Faculty Bibliography

BACKGROUND CONTEXT: Pre-donation of autologous blood prior to spine fusion for adolescent idiopathic scoliosis (AIS) has been common practice. However, the effect of predonation on pre-incision hematocrit has not been studied. This study aims to determine if pre-donation of autologous blood leads to a lower pre-incision hematocrit. PURPOSE: To compare the effects of autologous blood donation on preincisional hematocrit levels. STUDY DESIGN/SETTING: Retrospective cohort study of prospective randomized trial. PATIENT SAMPLE: Patients (ages 10-21) undergoing posterior spinal fusion in a prospective, randomized controlled trial in which 125 patients were randomized to TXA, EACA, or Saline for surgery from January 2009 to January 2011. Of the 125 patients that enrolled in the study, 28 patients donated blood and 62 patients did not donate blood. 35 patients were omitted as the autologous blood donation status was not clearly documented in the medical record. OUTCOME MEASURES: Primary outcome measure was the pre-incisional hematocrit of patients immediately prior to surgery. METHODS: This is a retrospective review of data from a prospective, randomized controlled trial in which 125 patients were randomized to TXA, EACA, or Saline for surgery from January 2009 to January 2011. As part of the prospective study, all patients had a complete blood count (CBC) drawn just prior to incision. Of the 125 patients that enrolled in the study, 28 patients donated blood and 62 patients did not donate blood. 35 patients were omitted as the autologous blood donation status was not clearly documented in the medical record. Patient demographics and CBC values were compared between groups using a T-test. Statistical significance was achieved at P<0.05. RESULTS: Pre-donation patients (n528) had an average age of 15.662.2and were 75% female (21F, 7M) which was comparable to non-donation patients (n562) who had a mean age of 15.0 +/- 2.3 and were 82% female (51F, 11M) (p=0.259, p=0.425 respectively). However, pre-donation!

Recent advances in Hodgkin lymphoma research are expected to prelude a promising new treatment era for patients and their treating physicians. Scientific investigations over the last few years have provided new insights into risk stratification, and, simultaneously, a plethora of novel targeted therapies are emerging for patients with relapsed and refractory disease. These novel therapies will be tested primarily in high-risk patients because 75% of the patients are cured with conventional therapies. The challenges, as Hodgkin lymphoma therapy moves forward, will be using these biologic insights to identify the patients who may benefit earlier in treatment from these novel agents, and tailoring the therapy to the tumor biology of the patient. These dual aims are intertwined; as our therapeutic arsenal increases, these biologic determinants of risk may themselves inform the design of therapies and the choice of treatments for high-risk patients. Clin Cancer Res; 19(11); 2797-803. (c)2013 AACR.

PURPOSE: Long peptides are efficiently presented to both CD4(+) and CD8(+) T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from a human tumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations. EXPERIMENTAL DESIGN: Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination. Patients in Cohort 1 (n = 4) received 1.0 mg OLP, Cohort 2 (n = 13) received OLP in Montanide-ISA-51, and Cohort 3 (n = 11) received OLP + 1.4 mg Poly-ICLC in Montanide-ISA-51 on weeks 1, 4, 7, 10, and 13. Humoral and cellular responses were evaluated by standardized immunomonitoring techniques (ELISA, ELISPOT assay, intracellular cytokine staining, and tetramer staining). RESULTS: The vaccine was generally well tolerated with injection site reactions and fatigue that resolved. NY-ESO-1-specific antibody and CD8(+) T cells were undetectable after vaccination with OLP alone, but were found in 6 of 13 (46%) and 8 of 13 (62%) patients, respectively, after vaccination with OLP+Montanide, and in 10 of 11 (91%) and 10 of 11 (91%) patients, respectively, after vaccination with OLP+Montanide+Poly-ICLC. NY-ESO-1-specific CD4(+) T cells were detected in all patients with greater frequency and polyclonality when Montanide-ISA-51 was used for vaccination. Inclusion of Poly-ICLC as an adjuvant further accelerated the induction of NY-ESO-1-specific immune responses. CONCLUSIONS: The current study shows that NY-ESO-1 OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody, CD8(+) and CD4(+)) in nearly all vaccinated patients when given with appropriate adjuvants. Clin Cancer Res; 18(23); 6497-508. (c)2012 AACR.

CD30 expression is characteristic of the malignant Reed-Sternberg cell in Hodgkin lymphoma (HL) and several other lymphoid malignancies, such as anaplastic large-cell lymphoma (ALCL). Although unconjugated anti-CD30 antibodies have had minimal therapeutic activity in patients with HL as single agents, the CD30-directed antibody-drug conjugate (ADC) brentuximab vedotin has demonstrated activity that has resulted in its recent regulatory approval for the treatment of patients with relapsed HL and ALCL. Approximately 75% of patients with recurrent HL achieve objective responses, with the principal toxicity being peripheral neuropathy. Ongoing studies are evaluating treatment with this agent as part of first-line therapy, for patients with relapsed disease, and for patients with resistant disease and limited other options. Brentuximab vedotin demonstrates the therapeutic value of antibody-drug conjugation and serves as a model of how a novel, targeted approach can be employed to potentially further improve outcomes in settings where curative chemotherapeutic regimens are already available.

PURPOSE OF REVIEW: Although enormous progress has been made in treating non-Hodgkin's lymphoma (NHL), and some patients can be cured with combination immunochemotherapy, patients with relapsed and refractory lymphoma often succumb to their disease. Advances in our understanding of lymphoma biology and molecular pathogenesis are yielding new therapeutic targets. RECENT FINDINGS: This article reviews NHL biology and describes how our understanding of molecular pathogenesis is leading to the discovery of many therapeutic targets, including the cell signaling and cell cycle regulatory proteins, pro-apoptotic family members, the B-cell antigen receptor (BCR), and histone deacetylase. Recent preclinical and clinical data with inhibitors of phosphatidylinositol 3-kinase, AKT, mammalian target of rapamycin, histone deacetylase, bcl-2, and the Bruton's tyrosine kinase, a pivotal enzyme in the BCR pathway, are discussed. SUMMARY: Understanding these novel targets in the context of NHL biology will bring new therapies and allow us to develop new therapeutic platforms for the treatment of relapsed and refractory NHL, and will hopefully improve the clinical outcome for these patients