RESUMO
Thalassemia-free survival after allogeneic stem cell transplantation (SCT) is about 80-90% with either matched-related or -unrelated donors. We explored the use of a mismatched-related ('haplo- ') donor. All patients received two courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine (Flu) and dexamethasone (Dxm). After two courses of PTIS, a conditioning regimen of rabbit antithymocyte globulin, Flu and IV busulfan (Bu) was given followed by T-cell-replete peripheral blood progenitor cells. GvHD prophylaxis consisted of cyclophosphamide (Cy) on days SCT +3 and +4 (post-Cy), and on day SCT +5 tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Thirty-one patients underwent haplo-SCT. Their median age was 10 years (range, 2-20 years). Twenty-nine patients engrafted with 100% donor chimerism. Two patients suffered primary graft failure. Median time to neutrophil engraftment was 14 days (range, 11-18 days). Five patients developed mild to moderate, reversible veno-occlusive disease, while nine patients developed acute GvHD grade II. Only five patients developed limited-chronic GvHD. Projected overall and event-free survival rates at 2 years are 95% and 94%, respectively. The median follow up time is 12 months (range, 7-33 months).
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante Haploidêntico/métodos , Talassemia beta/terapia , Adolescente , Remoção de Componentes Sanguíneos , Criança , Pré-Escolar , Intervalo Livre de Doença , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Hemoglobina E , Homozigoto , Humanos , Imunossupressores/uso terapêutico , Lactente , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
INTRODUCTION: This is the first pilot study to screen multiple common genetic aberrations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). METHODS: Thirty-two children with BCP-ALL were investigated for chromosomal rearrangements using interphase fluorescence in situ hybridization (FISH). Eight common translocations and rearrangements, including ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, ETV6, TCF3, MLL, IGH@, and PAX5, were tested for using dual-color DNA probes. RESULTS: ETV6-RUNX1 was the most frequent translocation detected in 11 children (34.4%). Two patients with BCR-ABL1 (6.3%) and one with TCF3-PBX1 (3.1%) translocations were also observed. Using break-apart probes, 11 children (34.4%) had a positive FISH result for ETV6, two patients for IGH@ (6.3%), one patient for MLL (3.1%), and one patient for PAX5 rearrangements (3.1%). All patients with the ETV6-RUNX1 fusion were also identified by split signals for ETV6. Other abnormalities, including extra copies and deletion of genes, were observed within the range of 3.1-34.4%. Cytogenetics analysis showed a single case each of BCR-ABL1 fusion, MLL, and IGH@ rearrangements (3.1% each). ETV6-RUNX1 fusion and ETV6 split-apart rearrangements were not visible by cytogenetics. Likewise, one each of cases with TCF3-PBX1 fusion and with PAX5 split signal seen by FISH was not visible by cytogenetics. CONCLUSION: By using 8 FISH probes in conjunction cytogenetics for the detection of common aberrations, interphase FISH enhanced the detection of chromosomal rearrangements in children with BCP-ALL.
Assuntos
Linfócitos B/patologia , Hibridização in Situ Fluorescente/estatística & dados numéricos , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Translocação Genética , Doença Aguda , Adolescente , Linfócitos B/metabolismo , Criança , Pré-Escolar , Feminino , Testes Genéticos , Humanos , Lactente , Interfase/genética , Cariotipagem , Masculino , Proteínas de Fusão Oncogênica/metabolismo , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologiaRESUMO
A 7-month-old Myanmar boy was admitted with a 3-day history of fever. He was markedly pale and his temperature was 38·2°C. Peripheral blood smear demonstrated Plasmodium vivax infection with spherocytosis and auto-agglutination of red blood cells. Haematocrit was 16% and reticulocyte count 14·9%. Direct and indirect antiglobulin tests were positive. Antibody analysis was positive for auto-antigen I. P. vivax malaria with auto-immune haemolytic anaemia (AIHA) was diagnosed. He was treated with chloroquine and primaquine for the P. vivax infection, and oral prednisolone for the AIHA. Because of the clinical symptoms of anaemia and mild dyspnoea, blood with the least incompatible red blood cells was transfused. The clinical symptoms and signs improved. At follow-up 3 and 7 weeks after treatment, his haematocrit, reticulocyte count and peripheral blood smear results were within normal limits. Prednisolone was then tapered and stopped. The patient has since been well with no detectable recurrence of AIHA.
