Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/administración & dosificación , Trasplante de Células Madre de Sangre del Cordón Umbilical , Acondicionamiento Pretrasplante , Donante no Emparentado , Aloinjertos , Anemia Aplásica/mortalidad , Suero Antilinfocítico/efectos adversos , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/µl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.
Asunto(s)
Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Dominios y Motivos de Interacción de Proteínas/genética , Proteínas Tirosina Quinasas/genética , Adolescente , Biomarcadores de Tumor , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Humanos , Factor de Transcripción Ikaros/genética , Lactante , Janus Quinasa 2/genética , Japón , Masculino , Mutación , Proteínas de Fusión Oncogénica/química , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del TratamientoAsunto(s)
Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto , Niño , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Femenino , Humanos , Incidencia , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Factores de Riesgo , Donantes de Tejidos , Trasplante Homólogo , Adulto JovenRESUMEN
The outcome of 55 children with severe aplastic anemia (SAA) who received a second hematopoietic stem cell transplantation (HSCT) was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival (OS) and failure-free survival (FFS) after the second transplantation were 82.9% (95% confidence interval (CI), 69.7-90.8)) and 81.2% (95% CI, 67.8-89.4), respectively. FFS was significantly better when the interval between the first and second transplantation was >60 days (88.9%; 95% CI, 73.0-95.7) than when it was ⩽60 days (61.4%; 95% CI, 33.3-80.5; P=0.026). All 12 patients who were conditioned with regimens containing fludarabine and melphalan were alive with hematopoietic recovery. These findings justify the recommendation of a second HSCT for children with SAA who have experienced graft failure after first HSCT.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Anemia Aplásica/mortalidad , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Análisis de SupervivenciaRESUMEN
Primary graft failure (pGF) is associated with considerable morbidity and mortality. Salvage hematopoietic SCT (HSCT) can rescue pGF patients; however, the optimal preconditioning regimen and stem cell source are yet to be determined, particularly in children. In this study, we retrospectively analyzed 102 pediatric patients who received salvage allogeneic HSCT for pGF. Salvage HSCT from matched or one-Ag-mismatched related donors (rMM01) provided superior OS compared with that from two- or three-Ags-mismatched related donors (rMM23) or cord blood transplantation (CBT). CBT showed a trend toward a slightly lower engraftment rate and late engraftment achievement compared with rMM23; however, the OS rate was similar between the two groups (47.6±7.7% for rMM23 and 45.7±8.6% for CBT, at 1 year after salvage HSCT). Multivariate analysis showed that preconditioning regimens with fludarabine or irradiation were associated with a higher engraftment rate and those with alkylating agents were associated with better OS. In conclusion, our results showed that rMM01 was the most suitable donor for salvage HSCT for pediatric pGF, and that CBT was an equally important option compared with rMM23 for patients without rMM01.
Asunto(s)
Rechazo de Injerto/cirugía , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Niño , Preescolar , Supervivencia de Injerto , Humanos , Lactante , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo , Resultado del TratamientoAsunto(s)
Vacunas contra el Cáncer/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Proteínas WT1/química , Proteínas WT1/uso terapéutico , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Leucemia/genética , Leucemia/inmunología , Masculino , Péptidos/química , Péptidos/inmunología , ARN Mensajero/análisis , ARN Mensajero/genética , Recurrencia , Riesgo , Linfocitos T Citotóxicos/inmunología , Trasplante Homólogo , Proteínas WT1/genética , Proteínas WT1/inmunologíaRESUMEN
In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.1+/-5.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%). Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.
