RESUMEN
Reticular dysgenesis is a rare congenital disorder characterized by severe combined immunodeficiency and profound neutropenia, curable to date, only by bone marrow transplantation. This report describes the association of bilateral sensorineural deafness with this disease.
Asunto(s)
Sordera/congénito , Sordera/diagnóstico , Leucopenia/congénito , Leucopenia/diagnóstico , Enfermedades Linfáticas/congénito , Enfermedades Linfáticas/diagnóstico , Inmunodeficiencia Combinada Grave/congénito , Inmunodeficiencia Combinada Grave/diagnóstico , Timo , Audiometría , Trasplante de Médula Ósea , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Prueba de Histocompatibilidad , Humanos , Incidencia , Lactante , Recién Nacido , Recuento de Leucocitos , Leucopenia/sangre , Leucopenia/genética , Leucopenia/terapia , Enfermedades Linfáticas/sangre , Enfermedades Linfáticas/genética , Enfermedades Linfáticas/terapia , Masculino , Estudios Retrospectivos , Inmunodeficiencia Combinada Grave/sangre , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/terapiaRESUMEN
A two-year-old girl with thrombocytopenia-absent radii syndrome underwent transplantation of allogeneic bone marrow from her histocompatible sibling to correct her persistently low platelet count. Six years after transplantation, she has durable engraftment of allogeneic marrow and a normal platelet count that will allow her to undergo necessary corrective orthopedic procedures.
Asunto(s)
Trasplante de Médula Ósea , Radio (Anatomía)/anomalías , Trombocitopenia/cirugía , Preescolar , Femenino , Humanos , Recuento de Plaquetas , Síndrome , Trombocitopenia/sangreRESUMEN
Since 1979, a total of 17 patients with Wiskott-Aldrich syndrome have undergone allogeneic bone marrow transplantation at Memorial Sloan-Kettering Cancer Center. Eleven patients received marrow from either human leukocyte antigen (HLA) genotypically identical siblings (nine patients) or an HLA phenotypically identical parent (two patients). Six patients received marrow grafts from HLA-disparate parents. Cytoreduction was accomplished with busulfan and cyclophosphamide for the HLA-identical recipients and total-body irradiation followed by high-dose cytarabine therapy in the mismatched recipients. All 11 recipients of HLA-identical marrow had successful grafts, and 10 of 11 are alive and well 28 to 145 months after transplantation. One patient died 10 months after transplantation of chronic graft-versus-host disease and interstitial pneumonitis caused by cytomegalovirus. Only one of the six mismatched graft recipients survives, 52+ months after transplantation; the other patients have died of extensive chronic graft-versus-host disease (one patient), lymphoma (three patients), or progressive pancytopenia accompanying Candida sepsis (one patient). Thus bone marrow transplantation represents the treatment of choice in patients with Wiskott-Aldrich syndrome who have an HLA-identical donor. However, our approach for patients lacking a histocompatible family donor requires modifications to overcome allogeneic resistance and decrease the posttransplantation immunoincompetence in these patients.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Antígenos HLA/inmunología , Síndrome de Wiskott-Aldrich/cirugía , Adulto , Trasplante de Médula Ósea/métodos , Niño , Preescolar , Enfermedad Injerto contra Huésped/prevención & control , Prueba de Histocompatibilidad , Humanos , Lactante , MasculinoRESUMEN
Because several human hematopoietic growth factors have been identified and shown to be effective for treatment of congenital or iatrogenic neutropenias, and cord blood contains stimulatory activities for blood-forming cells, we postulated that identification of these factors and analysis of their regulatory role in normal neonates would provide a rationale for their use in treating neonatal infections associated with neutropenia. We studied the plasma levels of granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF, respectively) and the frequency of granulomonopoietic colony-forming cells (CFU-GM) in the umbilical cord blood of normal term neonates. Plasma growth factor levels were measured by a biologic assay. Circulating hematopoietic progenitors were assayed for colony formation with different recombinant growth factors used as exogenous growth stimulators. The cell cycle status of these progenitors was analyzed by the thymidine suicide technique. At birth the leukocyte count (mean +/- SD) was 11.0 +/- 3.9 x 10(9)L and the neutrophil count was 5.6 +/- 2.6 x 10(9)/L. The incidence of CFU-GM was significantly higher in umbilical cord blood than in normal adult peripheral blood (p less than 0.005) with up to 40% of the cells in S phase (less than 10% in normal adults). Plasma levels of G-CSF and GM-CSF at birth were 40.8 +/- 2.8 U/ml and 19.9 +/- 5.2 U/ml, respectively (normal adult plasma levels 2.5 +/- 1.5 U/ml for G-CSF and undetectable for GM-CSF). These high levels of G-CSF and GM-CSF in umbilical cord blood of normal neonates might play a role in maintaining adequate neutrophil production.
Asunto(s)
Factores Estimulantes de Colonias/sangre , Sangre Fetal/análisis , Granulocitos/citología , Sustancias de Crecimiento/sangre , Adulto , Recuento de Células Sanguíneas , Recuento de Células , División Celular , Femenino , Sangre Fetal/citología , Factor Estimulante de Colonias de Granulocitos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Recién Nacido , Interleucina-1/sangre , Macrófagos/citología , Masculino , Proteínas Recombinantes , Células Madre/citología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Cellular and humoral components of leukotaxis were studied serially in four male infants with severe combined immunodeficiency disease. Two of the four, both lacking B and T cells initially, had a significant defect in neutrophil and monocyte chemotaxis. The other two, who had a high number of immunoglobulin-bearing cells (B cells), did not have these cellular abnormalities. It contrast, defective generation of chemotactic factor following endotoxin activation was observed in all patients. The defects were corrected coincident with or soon after successful engraftment of either bone marrow or fetal tissues. The reported deficiencies may be another manifestation of the heterogeneity in SCID.