RESUMO
UNLABELLED: Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13-5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34(+) and CD8(+) cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34(+) and CD8(+) leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical. TRIALS: gov with the number NC01423747.
Assuntos
Linhagem da Célula , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Quimeras de Transplante , Adolescente , Biomarcadores , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Lactente , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Recidiva , Medição de Risco , Fatores de Risco , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
The overall costs of pediatric stem cell transplantation (SCT), including donor search and costs during the first year post-SCT, were calculated in a cohort of 141 consecutive children undergoing SCT in a single institution. Costs were correlated with patient and transplantation characteristics and with a risk score for transplantation-related mortality. Cost-effectiveness was calculated based on the overall cost per surviving patient. Life-years gained were extrapolated from overall survival, and the costs per expected life-year gained were calculated. The overall median cost was 136,382 (175,815$), with a wide range, of 26,897 (34,679$) to 601,348 (775,343$). Increased costs were significantly associated with age, use of donors other than matched siblings, and advanced disease. There was a strong correlation of costs with a simple transplantation-related mortality risk score; median total costs were 89,550 (115,463$) for a score of 0, 127,349 (164,179$) for a score of 1, 156,578 (201,861$) for a score of 2, and 274,915 (354,499$) for a score of 3 (P < .001). Cost-effectiveness decreased with increasing transplantation-related mortality risk score; costs per survivor increased from 93,209 (120,200$) for a score of 0 to a maximum of 1,216,348 (1,568,579$) for a score of 3. Costs associated with pediatric SCT vary substantially; however, the combination of variables such as age, disease, and donor type is predictive of costs and cost-effectiveness. Costs per life-year gained are within the broadly accepted range in life-threatening hemato-oncologic diseases, even in the most cost-intensive patient cohort.