RESUMEN
BACKGROUND: Reduced intensity conditioning (RIC) regimens decrease the risk for nonrelapse mortality (NRM) in adult patients undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies but increase the risk for relapse. The aim of this study was to compare the outcomes of fludarabine-total body irradiation (TBI) with fludarabine among patients with hematologic diseases. PATIENTS AND METHODS: This retrospective study of 137 patients with different hematologic malignancies compared the outcomes of 63 patients who received a conventional RIC regimen with 2 days of IV busulfan (3.2 mg/kg/d × 2 days) and fludarabine with 74 patients who received the same regimen plus 400 cGy of fludarabine and busulfan (FB)-TBI divided in 2 doses over 1 day (200 cGy BID). Median follow-up was 4.62 years. RESULTS: The donors were either HLA-matched siblings (36%) or HLA-matched unrelated donors (64%). The FB-TBI showed trends toward improvement in progression-free survival (PFS) and overall survival (OS) over FB (5-year PFS rates 50% vs 34%, P = .06, and 5-year OS rate 53% vs 39%, P = .13). Acute graft-vs-host disease (aGVHD), relapse, and NRM were similar between the 2 groups. The 5-year cumulative incidence of chronic GVHD (cGVHD) was lower in the FB-TBI group compared with the FB group (29% vs 52%, P = .003). Multivariable analysis revealed that grade III-IV aGVHD was the only independent risk factor for worse OS (P = .001) in both groups. A high disease risk index was possibly associated with inferior OS (P = .07) in both groups. CONCLUSIONS: The FB-TBI is a safe and effective intensified RIC regimen for adult patients with hematologic malignancies. It predicted a lower risk for cGVHD and showed possibly improved PFS and OS compared with FB.
Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Busulfano , Estudios Retrospectivos , Irradiación Corporal Total , Recurrencia Local de Neoplasia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Vidarabina , Enfermedad Injerto contra Huésped/etiología , Acondicionamiento PretrasplanteRESUMEN
PURPOSE: To accurately hypothesize the optimal frequency of psychosocial distress screening in patients undergoing radiation therapy using exploratory modeling of prospective data. MATERIALS AND METHODS: Between October 2010 and May 2011, 71 RT patients underwent daily screening with the Distress Thermometer. Prevalences of Distress Thermometer scores ≥ 4 were recorded. Optimal screening frequency was evaluated by planned post hoc comparison of prevalence rates and required screening events estimated by numerical modeling, consisting of data point omission to mimic weekly, every-other-week, monthly, and one-time screening intervals. Dependence on clinical variables and chronologic trends were assessed as secondary end points. RESULTS: A total of 2,028 daily screening events identified that 37% of patients reported distress at least once during the course of treatment. Weekly, every-other-week, monthly, and one-time screening models estimated distress prevalences of 32%, 31%, 23%, and 17%, respectively, but required only 21%, 12%, 7%, and 4% of the assessments required for daily screening. No clinical parameter significantly predicted distress in univariable analysis, but "alone" living situation trended toward significance (P = .06). Physician-reported grade 3 toxicity predicted distress with 98% specificity, but only 19% sensitivity. CONCLUSION: Thirty-seven percent of radiation oncology patients reported distress at least once during treatment. Screening at every-other-week intervals optimized efficiency and frequency, identifying nearly 90% of distressed patients with 12% of the screening events compared with daily screening.
Asunto(s)
Modelos Psicológicos , Neoplasias/psicología , Neoplasias/radioterapia , Oncología por Radiación , Estrés Psicológico/diagnóstico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia/efectos adversos , Factores de TiempoRESUMEN
Networks of transcription factors (TFs) are thought to determine and maintain the identity of cells. Here we systematically repressed each of 100 TFs with shRNA and carried out global gene expression profiling in mouse embryonic stem (ES) cells. Unexpectedly, only the repression of a handful of TFs significantly affected transcriptomes, which changed in two directions/trajectories: one trajectory by the repression of either Pou5f1 or Sox2; the other trajectory by the repression of either Esrrb, Sall4, Nanog, or Tcfap4. The data suggest that the trajectories of gene expression change are already preconfigured by the gene regulatory network and roughly correspond to extraembryonic and embryonic fates of cell differentiation, respectively. These data also indicate the robustness of the pluripotency gene network, as the transient repression of most TFs did not alter the transcriptomes.