RESUMEN
BAT-25 and BAT-26 are mononucleotide microsatellites with quasi-monomorphic allele length distribution in healthy controls but unstable, shortened alleles in solid organ tumours with a mutator phenotype (RER+). Both markers are highly sensitive and specific for RER+ colorectal cancer. This study evaluated three mononucleotide microsatellites, BAT-25, BAT-26 and BAT-40 (a polymorphic mononucleotide microsatellite) in RER+ acute myeloid leukaemia (AML). Sixteen [six therapy-related AML (t-AML), 10 de novo AML] known RER+ AML, 22 healthy controls and five known RER- AML samples were analysed. In healthy controls and RER- AML, BAT-25 and BAT-26 were quasi-monomorphic and BAT-40 was polymorphic. Of the RER+ AML samples, 0 of 16 had microsatellite instability (MSI) at BAT-25, 0 of 16 had MSI at BAT-26 and three of 16 had MSI at BAT-40. We conclude that BAT-25, BAT-26 and BAT-40 microsatellites are insensitive to RER+ AML. Further studies are required to determine a consensus panel of sensitive microsatellites for use in AML.
Asunto(s)
Leucemia Mieloide/genética , Repeticiones de Microsatélite/genética , Enfermedad Aguda , Adulto , Anciano , Disparidad de Par Base , Línea Celular Tumoral , Reparación del ADN , Marcadores Genéticos/genética , Homocigoto , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y EspecificidadRESUMEN
We report the outcomes of reduced-intensity allogeneic stem cell transplantation using BEAM-alemtuzumab conditioning (carmustine, etoposide, cytosine arabinoside, melphalan, and alemtuzumab 10 mg/d on days -5 to -1) in 6 United Kingdom transplant centers. Sixty-five patients with lymphoproliferative diseases underwent sibling (n = 57) or matched unrelated donor (n = 8) transplantation. Sustained donor engraftment occurred in 60 (97%) of 62 patients. Of the 56 patients undergoing chimerism studies, 35 (63%) had full donor chimerism. Overall, 73% were in complete remission (CR) after transplantation. At a median follow-up of 1.4 years (range, 0.1-5.6 years), 37 remain alive and in CR. Acute graft-versus-host disease (GVHD) occurred in 11 (17%) of 64, grades I-II only. Estimated 1-year transplantation-related mortality (TRM) was 8% for patients undergoing first transplantation but was significantly worse for those who had previously undergone autologous transplantation. Six patients relapsed (estimated 2-year relapse risk, 20%). Histologic diagnosis (mantle cell lymphoma and high-grade non-Hodgkin lymphoma) and age at transplantation (> 46 years) were significantly associated with higher relapse risk and worse event-free survival. Relapse did not occur in any patient who developed acute or chronic GVHD. This study demonstrates that reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases using a BEAM-alemtuzumab preparative regimen is associated with sustained donor engraftment, a high response rate, minimal toxicity, and a low incidence of GVHD.