RESUMO
T-lineage ALL is an aggressive disease that needs to be treated with intensive treatment schedules. A late relapse rarely occurs and a clear choice for second-line treatment is on debate. We report on a young adult with a very late isolated extramedullary relapse of PICALM-MLLT10 positive T-ALL, successfully treated with a chemotherapy-based and radiotherapy-based pediatric protocol. We demonstrate that relapse can occur in T-ALL although a SR-MRD behavior treated with a high-risk protocol; specific molecular diagnostic aberrations, as PICALM-MLLT10, are still conserved at very late relapse; a second-line treatment based on pediatric protocol can be effective.
Assuntos
Quimiorradioterapia/métodos , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Antineoplásicos/uso terapêutico , Feminino , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Radioterapia/métodosRESUMO
The timing and developmental sequence of events for BCR-ABL1(+) acute lymphoblastic leukemia (ALL), usually associated with IKAROS (IKZF1) deletions, are unknown. We assessed the status of BCR-ABL1 and IKZF1 genes in 2 pairs of monozygotic twins, one pair concordant, the other discordant for Philadelphia chromosome positive (Ph(+)) ALL. The twin pair concordant for ALL shared identical BCR-ABL1 genomic sequence indicative of monoclonal, in utero origin. One twin had IKZF1 deletion and died after transplantation. The other twin had hyperdiploidy, no IKZF1 deletion, and is still in remission 8 years after transplantation. In the twin pair discordant for ALL, neonatal blood spots from both twins harbored the same clonotypic BCR-ABL1 sequence. Low level BCR-ABL1(+) cells were present in the healthy co-twin but lacked the IKZF1 deletion present in the other twin's leukemic cells. The twin with ALL relapsed and died after transplantation. The co-twin remains healthy and leukemia free. These data show that in childhood Ph(+) ALL, BCR-ABL1 gene fusion can be a prenatal and possibly initiating genetic event. In the absence of additional, secondary changes, the leukemic clone remains clinically silent. IKZF1 is a secondary and probable postnatal mutation in these cases, and as a recurrent but alternative copy number change is associated with poor prognosis.
Assuntos
Proteínas de Fusão bcr-abl/genética , Fator de Transcrição Ikaros/genética , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética/genética , Gêmeos Monozigóticos/genética , Criança , Pré-Escolar , Pontos de Quebra do Cromossomo , Evolução Fatal , Feminino , Deleção de Genes , Dosagem de Genes/genética , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , PrognósticoRESUMO
We report the case of a child presenting with concurrent thoracic ganglioneuroblastoma and acute myeloid leukemia. The peculiarity was the close relation between the two tumors with the latter infiltrating the former one. Histological and genomic studies indicate the different clonal origins of the malignancies in the patient, and we hypothesized that GNB and AML developed independently. Our observation suggests that in patients with more than one tumor, though discovered at different times, one neoplasm is not always secondary.
Assuntos
Ganglioneuroblastoma/patologia , Leucemia Mieloide Aguda/patologia , Neoplasias do Mediastino/patologia , Neoplasias Primárias Múltiplas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Ganglioneuroblastoma/genética , Ganglioneuroblastoma/fisiopatologia , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/fisiopatologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/fisiopatologiaRESUMO
Natural killer (NK) cell lymphomas are rare in the USA and Europe but more common in Asia and Central America although very rare among children. We report a case of Epstein-Barr virus-positive NK lymphoma/leukemia, that showed peculiar features represented by a very long clinical course with a significant interval between the first clinical signs and the diagnosis, detection of neoplastic cells in the peripheral blood but not in the bone marrow, and good response to treatment and clinical outcome.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Células Matadoras Naturais/patologia , Leucemia/diagnóstico , Linfoma/diagnóstico , Antineoplásicos Fitogênicos/uso terapêutico , Medula Óssea/imunologia , Medula Óssea/patologia , Medula Óssea/virologia , Pré-Escolar , DNA Viral/análise , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Humanos , Imunofenotipagem , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Leucemia/tratamento farmacológico , Leucemia/virologia , Linfoma/tratamento farmacológico , Linfoma/virologia , Resultado do Tratamento , Vimblastina/uso terapêuticoAssuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Ribavirina/administração & dosagem , Pré-Escolar , Quimioterapia Combinada , Feminino , Hepatite C Crônica/etiologia , Humanos , Interferon alfa-2 , Proteínas RecombinantesRESUMO
Detection of Philadelphia chromosome (Ph) in childhood T-lineage acute lymphoproliferative disorders is a rare event. Additional cytogenetic abnormalities are particularly uncommon in ALL. We here report two cases with T lineage acute lymphoproliferative disorders (T-ALL and T-NHL) presenting with both cytogenetic alterations and BCR-ABL fusion transcripts, associated with an aggressive presentation and a poor outcome. We point out firstly on the cytogenetic aberrations, supporting the hypothesis of multi-lineage involvement of ALL expressing Ph chromosome; secondly, on the persistence of T-cell leukemic clone detected by minimal residual disease (MRD) analysis, despite of the early disappearance of BCR-ABL fusion transcript.
