Outcome and toxicities associated to chemotherapy in children with acute lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational screening.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood. Although intensive chemotherapy has improved survival in those patients, important side effects, including hyperbilirubinemia, are frequent. Gilbert syndrome (GS) is a frequent condition that causes a reduction in glucuronidation and intermittent hyperbilirubinemia episodes. This could provoke a greater exposure to some cytotoxic agents used in ALL, increasing the risk of toxicity. On the other hand, unexplained hyperbilirubinemia could lead to unnecessary modifications or even treatment withdrawals, which could increase the risk of relapse, but data regarding this in ALL pediatric population are scarce. METHODS: Retrospective study to analyze toxicity, outcome and treatment modifications related to GS in children diagnosed with ALL. RESULTS: A total of 23 of 159 patients were diagnosed with GS. They had statistically higher hyperbilirubinemias during all treatment phases (P < 0.0001) and a slower methotrexate clearance when it was administered during a 24-hr infusion at high doses (patients with GS: 74 hr ± 19 vs. patients without GS: 64 hr ± 8; P < .002). However, no relevant toxicity or delays in treatment were found in them. Finally, changes in treatment due to hyperbilirubinemia were only done in 5 patients with GS. CONCLUSIONS: Differences in outcome were not found in patients with GS. Universal screening for GS appears to be not necessary in pediatric patients with ALL. However, when hyperbilirubinemia is observed, it must be rule out in order to avoid unnecessary changes in treatment.

Multiplex real-time PCR for prompt diagnosis of an outbreak of human parainfluenza 3 virus in children with acute leukemia.

INTRODUCTION: Human parainfluenza virus type 3 (HPIV-3) causes significant morbimortality in immunocompromised patients. Outbreaks of severe pneumonitis have been previously described in this setting. MATERIALS AND METHODS: Retrospective observational study in children diagnosed with acute leukemia and a documented HPIV-3 infection in the context of a nosocomial outbreak occurred in a single center. RESULT: During summer 2012, an HPIV-3 infection was detected in six hospitalized children with acute leukemia. All the patients had respiratory symptoms and one of them suffered from parotitis. CONCLUSION: Early diagnoses using multiplex real-time polymerase chain reaction (PCR) let us control this outbreak. A phylogenetic analysis confirmed person-to-person transmission of a single HPIV-3 variant.

Immune tolerance induction in haemophilia A patients with inhibitors by treatment with recombinant factor VIII: a retrospective non-interventional study.

Immune tolerance induction (ITI) can overcome inhibitory factor VIII (FVIII) antibodies in haemophilia A patients receiving FVIII replacement therapy. The objective was to evaluate the use of sucrose-formulated, full-length recombinant FVIII (rFVIII-FS) for ITI therapy. Patients (<8 years at ITI start) with severe haemophilia A and a peak inhibitor titre >5 Bethesda units (BU) who underwent ITI with any rFVIII-FS dose for ≥ 9 months (or until success) were eligible for this retrospective study. Efficacy analyses included descriptions of ITI treatment regimens and outcomes; ITI success was determined solely at the discretion of the investigator. Safety analyses included assessment of adverse events. Of 51 enrolled patients, 32 [high dose (≥ 85 IU kg(-1) day(-1)), n = 21; low dose, n = 11] were eligible for analysis. ITI was successful in 69% (22/32) of patients (high dose, 66.7%; low dose, 72.7%) after a median of 1.4 years (range, 0.1-3.6 years). Influencing factors for ITI success were start of ITI <1 year after inhibitor detection and an inhibitor titre <10 BU at ITI start. All patients successfully tolerized with ITI continued to receive rFVIII-FS prophylaxis as maintenance therapy, with no inhibitor recurrence from the end of ITI until study enrolment. Use of rFVIII-FS for ITI was effective and well tolerated; success rates were similar to those in published studies.

[Protocol for the study and treatment of immune thrombocytopenic purpura (ITP). ITP-2010]. / Protocolo de estudio y tratamiento de la trombocitopenia inmune primaria (PTI-2010).

