RESUMEN
Since more and more children survive allogeneic bone marrow transplantation (BMT), knowledge of acute and late complications becomes increasingly important. Besides the major complications [(opportunistic) infections, veno-occlusive disease, graft versus host disease, and recurrence of primary disease], acute and chronic renal insufficiency are significant post-transplant complications that may contribute to transplant-related mortality. To elucidate risk factors for acute and chronic renal insufficiency post BMT, we performed a prospective study of all 66 children who received a BMT in a 2-year period at our institution; 21% had acute renal insufficiency post BMT. Risk factors for acute renal insufficiency were veno-occlusive disease, high cyclosporin serum levels, and foscarnet therapy. Of surviving patients, 11% developed chronic renal insufficiency 1 year post BMT. Acute renal insufficiency was the sole predictor of chronic renal insufficiency. In contrast to studies in adults, we did not find total body irradiation to be a risk factor for chronic renal insufficiency. Future long-term studies are needed to assess incidence and morbidity of chronic renal insufficiency in children following allogeneic BMT.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Complicaciones Posoperatorias/epidemiología , Insuficiencia Renal/epidemiología , Insuficiencia Renal/etiología , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Adolescente , Presión Sanguínea/fisiología , Niño , Preescolar , Femenino , Humanos , Lactante , Fallo Renal Crónico/diagnóstico por imagen , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Glomérulos Renales/diagnóstico por imagen , Glomérulos Renales/fisiopatología , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Prospectivos , Insuficiencia Renal/diagnóstico por imagen , Factores de Riesgo , Linfocitos T/fisiología , UltrasonografíaRESUMEN
Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2-q12 as a fusion partner of the MLL gene. The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with an extremely poor prognosis. Our findings further suggest that fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine a proB-cell phenotype in infant leukemia.
Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Factores de Transcripción , Secuencia de Aminoácidos/genética , Secuencia de Bases/genética , Mapeo Cromosómico , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 4/genética , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Cariotipificación , Datos de Secuencia Molecular , Proteína de la Leucemia Mieloide-Linfoide , Homología de Secuencia de Ácido Nucleico , Factores de Elongación Transcripcional , Translocación Genética/genéticaRESUMEN
Accelerated telomere shortening has been proposed as a possible long-term risk of allogeneic bone marrow transplantation (allo-BMT). In this study we monitored telomere length in white blood cells (WBC), granulocytes, and naïve and memory CD4+ T lymphocytes in recipients of allo-BMT at long-term follow-up. Peripheral blood was collected from 10 allo-BMT recipients and donors at a median interval of 18 years after allo-BMT. Telomere length was determined using Southern blot analysis. Similar to results previously reported at short-term follow-up, a small difference in telomere length (0.1-0.3 kb) between recipients and donors was detected in WBC, granulocytes and naïve CD4+ T cells. Our data therefore provide no evidence for sustained telomere shortening in leucocytes, and render the possibility of long-term haematopoietic graft failure unlikely. In addition, we observed two phenomena that may be related to involution of the thymus. First, the number of naïve CD4+ T cells in the blood was significantly lower in recipients (0.4 x 10(9)/l) than in donors (0.7 x 10(9)/l) (P < 0.05). Second, telomeres in memory CD4+ T cells from recipients were on average 0.6 kb shorter than those from donors (P = 0.01). The latter may be related to the reported rapid peripheral expansion of memory T cells immediately after transplantation.
