ALBERT

Description: Abstract 4731 Deep vein thrombosis (DVT) and pulmonary embolism (PE) impose a major public health burden in the United States, affecting an estimated 350,000 to 600,000 individuals and accounting for ~100,000 deaths in the United States each year, according to The Surgeon General's Call to Action (CTA) To Prevent Deep Vein Thrombosis and Pulmonary Embolism (2008). In response to this CTA, the National Blood Clot Alliance (NBCA), a national, community-based, non-profit organization dedicated to the prevention, diagnosis, and treatment of thrombosis and thrombophilia, conducted a survey to benchmark DVT/PE awareness among the general public. Little information about the public's knowledge of venous thromboembolism (VTE) is found in the literature, making this one of the most comprehensive, relatively large surveys of its kind. This DVT/PE awareness survey was conducted in November 2009, among a representative cross-section of 500 adults, 〉20 years, participating in online research panels. Among all respondents surveyed, just 21% said that they had heard of a medical condition called DVT (unaided), and, among this group (n=104), 86% correctly identified it as “deep vein thrombosis” on an aided checklist. Among those respondents who had not heard of a DVT or who had made an incorrect checklist selection (n=411), when DVT was identified for them as “deep vein thrombosis,” 29% then said they knew what it was. Among all respondents, just 16% said that they had heard of a medical condition called PE, and, among this group (n=80), 83% identified it correctly as “pulmonary embolism” on an aided checklist. Awareness of specific DVT risk factors and DVT/PE signs/symptoms was low. Results of this survey show that the medical lexicon poses substantial barriers: only 23% of all respondents reported to know what thrombophilia means and just 9% had heard of VTE. Conversely, 8 in 10 of all respondents said that they do know what a blood clot is, and virtually all respondents (98%) said that they believe blood clots can be life-threatening. The leading factors respondents said they believe are risks for causing blood clots included: family history of blood clots (73%), major trauma (71%), major surgery (69%), and being bedridden (68%), while

Description: Abstract 3830 Background: Although the primary care physician (PCP) is often the first point of contact for patients with suspected hematologic malignancy, little is known about hematologic referrals from primary care, including their frequency, the factors that affect choice of specialist, and the quality of information exchanged. Methods: In April 2010, we administered a 34-item questionnaire to a random sample of 190 physicians in the state of Massachusetts identified as PCPs (family practice, general practice, or internal medicine) in the American Medical Association's physician file. PCPs were given the opportunity to complete the survey via post or Internet. An additional mailing was sent to non-respondents, followed by at least two attempts at telephone contact. Physicians were asked for the approximate number of patients seen in the past year with suspected hematologic malignancy, the frequency of formal specialty referral, and informal “curbside” referral. PCPs were also queried about the factors that influence their choice of specialist, and about the information exchange with the specialist; these measures were then analyzed by self-reported PCP characteristics using chi-square statistics. Results: As of August, 2010, 118 physicians had responded (response rate = 62.1%). 67.8% identified themselves as internists, and 61.9% were male. The median reported patient panel size during the prior 12 months was 1800; median percentage of patients ≥ 65 years was 30.0%; median percentage of patients in managed care was 55.0%; and median year of graduation from residency, 1996. PCPs were evenly distributed with respect to academic affiliation (from no affiliation to full-time faculty). The median number (IQR) of patients in the prior 12 months who were suspected of having hematologic malignancy was 5 (3, 10). Among suspected hematologic malignancies, the median number formally referred to a specialist (hematologist or surgeon) was 5 (3, 10), and the median number who received informal “curbside” consult was 0 (0, 0.5). Respondents rated the importance of several factors in their choice of specialist (1 = not important at all to 5 = extremely important). Those factors rated ≥ 3 included reputation of specialist/facility (94.9%), patient's preference for site of care (92.4%), distance of site from patient's home (89.8%), specialist's affiliation with a cancer center (88.1%), practice's affiliation with specialist (82.2%), personal relationship with specialist (79.7%), patient's ability to pay (67.0%), and availability of clinical trials at the referral site (63.6%). The following table summarizes responses to questions about flow of referral information and follow-up: Conclusions: Consultation for suspected hematologic malignancy from PCPs is relatively infrequent, tends to manifest through formal referral as opposed to informal discussion, and is most often affected by specialist reputation and patient preference for site of care. Only about half of our respondents reported providing the specialist with a referral letter or email, which may result in poor quality of referral information. Alternately, a high number reported giving a copy of abnormal test results to their patients to bring to the specialist, which may ameliorate this issue and reflect an ongoing evolution in the patient/provider partnership. Moreover, fairly often, patients have not been to see the specialist upon follow-up with their PCP. This finding seems to reflect patient cancellations rather than a failure in physician systems, suggesting that increases in patient education and personalized follow-up may be the best approach to ensure completion of timely hematologic referrals. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3486 Delayed myeloid engraftment after HCT is a risk for increased morbidity and mortality, especially in patients with splenomegaly (SM) at time of transplant. Time to engraftment and overall survival after HCT have not been well analyzed in patients with prior splenectomy (SP) or splenic irradiation (SI), when compared to patients with normal spleens (NS) or with SM. A total of 9,683 recipients with myeloproliferative diseases and/or myelodysplasia who were reported to CIBMTR after receiving a myeloablative allogeneic HCT between 1990 to 2006 were compared according to the spleen status at transplant: 472 SP; 300 SI; 1,471 SM and 7,440 NS. Recipients of cord blood grafts were excluded. The median age was 39 years for all groups, the SP group had a higher proportion of patients with Karnofsky performance score

