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Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti–T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days −3, −2, −1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Purpose: Inpatient academic medical center care historically has been delivered by faculty physicians in conjunction with physicians in training (house officers [HOs]). Alternative staffing models have emerged secondary to American Counsel for Graduate Medical Education work-hour restrictions. The purpose of this study was to assess the quality of acute myelogenous leukemia (AML) care provided by a physician assistant (PA) service compared with a traditional model. Patients and Methods: Data were retrospectively collected on patients admitted with AML for reinduction chemotherapy from 2008 to 2012. Primary outcome measures were inpatient mortality and length of stay (LOS). Secondary measures included readmissions, intensive care unit (ICU) transfers, consults requested, and radiologic studies ordered. Results: Ninety-five patients with AML were reviewed. Fortyseven patients (49.5%) were admitted to the HO service, and 48 patients (50.5%) were admitted to the PA service. Demographic data were similar between services. LOS was significantly different between the services, with a mean of 36.8 days with the HO model compared with 30.9 days with the PA service (P .03). The 14-day readmission rate also differed significantly; it was 10.6% (five of 47 patients) and zero for the HO and PA models, respectively (P .03). The mean number of consults with the HO model was 2.11 (range, zero to five) versus 1.47 (range, zero to four) with the PA service (P .03). Mortality and ICU transfers were not significantly different. Conclusion: The data demonstrate equivalent mortality and ICU transfers, with a decrease in LOS, readmission rates, and consults for patients cared for in the PA service. This suggests that the PA service is associated with increased operational efficiency and decreased health service use without compromising health care outcomes.

Purpose HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell transplantation (HSCT) is associated with increased graft-versus-host disease (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory properties potentially beneficial for control of GVHD in T-cell-replete HLA-mismatched transplantation. Patients and Methods We conducted a prospective phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib, administered once per day on days +1, +4, and +7 after peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients: 40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up. Results The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI, 16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively. Two-year progression-free survival and overall survival were 51% (95% CI, 36% to 64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our institution. Immune recovery, including CD8+ T-cell and natural killer cell reconstitution, was enhanced with bortezomib. Conclusion A novel short-course, bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC HSCT, can enhance early immune reconstitution, and appears to be suitable for prospective randomized evaluation.

PURPOSE: The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non–Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a large cohort of patients who developed MDS after ABMT for NHL. PATIENTS AND METHODS: Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies. MDS was strictly defined, using the French-American-British classification system, as requiring bone marrow dysplasia in at least two cell lines, with associated unexplained persistent cytopenias. RESULTS: Forty-one patients developed MDS at a median of 47 months after ABMT. The incidence of MDS was 7.4%, and actuarial incidence at 10 years is 19.8%, without evidence of a plateau. Patients who developed MDS received significantly fewer numbers of cells reinfused per kilogram at ABMT (P = .0003). Karyotypes were performed on bone marrow samples of 33 patients, and 29 patients had either del(7) or complex abnormalities. The median survival from diagnosis of MDS was 9.4 months. The International Prognostic Scoring System for MDS failed to predict outcome in these patients. Thirteen patients underwent allogeneic BMT as treatment for MDS, and all have died of BMT-related complications (11 patients) or relapse (two patients), with a median survival of only 1.8 months. CONCLUSION: Long-term follow-up demonstrates a high incidence of MDS after ABMT for NHL. The prognosis for these patients is uniformly poor, and novel treatment strategies are needed for this fatal disorder.

