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We present an approach for evaluating the efficacy of combination antitumor agent schedules that accounts for order and timing of drug administration. Our model-based approach compares in vivo tumor volume data over a time course and offers a quantitative definition for additivity of drug effects, relative to which synergism and antagonism are interpreted. We begin by fitting data from individual mice receiving at most one drug to a differential equation tumor growth/drug effect model and combine individual parameter estimates to obtain population statistics. Using two null hypotheses: (i) combination therapy is consistent with additivity or (ii) combination therapy is equivalent to treating with the more effective single agent alone, we compute predicted tumor growth trajectories and their distribution for combination treated animals. We illustrate this approach by comparing entire observed and expected tumor volume trajectories for a data set in which HER-2/neu-overexpressing MCF-7 human breast cancer xenografts are treated with a humanized, anti-HER-2 monoclonal antibody (rhuMAb HER-2), doxorubicin, or one of five proposed combination therapy schedules.A ssessing the efficacy of a combination of antitumor agents by analyzing in vivo tumor growth is an increasingly popular experimental design. However, analyses of tumor growth curves and of drug interactions are both complex statistical problems. Many methods for assessing growth address only a univariate summary, such as doubling time or tumor volume at an arbitrary endpoint, and either lack power or inflate the type I error rate (1). Multivariate methods that use the entire nonlinear growth curve are preferred (1, 2), but most published methods have been limited to linear growth models that may not be appropriate for long time courses or multiple-drug administration. No method of which we are aware has incorporated differences in drug administration time and/or order of drug administration in a statistical analysis comparing treatment schedules.Another stumbling block in evaluating combination therapy is clearly defining additivity or summation of effect (also referred to as ''independence'') (3). Antagonism or synergism is generally interpreted as an outcome that falls short of or exceeds, respectively, the effect expected from a purely additive interaction of individual drugs. There is, however, much debate as to how these quantities are to be calculated (4), and their definitions are often context and model dependent, particularly for nonlinear doseeffect relationships. Some definitions focus on addition of effects, whereas others consider the combinations of doses necessary to reach a preset effect. These definitions are not equivalent except, perhaps, when the system is linear. Consequently, there is no consensus on a quantitative definition of synergism and antagonism. Finally, most classical methods for assessing drug additivity (4-7) are designed only for a univariate measure of drug effectiveness and require experimental data at multiple doses to de...

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive malignancy that usually presents with diffuse cutaneous lesions. While a favorable response to therapy occurs in a majority of cases, a sustained long-term response is uncommon. Most patients subsequently relapse within a year. In the following report, we present the case of a 41-year-old woman who has not displayed many of the clinical features traditionally associated with BPDCN. The patient received sporadic chemotherapy treatment over the course of 2 years, before undergoing an allogeneic stem cell transplant. Although she ultimately relapsed following her transplant, her disease has repeatedly returned into remission after donor lymphocyte infusion (DLI). Currently, the patient is in remission following her fourth DLI. We believe that allogeneic transplantation should be considered as front-line therapy for the treatment of this rare malignancy.

4589 Background: Burkitt lymphoma is a highly aggressive and rapidly proliferating hematologic malignancy. Various chemotherapy regimens (HyperCVAD, CODOX-M/IVAC, REPOCH) have been shown to improve overall survival rate. However, in instances of relapsed or refractory disease, there is no clear-cut standard of care. Hematopoietic stem cell transplantation (HCT) has shown benefit in these patients. Here, we report our institutional experience using HCT for relapsed/refractory Burkitt lymphoma. Methods: Between February 1994 and January 2010, 13 patients (10 males, 3 females) with refractory or relapsed Burkitt lymphoma were retrospectively evaluated. The patients in question were administered a particular conditioning regimen followed by stem cell transplantation (11 autologous, 2 allogeneic). The average age at transplant was 41.8± 3.4 years (range 24 to 67). Stem cell source was from peripheral blood in all transplants including allogeneic (2 HLA-identical sibling transplants). The conditioning regimens for HCT consisted of the following: TBI/Rituximab/Cytoxan/VP16, TBI/Cytoxan/VP16, BEAM, Cranial Spinal boost/TBI/Cytoxan/VP16 or Cranial boost/TBI/Cytoxan. Results: On average, patients received transplant 299 ± 36 days after initial diagnosis (range 153 to 582). All patients achieved engraftment. For the 5/13 deceased patients (38%), cause of death was attributed to relapsed/refractory disease (n=2) and treatment related causes (n=3). Using the Kaplan-Meier method, the average survival time after transplant was computed at 27.7 ± 5.3 months and 75% were alive 2-years after transplant. Likely due in part to the small sample size, no covariates (age, gender, conditioning regimen, HIV status, presence of B symptoms, and CNS or bone marrow involvement) were found to be predictive of survival rates. Conclusion: Patients with Burkitt lymphoma, known for its rapid growth, can achieve long-term complete remission (CR) with intense, combination chemotherapy. Despite successful long-term remission rates, a substantial portion of patients die from uncontrolled disease. At the first sign of refractory or relapsed disease, resources should be mobilized to proceed with HCT. Our study, though limited in size, provides further compelling evidence that long-term CR, and potentially cure, may be achieved using HCT as a treatment modality. Disclosures: No relevant conflicts of interest to declare.

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staff, leadership. 4. Rejuvenation of shared governance at the unit level. Results: To determine the influence of the ANM role, a staff engagement survey was re-administered and compared to the 2010 results. The results showed a dramatic increase in staff engagement and satisfaction, as evidenced in the attached table. In addition, since the ANM role was established, nurse certification has increased by 120% and nurses pursuing higher education has increased 700%, supporting the premise that the ANM role had a positive influence in professional nursing development. Discussion: The ANM role had a positive influence on staff engagement, satisfaction, and professional growth. Effective motivational strategies combined with a functional management structure cultivates an environment where the highest level of quality care can be delivered.