Description: Although some trials have allowed matched or single human leukocyte antigen (HLA)–mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients 〈 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.

Description: Abstract 4740 Deep vein thrombosis (DVT) and pulmonary embolism (PE) affect up to 600,000 individuals and account for ~100,000 deaths in the United States each year, according to The Surgeon General's Call to Action (CTA) To Prevent Deep Vein Thrombosis and Pulmonary Embolism (2008). Oncology patients, particularly those who are hospitalized or undergo chemotherapy, are at increased risk for DVT/PE. Mortality is greater among patients with cancer and venous thromboembolism (VTE) than among those with cancer alone. In response to the Surgeon General's CTA, the National Blood Clot Alliance (NBCA), a national, community-based, non-profit organization dedicated to the prevention, diagnosis, and treatment of thrombosis and thrombophilia, conducted a survey to benchmark DVT/PE awareness among the general public and several at-risk patient groups, including oncology patients. The literature contains little information about at-risk patient knowledge, and almost no information about general public knowledge of VTE, making this the first, large survey of both public and at-risk patient awareness of DVT/PE. The survey was conducted in November 2009, among a representative cross-section of 500 adults, 〉20 years, participating in online research panels. For comparison, the identical survey was conducted among a sample of 500 adults, 〉20 years, screened from an online research panel, who had received a cancer diagnosis or experienced recurrence of cancer within the past 6 months, or who were on active cancer treatment. Evaluations comparing survey responses provided by oncology patients who, in connection with their treatment, did require a hospital stay versus those who did not require a hospital stay showed no statistically significant differences in DVT/PE awareness between the two subgroups. Among all oncology patients surveyed, 24% said that they had heard of a medical condition called DVT, compared to 21% of the general public. Among all respondents who said that they knew what a DVT was (unaided) or who were able to correctly identify DVT on an aided checklist, 61% of oncology and 53% of national respondents said they could name DVT risk factors. The most frequently mentioned DVT risk factor was “sitting for a long time” among both the oncology (45%) and national (28%) samples. Among oncology patients who could name DVT risk factors (n=155), 8% named surgery, 1% named cancer treatment. Among national respondents who could name DVT risk factors (n=109), significantly more (79%) said they could name DVT signs/symptoms compared to oncology respondents (63%) who said the same. While not statistically significant, the national sample did show greater recognition of certain DVT signs/symptoms: skin redness/discoloration, 41% national, 21% oncology; leg swelling, 50% national, 31% oncology; and, leg pain, 37% national, 27% oncology. PE awareness was low among both groups, with 15% of all oncology and 16% of all national respondents saying that they had heard of PE. Of those who what said they knew what a PE was (unaided) or identified it correctly from an aided checklist, about one-third of both groups said they could name PE signs/symptoms, with “breathing difficulties” cited most frequently by oncology (69%) and national (73%) respondents. Significantly fewer oncology patients (28%) mentioned chest pain/tightness as a PE sign/symptom, compared to the national sample (57%). About 8 in 10 oncology and national respondents said that they did know what a blood clot is, and virtually all respondents (98%) recognized blood clots as life threatening. DVT/PE awareness/knowledge was low. Despite increased risk, oncology patients demonstrated no greater awareness of DVT/PE than the general public. DVT/PE education, utilizing interventions identified in the Surgeon General's DVT/PE CTA, should target the general public, with special emphasis on at-risk oncology patients to fill gaps relative to increased DVT/PE risks and signs/symptoms. Terms should be further simplified for future public awareness and patient education initiatives. Disclosures: Brownstein: Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.: Data reported from project supported by Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Ansell:Bayer, Inc: Consultancy; Bristol Myers Squibb: Consultancy, Data Safety Monitoring Boards; Daiichi Sankyo: Consultancy; Boehringer Ingleheim: Consultancy; Ortho McNeil: Consultancy; Sanofi Aventis: Speakers Bureau.