Patients with acute myeloid leukemia (AML) in first remission are risk stratified using an integrated profile that incorporates response assessment, cytogenetics, and molecular genetic data. The purpose is to identify which patients may benefit from allogeneic transplantation versus chemotherapy alone as postremission therapy (PRT). Patients with high-risk profiles are often referred for transplantation, whereas those with a favorable-risk profile usually receive chemotherapy alone. An increasing number of recurring mutations is being identified in patients with AML, which helps to further refine the risk profile for these patients. This additional genetic information is especially helpful in managing the large number of patients with an intermediate cytogenetic–risk profile; this population of patients is increasingly recognized to be heterogeneous at a genetic level. Adding to the importance of better understanding the risk profile of these patients is a recent decision analysis that demonstrated an improved outcome with allogeneic transplantation for patients with intermediate-risk profiles compared with those receiving conventional chemotherapy. Given the toxicities and benefits of allogeneic transplantation, it is imperative that patients who would not benefit from transplantation are identified and treated with chemotherapy, sparing them the risks of transplantation. In contrast, those patients with a higher risk of relapse may benefit from allogeneic transplantation in first complete remission (CR1). The article by Rollig et al that accompanies this editorial demonstrates an improved relapse-free survival in patients harboring the NPM1 mutation who received transplantation from a sibling donor compared with those who received chemotherapy alone. The trial used a donor versus no donor random assignment and retrospectively looked at the impact of NPM1 mutation on both relapse and overall survival. NPM1 mutations, which are present in a large percentage of patients with AML who have a normal karyotype, are considered a favorable prognostic marker. Mutations of the NPM1 gene in exon 12 result in aberrant cytoplasmic expression of the abnormal nucleophosmin proteins. NPM1 mutation is associated with an increased frequency of FLT-3 expression and CD34 phenotype and also defines a distinctive gene profile. In a subset of 401 patients with AML with a normal karyotype, NPM1 mutations were identified in nearly 53% of patients. In more than 40% of patients with NPM1 mutations, there was also a mutation of FLT3. The presence of the NPM1 mutation alone was associated with improved outcome, with remission rates of 70% versus 55% for those without the NPM1 mutations. A trend toward improved overall survival and progression-free survival has been noted. These results are similar to the high remission rates seen in patients with core binding factor (CBF) mutations. Given these findings, the European LeukemiaNet grouped the patients with mutated NPM1 without FLT3/internal tandem duplication and normal karyotype into the favorable prognostic group. In a validation of the prognostic recommendations from the European LeukemiaNet, patients with CBF mutations had an improved median overall survival of 135 months compared with 23 months for patients with the NPM1 mutation/FLT3-negative genotype, whereas patients with the NPM1/FLT3-negative profile still had a near doubling of overall survival compared with a median overall survival of 13 months for patients with an intermediate-risk 1 or 2 profile. Although this difference justified the continued designation as favorable, the most appropriate PRT remains debatable. Should patients with a normal karyotype and NPM1 mutations be referred for allogeneic transplantation in CR1? The authors of the European LeukemiaNet prognostic validation suggest that transplantation should be considered as an option for these patients. As with patients with CBF mutations, excellent outcomes are seen after transplantation in this group. In a study of 101 patients with the NPM1/ FLT3-negative genotype undergoing transplantation beyond CR1, 2-year overall survival was 81%. There is also a suggestion that the NPM1 phenotype may elicit an enhanced graft-versus-leukemia effect. There are no randomized trials to address the issue of the most effective PRT for patients with NPM1 mutations. A prospective randomized controlled trial is considered the gold standard for trial design to eliminate selection bias. The most obvious potential biases in trials involving transplantation relate to referral of only the young and fit for transplantation, whereas those who are older or with comorbidities and those less likely to withstand the rigors of transplantation may be referred for chemotherapy alone. There are practical concerns as well. Because only 30% of eligible patients will have a sibling donor available to make transplantation an option, the sample size to answer a question involving allogeneic transplantation in a clinical trial becomes too JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 5 FEBRUARY 1

