Objective: To define clinical, radiographic, and blood-based biomarker features to be incorporated into a classification model of progression of intracranial hemorrhage (PICH), and to provide a pilot assessment of those models. Methods: Patients with hemorrhage on admission head computed tomography were identified from a prospectively enrolled cohort of subjects with traumatic brain injury. Initial and follow-up images were interpreted both by 2 independent readers, and disagreements adjudicated. Admission plasma samples were analyzed and principal components (PCs) composed of the immune proteins (IPs) significantly associated with the outcome of interest were selected for further evaluation. A series of logistic regression models were constructed based on (1) clinical variables (CV) and ( 2) clinical variables + immune proteins (CV+IP). Error rates of these models for correct classification of PICH were estimated; significance was set at P < .05. Results: We identified 106 patients, 36% had PICH. Dichotomized admission Glasgow Coma Scale (P = .004), Marshall score (P = .004), and 3 PCs were significantly associated with PICH. For the CV only model, sensitivity was 1.0 and specificity was 0.29 (95% CI, 0.07-0.67). The CV+IP model performed significantly better, with a sensitivity of 0.93 (95% CI, 0.64-0.99) and a specificity of 1.0 (P = .008). Adjustments to refine the definition of PICH and better define radiographic predictors of PICH did not significantly improve the models' performance. Conclusions: In this pilot investigation, we observed that composites of IPs may improve PICH classification models when combined with CVs. However, overall model performance must be further optimized; results will inform feature inclusion included in follow-up models.
Patients with post-allogeneic HSCT disease relapse can be treated with salvage chemotherapy but are also candidates for immune suppression withdrawal and/or donor lymphocyte infusion (DLI). A total of 237 adult patients experienced relapse of disease post-allogeneic transplant at our institution between 1995 and 2010. A retrospective institutional analysis was performed on the 52 patients who received DLI in that timeframe. The DLI product infusion doses ranged from 0.07 to 4.0 x 10 8 CD3+ cells. CML patients had the most favorable DLI response rates with 78% (n 5 7) in remission at 3 years. Patients with relapsed AML/ MDS and lymphoid malignancies fared worse with 36% and 21% OS at 3 years respectively. OS was superior in patients in CR prior to DLI (45%) compared to those with active disease (5%) and for patients under the age of 50 (32% vs 21%). Three year OS was observed of 5% for patients who relapsed prior to day +100, 29% for relapse between day +100 and 1 year, and 59% for relapse after 1 year. Patients who developed GvHD prior to relapse had a 3 year OS of 35% vs 9% in patients without GvHD. Patients with post-DLI GvHD had a 39% OS vs 11% for patients without GvHD after DLI. No difference in post-DLI survival was noted with regards to pre-transplant disease status, cell dose or transplant conditioning. CML patients respond well to DLI however in the TKI era, transplants for these patients are reserved for patients with TKI-resistant disease. In other patients, immune suppression withdrawal and DLI have limited efficacy for those who do not achieve CR post-relapse or who relapse within 3 months of transplant. These patients are in need of alternative treatment strategies.
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