Description: T-cell immunotherapy that takes advantage of Epstein-Barr virus (EBV)–stimulated immunity has the potential to fill an important niche in targeted therapy for EBV-related cancers. To address questions of long-term efficacy, safety, and practicality, we studied 114 patients who had received infusions of EBV-specific cytotoxic T lymphocytes (CTLs) at 3 different centers to prevent or treat EBV+ lymphoproliferative disease (LPD) arising after hematopoietic stem cell transplantation. Toxicity was minimal, consisting mainly of localized swelling at sites of responsive disease. None of the 101 patients who received CTL prophylaxis developed EBV+ LPD, whereas 11 of 13 patients treated with CTLs for biopsy-proven or probable LPD achieved sustained complete remissions. The gene-marking component of this study enabled us to demonstrate the persistence of functional CTLs for up to 9 years. A preliminary analysis indicated that a patient-specific CTL line can be manufactured, tested, and infused for $6095, a cost that compares favorably with other modalities used in the treatment of LPD. We conclude that the CTL lines described here provide safe and effective prophylaxis or treatment for lymphoproliferative disease in transplantation recipients, and the manufacturing methodology is robust and can be transferred readily from one institution to another without loss of reproducibility. The current trial was registered at www.clinicaltrials.gov as #NCT00058812.

Description: Abstract 1756 Background: The optimal criteria to determine which patients with diffuse large B-cell lymphoma (DLBCL) should receive central nervous system (CNS) prophylaxis remain controversial. We aimed to characterize patterns of CNS prophylaxis administration in patients with DLBCL in a large multi-institutional database. Methods: The National Comprehensive Cancer Network (NCCN) Non-Hodgkin's Lymphoma Outcomes Database is a prospective cohort study collecting clinical, treatment, and outcomes data for patients at seven participating NCCN centers. Patients who presented between January 1, 2001 and July 1, 2008 with newly-diagnosed DLBCL, without CNS disease at baseline, and who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) within 180 days of diagnosis were eligible for this analysis. We assessed clinical and sociodemographic covariates of receipt of CNS prophylaxis and type of prophylaxis received (either ≥2 doses of intrathecal methotrexate and/or cytarabine or ≥1 dose of systemic methotrexate). Extrapolating from prior studies (e.g., Boehme et al, Ann Oncol, 2007), we defined high-risk features as 〉1 extranodal site involvement, elevated lactate dehydrogenase (LDH), bone marrow involvement, or other high-risk site involvement (orbit, testis, peripheral blood, bone/vertebrae, nasal/paranasal sinuses), and assessed rates of CNS prophylaxis in patients with ≥1 high-risk feature. We also determined rates of CNS recurrence for patients with ≥ 2 high-risk features who received prophylaxis versus those who did not. Results: Of a total of 989 patients with DLBCL (mean age 56; 44.4 % female; 70.2% with low or low-intermediate international prognostic index (IPI) score), 117 received CNS prophylaxis (11.8% [95% Confidence Interval (CI) 9.8%-13.8%]). Considered individually, patients with bone marrow involvement, other high-risk site involvement, 〉1 extranodal site involvement, high versus low IPI score, and advanced stage (III or IV) were significantly more likely to receive CNS prophylaxis (all p

Description: Despite the clear importance of Hedgehog (Hh) signaling in blood vascular development as shown by genetic analysis, its mechanism of action is still uncertain. To better understand the role of Hh in vascular development, we further characterized its roles in vascular development in mouse embryos and examined its interaction with vascular endothelial growth factor (VEGF), a well-known signaling pathway essential to blood vascular development. We found that VEGF expression in the mouse embryo depended on Hh signaling, and by using genetic rescue approaches, we demonstrated that the role of Hh both in endothelial tube formation and Notch-dependent arterial identity was solely dependent on its regulation of VEGF. In contrast, overactivation of the Hh pathway through deletion of Patched1 (Ptch1), a negative regulator of Hh signaling, resulted in reduced vascular density and increased Delta-like ligand 4 expression. The Ptch1 phenotype was independent of VEGF pathway dysregulation and was not rescued when Delta-like ligand 4 levels were restored to normal. These findings establish that Hh uses both VEGF- and Notch-dependent and -independent mechanisms to pattern specific events in early blood vascular development.