183 Background: Hematopoietic stem cell transplantation (HCT) is a complex process in which patient education is increasingly recognized as a critical element to enhance patient preparedness and survivorship. Diet-related education to prevent infectious complications is an essential part of HCT care. Current teaching methods include one-on-one clinician/patient discussion supported with printed materials. Video based teaching may strengthen the learning process of patients and their caregivers. The audio and interactive components may be particularly useful in older patients as sensory ability declines with age. Methods: Focus group methodology was utilized. Four groups of patients, nurses, physicians, pharmacists and dietitians were asked semi-structured questions to allow for collection of systematic data. Multiple rounds of content analysis were used to eliminate duplicates and identify common themes. An interactive video based on items identified and institutional protocols was developed. After refinement of both content and usability, the video was presented to 10 patients and their caregivers admitted to the hospital for HCT. They were instructed on its use and given unlimited time to view it. A survey was conducted by a member of the HCT team to collect feedback regarding length and content of the program. Results: All patients felt the program was a helpful supplement to the written materials. They also felt that the content was consistent and the program was easy to use. Two patients said the video was long, though commented positively on how comprehensive it was. One patient preferred printed materials to have during food preparation. All patients requested that the video be available to view after discharge. Conclusions: Feedback from a multidisciplinary team was instrumental in the development of an interactive tool reviewing post-HCT nutrition guidelines. Feedback from an initial cohort of patients has been positive in regards to usability and knowledge gained. This video will enhance patient and caregiver education and allow them the ability to take an active role in their HCT care. Next steps include a more formal evaluation of clinical outcomes related to this method of learning.

272 Background: Readmission within 30 days of discharge has been perceived by the Centers for Medicare and Medicaid Services to be an indicator of poor healthcare quality, however it is unclear how accurately this applies to oncology patients. Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of readmission, but the incidence following umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence, reasons, and risk factors for readmission following UCBT. Methods: A retrospective review of patients receiving an UCBT at Dana-Farber/Brigham and Women’s Hospital between January 1, 2004 and December 31, 2013 was performed. The 30-day and the day +100, a traditional assessment point in transplantation, readmission rates were examined. Reasons for readmission, as well as sociodemographic and disease and stem cell transplant related variables were evaluated. Predictors of readmission were identified using multivariate regression analysis. Results: 33.6% (42/125) of patients were readmitted within 30 days of discharge. Of patients who survived until day +100, 46.7% (57/122) were readmitted within 100 days of UCBT. The most common cause for readmission was infection (38.3%), followed by fever without a source (14.8%) and graft vs. host disease (GVHD) (8.6%) (Table). A multivariate logistic regression model of the probability of being readmitted within 30 days and by day +100 suggested that infection during transplant admission was a significant risk factor for readmission (OR: 5.1, p=0.003 and OR: 2.9, p=0.014, respectively). Conclusions: There is a high rate of readmission within 30 days and by day +100 following UCBT. The most common causes of readmission were infection and fever without a source. Infection during the transplant admission predicted a higher risk of readmission, suggesting a possible group to target for interventions aimed at reducing readmissions and improving quality of care. [Table: see text]

265 Background: Recent initiatives to improve patient safety and reduce healthcare costs have focused on preventing hospital readmissions. Historically, patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of hospital readmission. The purpose of this study was to identify the incidence and reasons for readmissions in allogeneic HSCT patients as well as associated risk factors for readmission. Methods: A retrospective review of patients receiving a myeloablative or reduced intensity conditioning (RIC) HSCT at Dana Farber/Brigham and Women’s Hospital between January 1, 2005 and December 31, 2010 was performed. Reasons for readmission, along with sociodemographic, disease, and transplant related variables were evaluated. Potential risk factors for readmission were determined by multivariate regression analysis. Results: A total of 1,097 HSCT patients were reviewed. In the myeloablative group, 130 of 495 (26.3%) patients were readmitted within 30 days of discharge, among whom the majority of patients (71.5%) had one readmission. For RICs, 105 of 602 (17.4%) patients were readmitted within 30 days, among whom 62.9% of patients had one readmission. In the myeloablative group, the most frequent reasons for readmission were infection or fever without identified source (40.7%) and graft versus host disease (GVHD) (23.7%). Similarly, the most common diagnoses at readmission in the RICs were infection or fever without source (54.9%) and GVHD (11.0%). In the RICs, a logistic regression model of the probability of being readmitted suggested active disease (OR 2.0, p=0.005), a mismatched donor (OR 2.4, p=0.029), infection during the index admission (OR 5.8, p

