Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Daunorrubicina/administración & dosificación , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Inducción de Remisión , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-κB-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/genética , Aberraciones Cromosómicas , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/inducido químicamente , Adulto , Anciano , Secuencia de Bases , Ácidos Borónicos/administración & dosificación , Bortezomib , Células Clonales , Dexametasona/administración & dosificación , Progresión de la Enfermedad , Evolución Molecular , Femenino , Estudios de Seguimiento , Eliminación de Gen , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mieloma Múltiple/complicaciones , Mieloma Múltiple/genética , Mutación , FN-kappa B/genética , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple/genética , Pirazinas/administración & dosificación , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína de Retinoblastoma/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
A 33-year-old man with an atypical course of hypereosinophilic syndrome including malignant hypercalcemia, osteolytic lesions and evolution into severe myelofibrosis was treated by allogeneic bone marrow transplantation after conditioning with cytoxan and total body irradiation. As the transplant was sex-mismatched, chimerism was studied by means of cytogenetic analysis and Y chromosomal DNA amplification by PCR assay. Long-term complete remission has been assessed by normalization of blood cell counts, magnetic resonance imaging and karyotypic analysis. A relapse was observed 40 months after transplantation. The patient remains alive 44 months post-BMT. This case report is compared with those reported in the literature.
Asunto(s)
Trasplante de Médula Ósea , Síndrome Hipereosinofílico/terapia , Mielofibrosis Primaria/terapia , Adulto , Humanos , Síndrome Hipereosinofílico/fisiopatología , Masculino , Trasplante HomólogoRESUMEN
We report on two cases of central nervous system (CNS) relapse after high-dose chemotherapy and autologous stem cell transplantation. A 55-year-old man received two courses of vincristin, doxorubicin and dexamethasone (VAD) as an induction treatment for stage IIIB IgG kappa multiple myeloma. Bone marrow stem cell collection was performed after a high-dose melphalan (HDM) course (140 mg/m2). Autologous bone marrow transplantation (ABMT) was performed with this cryo-preserved unpurged bone marrow sample after a second HDM course. Three months after ABMT, the patient presented with signs of central nervous involvement with plasma cells and monoclonal IgG kappa in the cerebral fluid. The patient died despite systemic and intrathecal chemotherapy. A 50-year-old man was initially treated with 3 courses of VAD for a stage IIIA IgD lambda multiple myeloma. Blood stem cell were collected after a course of high-dose etoposide and cyclophosphamide. ABMT was performed after total body irradiation (TBI) and HDM. Three months later, he presented with right leg palsy and a lumbar puncture showed numerous plasma cells and the presence of the IgG lambda. The patient died of neurological complications three months later. Extramedullary occurred prior to medullary relapse in the two cases, suggesting the presence of an extramedullary clone of plasma cells with a high degree of chemo-resistance. Although high-dose chemotherapy appears promising, this therapeutic approach could allow the occurrence of presently unobserved complications. Wether CNS prophylaxis is indicated in this context, as recommended in leukemia, remains an open question.