Expression of NK Cell Receptor Ligands on Leukemic Cells Is Associated with the Outcome of Childhood Acute Leukemia.

Acute leukemia is the most common malignancy in children. Most patients are cured, but refractory/relapsed AML and ALL are the first cause of death from malignancy in children. Maintenance chemotherapy in ALL has improved survival by inducing leukemic cell apoptosis, but immune surveillance effectors such as NK cells might also contribute. The outcome of B-ALL (n = 70), T-ALL (n = 16), and AML (n = 16) pediatric patients was evaluated according to leukemic cell expression of ligands for activating and inhibiting receptors that regulate NK cell functioning. Increased expression of ULBP-1, a ligand for NKG2D, but not that of CD112 or CD155, ligands for DNAM-1, was associated with poorer 5-year event-free survival (5y-EFS, 77.6% vs. 94.9%, p < 0.03). Reduced expression of HLA-C on leukemic cells in patients with the KIR2DL1/HLA-C*04 interaction was associated with a higher rate of relapse (17.6% vs. 4.4%, p = 0.035) and lower 5y-EFS (70.6% vs. 92.6%, p < 0.002). KIR2DL1/HLA-C*04 interaction was an independent predictive factor of events (HR = 4.795, p < 0.005) or death (HR = 6.731, p < 0.005) and might provide additional information to the current risk stratification. Children who carry the KIR2DL1/HLA-C*04 interaction were refractory to current chemotherapy treatments, including allogeneic stem cell transplantation; therefore, they should be considered as candidates for alternative biological therapies that might offer better results.

Hematopoietic stem cell transplantation in pediatric patients with thalassemia and sickle cell disease: An experience of the Spanish Working Group for Bone Marrow Transplantation in Children (GETMON). / Trasplante de progenitores hematopoyéticos en niños con ß-talasemia y enfermedad drepanocítica: experiencia del grupo GETMON.

BACKGROUND AND OBJECTIVES: A recently occurring increase of the prevalence of haemoglobinopathies, ß-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric hematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). MATERIAL AND METHODS: Retrospective review of patients undergoing HSCT in the GETMON units until 2015. RESULTS: A total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. CONCLUSIONS: The results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients.

Type III pleuropulmonary blastoma in a dicer1 germline mutation carrier: The management of residual lung cystic lesions.

Pleuropulmonary blastoma (PPB) is a rare malignancy of childhood. It often represents a manifestation of a hereditary tumor predisposition syndrome (DICER1 syndrome). Because of its malignant potential, surgical resection of cystic lung lesions is recommended in germline DICER1 mutation carriers. We present a case of a 3-year-old male child with type III PPB successfully managed with ifosfamide, vincristine, actinomycin-D, and doxorubicin (IVADo) chemotherapy and surgery. A heterozygous germline pR688X mutation of DICER1 gene was demonstrated. Six years after primary diagnosis, several small lung cysts remained stable without further therapy. The management of residual asymptomatic lung cysts represents a clinical challenge in these patients.

[Neurological complications in the population of children with leukaemia]. / Complicaciones neurológicas en población infantil con leucemia.

INTRODUCTION: Leukaemia is the most frequent type of cancer at the paediatric age. The cure rate is 80% with intensive chemotherapy, which improves survival but also often increases the frequency of adverse side effects, including those of a neurological nature. AIMS: To describe the frequency and characteristics of the neurological complications (NC) in patients with acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML), as well as to identify factors associated to their presence, neurological morbidity and survival rate. PATIENTS AND METHODS: A retrospective study was conducted of the NC present in patients with ALL and AML between 1997 and 2012 treated and followed up by the child onco-haematology unit. The following variables were analysed: demographic data, oncological diagnosis, treatment and NC. RESULTS: Altogether 157 patients were included, 145 without infiltration of the central nervous system at diagnosis and eight with infiltration (rate of NC of 14% and 12%, respectively). The most frequent NC were: neuropathies (31%), altered levels of consciousness (27%), convulsions (22%) and headache (12%). Forty per cent of the patients with NC presented sequelae but none of them died as a consequence of the NC. More NC were detected in the age group of children aged under 6 years with high-degree ALL, at higher levels of severity and in patients who had received a haematopoietic stem-cell transplant, all of them with statistically significant differences. CONCLUSIONS: Neurological complications are common in patients with acute leukaemia, especially in those at a high-risk stage (above all if they are under the age of 6 years) and with haematopoietic stem-cell transplant. The associated mortality rate is low.

TITLE: Complicaciones neurologicas en poblacion infantil con leucemia.Introduccion. La leucemia es el cancer mas frecuente en edad pediatrica. Su tasa de curacion es del 80% con quimioterapia intensiva, que mejora la supervivencia, pero que tambien aumenta la frecuencia de efectos adversos, incluyendo los neurologicos. Objetivos. Describir la frecuencia y caracteristicas de las complicaciones neurologicas (CN) en pacientes con leucemia aguda linfoide (LAL) y leucemia aguda mieloide (LAM), e identificar los factores asociados a su presencia, la tasa de morbilidad neurologica y la supervivencia. Pacientes y metodos. Estudio retrospectivo de las CN presentes durante el tratamiento y seguimiento de los pacientes con LAL y LAM entre 1997 y 2012 por la unidad de oncohematologia infantil. Variables analizadas: datos demograficos, diagnostico oncologico, tratamiento y CN. Resultados. Se incluyo un total de 157 pacientes, 145 sin infiltracion de sistema nervioso central al diagnostico y ocho con infiltracion (tasa de CN del 14 y 12%, respectivamente). Las CN mas frecuentes fueron: neuropatias (31%), alteracion del nivel de conciencia (27%), convulsiones (22%) y cefalea (12%). Un 40% de los pacientes con CN ha presentado secuelas, pero ninguno ha fallecido como consecuencia de la CN. Se han detectado mas CN en el grupo de edad menor de 6 años con LAL de alto grado, en niveles de gravedad mas altos y en pacientes que habian recibido trasplante de precursores hematopoyeticos, todas ellas con diferencias estadisticamente significativas. Conclusiones. Las complicaciones neurologicas son frecuentes en los pacientes con leucemia aguda, en especial en aquellos con estadio de riesgo alto (sobre todo si son menores de 6 años) y trasplante de precursores hematopoyeticos. La mortalidad asociada es baja.