age of 2 years. Advances in genetic studies allow the detection of early and late forms of FHL. Immunochemotherapy and stem-cell transplantation constitute the treatment of FHL and aetiological/supportive therapy of acquired haemophagocytic lymphohistiocytosis, except in severe forms.

State-of-the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation: a report on the expert meeting of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) in Baden, Austria, 29-30 September 2015.

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care. One of the most important risks of stem cell transplant survivors is infertility. As well as in the field of allo-HSCT also the field of reproductive medicine has achieved substantial advances to offer potential options for fertility preservation in both boys and girls. Access to these procedures as well as their financing differs significantly throughout Europe. As all European children and adolescents should have the same possibility, the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation organised an expert meeting in September 2015. This manuscript describes the recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who have to undergo an allo-HSCT.

[Transient neonatal myeloproliferative disorder in the absence of Down syndrome]. / Síndrome mieloproliferativo transitorio neonatal en ausencia de síndrome de Down.

Transient neonatal leukemia or transient neonatal myeloproliferative disorder is commonly associated with Down syndrome. It usually resolves spontaneously in 4-5 months. However, 25 % of patients will subsequently develop acute megakaryoblastic leukemia or myelodysplastic syndrome. It has seldom been described without constitutional anomalies and is even less frequent in twins. We present three phenotypically normal patients with this disorder. One of them was diagnosed because he presented blueberry muffin syndrome. Diagnosis was guided by pathological examination of the skin lesions. The other two patients were monochorionic triplets. Their bichorionic sister presented no hematological disorders. Constitutional chromosomal abnormalities were ruled out in all three patients. They received support treatment only without chemotherapy. The clinical course was favorable with disappearance of marrow and peripheral blastosis in 4-5 months. Follow-up of 18 and 19 months has not revealed any hematological disorders. Caution must be exercised before initiating chemotherapy in these patients. We discuss the differential diagnosis with congenital leukemia and the prognostic and therapeutic implications that this entails.

[Spectrum of primary immunodeficiencies in a tertiary hospital over a period of 10 years]. / Espectro de las inmunodeficiencias primarias en un hospital de tercer nivel en un periodo de 10 años.

INTRODUCTION: More than 200 primary immunodeficiencies (PID) have been described and about 60% present during childhood. Early diagnosis and treatment have been shown to improve patient outcome. AIM: Analysis of patients with a PID diagnosed in a paediatric tertiary care hospital-referral centre over a period of 10 years. PATIENTS AND METHODS: Medical records of all paediatric patients followed up in our unit were retrospectively reviewed. Clinical and epidemiological features, laboratory tests, therapy and outcome were analysed. RESULTS: One hundred and eighty nine patients were followed up in this period of time. Antibody disorders were the most common diagnosis. In our series, clinical presentation at diagnosis were: recurrent respiratory infections in selective IgA deficiency and common variable immunodeficiency (CVID) patients, failure to thrive and opportunistic infections (mainly viral infections) in patients with severe combined immunodeficiency (SCID), skin abscesses (Staphylococcus aureus, Serratia spp.) and complicated pneumonia (Aspergillus spp., Rhodococcus equi) in chronic granulomatous disease, congenital heart disease and consistent phenotype in 22q11 deletion syndrome, skin abscesses and ecthyma gangrenosum in severe congenital neutropenia and opportunistic infections and sepsis (Pseudomonas aeruginosa) in children with X-linked agammaglobulinaemia (XLA). Lymphoproliferative disorders were common in CVID. No malignancies were observed during this period. One patient with XLA developed chronic encephalitis. All patients with CVID and XLA were receiving immunoglobulin replacement therapy (8 intravenous and 14 (since 2006) subcutaneous route) and in all but two SCID patients, stem cell transplantation was performed. Outcome was good in most of them except 8 SCID (2 prior and 6 after transplantation), 3 Wiskott-Aldrich syndrome, 1 complete DiGeorge, 1 chronic granulomatous disease and 1 ataxia-telangiectasia patients who died during follow-up. CONCLUSION: The vast majority of patients included in this series presented with typical clinical features; therefore, basic knowledge of these entities in primary care and collaboration with hospital referral centres should allow a large number of PID in children to be diagnosed at an early stage, leading to proper treatment and monitoring, and therefore improvement of patient prognosis.

[Intracranial arteriovenous malformations in children and adolescents]. / Malformaciones arteriovenosas intracraneales en niños y adolescentes.

Six children, ranging in age from 5 years to 13 years, with a history of intracranial arteriovenous malformation were studied from 1980 to 1989. The more frequent clinical presentation was the intracranial bleeding. The brain angiography was performed on five patients who were all diagnosed with cavernous hemangioma the diagnosis was anatomopathologic. Three patients were treated with neurosurgery and two patients were treated with radiosurgery. Only one patient died after the operation and the other five had a satisfactory recovery.

[Granulocyte colony-stimulating factor in the newborn neutropenic patient]. / Factor estimulante de colonias granulocíticas en el recién nacido neutropénico.

OBJECTIVE: To assess the therapeutic effect of G-CSF in newborns with neutropenia. METHODS: Newborn with evidence of both peripheral neutropenia and decreased granulocytic precursors in tibial bone marrow aspirate were included in the study. G-CSF was perfused intravenously over 2 hours at dose of 10 micrograms/kg/day, during 4-8 days. CBC were obtained immediately before each dose of G-CSF. RESULTS: Neutropenia followed neonatal sepsis in four cases and maternal pre-eclampsia in three. Prior to treatment, peripheral blood granulocyte (PMNL) counts ranged from 420 to 1,073/mm3. Once G-CSF infusion was started, counts returned to normal within 24-48 hours. No adverse effects related to G-CSF administration were noticed. CONCLUSIONS: G-CSF induces a significant increase in peripheral PMNL counts in newborn with neutropenia, in the absence of significant toxic effects. Our date suggest a potential role for G-CSF in the prophylaxis and treatment of sepsis in the neutropenic newborn, although widespread recommendation must await further, controlled studies.

[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.