Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.

Clinical characteristics and evolution of hematological patients and COVID-19 in Argentina: a report from the Argentine Society of Hematology.

Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in patients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.

El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RTPCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.

[Autoimmune-alloimmune neonatal neutropenia. Serum reactive IgG and neutrophil-specific phenotype detected by flow cytometry]. / Neutropenia inmune-aloinmune neonatal. IgG sérica reactiva y fenotipo específico de los neutrófilos evaluados por citometría de flujo.

Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). They were evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established for serum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of different individuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensity of the patient's serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes were determined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Two maternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes were detected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility was detected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+.

Clinical characteristics and evolution of hematological patients and COVID-19 in Argentina: a report from the Argentine Society of Hematology / Características clínicas y evolución de pacientes hematológicos y COVID-19 en Argentina: datos de la Sociedad Argentina de Hematología

Abstract Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in pa tients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.

Resumen El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RT-PCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.

Neutropenia inmune - aloinmune neonatal IgG serica reactiva y fenotipo especifico de los neutrofilos evaluados por citometria de flujo / Autoimmune-alloimmune neonatal neutropenia. Serum reactive IgG and neutrophil-specific

La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con losneutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna alos antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20) en reacción autóloga(suero y células de un mismo individuo) y heteróloga (suero y células de diferentes individuos). Los resultadosse expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilucióndel suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune

Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). Theywere evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established forserum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of differentindividuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensityof the patient’s serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes weredetermined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Twomaternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes weredetected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility wasdetected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+