185 Background: Health care institutions are identifying strategies to reduce unnecessary testing, employ better utilization of resources, and decrease risk. At Dana-Farber Cancer Institute (DFCI), patients admitted for autologous SCT have standard testing, including CXR, completed within 42 days of hospital admission. Despite previous work-up, routine CXR is often ordered on admission. We questioned if this repeat CXR was clinically necessary. A retrospective review from 2010 showed that 69 of 130 (53%) asymptomatic SCT patients had CXR obtained on the day of admission. Two patients had findings of possible atelectasis vs. infiltrate on admission CXR. No further work up or antibiotics were initiated. After count recovery, one of the two patients had a chest CT for evaluation of fevers, showing only atelectasis. Based on these results, we aimed to reduce admission CXR without clinical indication to less than 5% by July 1, 2012. Methods: A multidisciplinary group was formed to map existing processes leading to admission CXR. Areas where previous standard testing were not readily available and areas of redundancy were identified. Changes to the EMR allowing easier access to pre-transplant results were made and a written and oral education program for PAs and nocturnists was created. Study Population: All elective patients admitted to the bone marrow transplant PA service (BMT-PA) for autologous SCT for multiple myeloma or lymphoma between 11/1/11-5/30/12. Results: The intervention (changing the EMR and establishing an education program) resulted in a reduction of admission CXR in asymptomatic patients from 53.3% to 5.5% (target 5.0%). During the study period, 144 patients were admitted to the BMT-PA service. Of those, 8 had CXR without indication. All CXR were ordered by Nocturnists, two prior to the intervention and six in the last four weeks of the observation period. Conclusions: The reduction of unnecessary CXR in asymptomatic SCT patients has had a considerable reduction in overall costs, nearly $58,000 to date, as well as reduced delays in initiating chemotherapy, radiation exposure, overall resource utilization, and patient inconvenience. Through this simple intervention, this reduction was easily obtained.

Background: Preclnial modelhave demonstrated the effiacy of GM-CSF secreting cancer vaccies (GVAX ) accompanied by vaccine-primed lymphocyte infusion follwing ASCT. Methods: Patints (Pts) < 60 years old wih de novo AML (excluding M3) were enrolled. Leukemia cellwere harvested at diagnosis follwed by induction and consolidation chemotherapy and ASCT. A single pretransplant vaccine composed of irradiated autologous leukemia cells mied with GMCSF gene-modifid K562 cell(CG9962) was given followed by colection of vaccine-primed lmphocytes that were reinfused with the stem cell graft Posttransplant vacciatins were iniiated at week 6 (or upon pltelet engraftment) and given every 3 weeks (10x10 7 tumor cell+ 4x10 7 CG9962 cels) x 8 vaccinatins. Results: 54 pts were enrolld, 45 (83%) achieved a complete remissin, and 27 (50%) proceeded to ASCT. Delayed-type hypersensiiviy (DTH) reactions to autologous tumor were induced post vaccination in 43% of pts and this was associted with a tend toward longer relpse-free survival (RFS) (100% vs. 60%, p = 0.08) wih a medin follw up of 13 months. Antiodis reactive agaist autologous tumor were induced in 33% and against CG9962 cels in 93%, but no correlatin wih relapse was noted. Minimal residual disease (MRD) was monitored by quantitatve analysis of peripheral blood (PB) and bone marrow (BM) for WT-1, a lukemia-associated gene, by RT-PCR. A decrease iWT-1 in PB (medin ~ 1 log) was noted in 69% of pts folowing the singl pretransplnt vaccinatin and this was associated wih longer RFS (80% vs. 0%, p = 0.02). Post transplnt, 75% of pts demonstrated clearance of WT-1 from PB and this was also associated with iproved RFS (90% vs. 20%, p = 0.02). WT-1 remained detectable ithe BM in 63% of pts, most likely representing background expressin in normal hematopoietic