Primary immune thrombocytopenia (ITP), formerly known as immune thrombocytopenic purpura, is a disease in which clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of ITP in children based on current guidelines, literature review, clinical trials and member consensus. The primary objective was to lessen clinical variability in diagnostic and therapeutic procedures in order to obtain best clinical results with minimal adverse events and good quality of life.

Assessment of neutrophil activation in whole blood by flow cytometry.

Flow cytometry methods currently used for measuring neutrophil activation involve sample manipulation, which may result in cellular depletion and artifactual activation. To design a new methodology for measurement of neutrophil activation with minimal sample manipulation. Oxidative burst and CD 11b neutrophil expression were simultaneously assessed by a new no-lyse no-wash technique and a standard lyse-method in 10 pediatric patients with recurrent infections and two patients with chronic granulomatous disease (CGD). The new technique was based on nucleic acid staining to discriminate erythrocytes and debris without requiring physical separation. Both methods served equally to confirm or eliminate the diagnosis of CGD and leukocyte adhesion deficiency type 1. The values of baseline CD11b and oxidative burst obtained using the lysis method were significantly higher than those obtained by the no-lyse no-wash method. After activation, the lysis method resulted in higher neutrophil depletion (41%vs. 19%, P = 0.03). When compared with standard methods, neutrophil activation assessment by a no-lyse no-wash method resulted in lower neutrophil depletion and differences in oxidative burst and CD11b neutrophil values.

[Microangiopathic hemolytic anemia and thrombocytopenia. Thrombotic thrombocytopenic purpura]. / Anemia hemolítica microangiopática ytrombocitopenia. ¿Púrpuratrombótica trombocitopénica?

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) or Moschovitz' syndrome is rare and is even rarer in childhood. Clinically, it is characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. The etiology is still unknown, although different factors such as large von Willebrand factor multimers and prostacyclin have been implicated. The acute form is more frequent, and in most cases the course is fulminant if treatment is not initiated. Laboratory data typically reveal hemolytic anemia, with schistocytes on the peripheral smear, diminished serum haptoglobin, and thrombocytopenia. MATERIAL AND METHODS: We present the clinical cases of two children, aged 4 and 7 respectively, with TTP, but with different evolution and treatment. Evolution was favorable in both patients. The first child recovered spontaneously. In the second plasmapheresis was required and produced remission of all the symptomatology. Normality has been maintained for 36 and 24 months respectively, and the children have presented no clinico-biological alterations.

Anemia hemolítica microangiopática y trombocitopenia. ¿Púrpuratrombótica trombocitopénica? / Microangiopathic hemolytic anemia and thrombocytopenia. ¿thrombotic thrombocytopenic purpura?

La púrpura trombótica trombocitopénica (PTT) o síndrome de Moschcovitz es un síndrome clínico poco frecuente, menos incluso en la edad pediátrica que en la adulta. Clínicamente se caracteriza por la presencia de anemia hemolítica microangiopática, trombocitopenia, sintomatología neurológica, fiebre y afectación renal. Su etiología es aún desconocida, aunque se han relacionado diferentes factores como los multímeros de factor Von Willebrand y la prostaciclina (PGI2). Es más frecuente la forma aguda de la enfermedad, y en la mayoría de los casos el curso es rápido y fulminante si no se inicia tratamiento. Los datos de laboratorio muestran típicamente una anemia de características hemolíticas, con abundantes hematíes fragmentados o esquistocitos, disminución de la haptoglobina y plaquetopenia. Se presentan los casos clínicos de 2 niños, de 4 y 7años respectivamente, con cuadro clínico compatible con PTT, pero con evolución y necesidades terapéuticas diferentes. La evolución de los pacientes fue buena. En el primer caso el cuadro remitió de forma espontánea y en el segundo caso precisó de plasmaféresis, con lo que desaparecieron los síntomas. La normalidad se ha mantenido durante 36 y 24 meses, respectivamente, y no han vuelto a presentar ninguna alteración clinicobiológica (AU)