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We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients’ overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

We designed a prospective, observational study enrolling patients presenting for treatment of AML at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), function and geriatric health, in 6 groups: 1) the entire cohort, 2) ≥65 years old, 3) high comorbidity burden, 4) intermediate cytogenetic-risk, 5) adverse cytogenetic-risk, and 6) first complete remission with or without measurable residual disease. Patient health and preferences were assessed eight times across 2 years. Time-dependent regression models were used. Among 692 evaluable patients, 46% received HCT with 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality in the entire group and most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity-burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in all groups. While function, social life, performance status, and depressive symptoms were better for those selected for HCT compared to those who were not, these health advantages were lost after receiving HCT. Recipients and non-recipients of HCT similarly ranked and expected cure as main goal of therapy, while physicians expected more cure for the formers. Accounting for health impairments negate survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is due mostly to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT.

Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

We sought to develop a safe and effective outpatient salvage regimen by replacing ifosfamide within the (R)ICE (rituximab, ifosfomide, carboplatin, etoposide) regimen with bendamustine (T(R)EC) via a multicentre phase I/II study for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). Therapy consisted of 60-120 mg/m2 per day bendamustine on days 1 and 2 in combination with carboplatin, etoposide and rituximab (only for CD20+ lymphoma) used in the (R)ICE regimen for up to 2 cycles. The objectives were to define a maximally tolerated dose (MTD) of bendamustine, determine safety and toxicity, assess efficacy, and evaluate impact on stem cell collection. Forty-eight patients were treated of which 71% had refractory disease. No dose-limiting toxicities were observed. The recommended phase II dose of bendamustine was 120 mg/m2 per day on days 1 and 2. Response rates were 85% (70% complete response, CR) in HL, and 65% (40% CR) in DLBCL. Stem cell collection was successful in 30 of 32 patients. The most common non-haematological toxicities ≥grade 3 were febrile neutropenia (8%) and dehydration (8%). The T(R)EC regimen safely yields high response rates, successfully mobilizes peripheral blood stem cells and compares favourably to RICE, offering an effective outpatient treatment option for patients with relapsed or refractory DLBCL and HL.

Context Acute myeloid leukemia (AML) has a median survival of 6-12 months, with no major improvement over the last two decades. AML is a disease of elderly patients. Less-intensive induction therapies increasingly used in older patients, presuming they are more effective/better tolerated than intensive therapies. Objective Compare survival, quality of life (QOL), and function between less-intensive versus intensive therapies. Design, Setting, and Patients We studied a retrospective cohort (n=1,295) treated from 2008-2012 at six institutions, followed by a prospective observational cohort (n=692) treated from 2013-2017 at thirteen institutions. Both cohorts were ages 18-80 years. Main outcome measures Survival estimates were obtained with the Kaplan-Meier method. We used an AML-composite model (AML-CM) assigning higher scores to increasing age, comorbidity burden, and adverse cytogenetics. Less- and more-intensive induction therapies were compared within distinct prognostic groups defined by AML-CM. We used a competing-risk Cox regression model to test the impact of allogeneic transplant (HCT). Prospective QOL and function were compared between less-intensive and intensive groups across time using logistic regression. Results 20% and 21% of patients received less-intensive therapies in the retrospective and prospective cohorts, respectively. In both cohorts, less-intensive therapies were used more often with increasing age, comorbidity burden, and cytogenetic/molecular risks, and also with Karnofsky Performance Status (KPS) ≤ 70%. Retrospective cohort patients with AML-CM scores of 4-6, 7-9, and ≥10, respectively, had significantly higher hazard ratios (HR) for death after less-intensive therapies, independent from receipt of HCT [in HCT-adjusted models, AML-CM=4-6: HR=1.82 (95% CI=1.25-2.63); =7-9: HR=1.67 (95% CI=1.22-2.27); >10: HR=1.32 (95% CI=0.99-1.72)]. Patients aged 70-79 years had similar results [HR=1.37 (95% CI=1.02-1.85), p=0.04]. Higher mortality risks were also seen in the prospective cohort after less-intensive therapies. In models adjusted for age, physician-assigned KPS and physician perceptions of chances of cure, mortality risks were similar between less-intensive and intensive therapies; QOL and function were also similar. Conclusions We did not find that receiving less-intensive induction led to better survival, QOL, or function compared to intensive therapies, including in those aged 70-79 years or with high comorbidity burden. This challenges current practice and demonstrates the need for a randomized trial. This research was, in part, funded by a Patient-Centered Outcome Research Institute award (CE-1304-7451), in part, by a Research Scholar Grant from the American Cancer Society (RSG-13-084-01-CPHPS), and, in part, supported by an American Society for Hematology Bridge Award.

Introduction: Survival rates continue to improve after allogeneic HCT (Gooley et al, NEJM, 2013). Population-based studies also indicate overall improvement in survival of older (60-80 years old) AML patients (pts) (Bower, Blood Cancer Journal, 2016). Yet, only a small minority (6%-8%) of them receive HCT (Medeiros, Ann Hematol. 2015). Given these potentially incongruent findings and the changing face of survival in AML, we designed the first prospective multi-center longitudinal study dating from first presentation of adults with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We compared survival according to whether or not pts received HCT at later time points. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including activities of daily living (ADL); frailty; geriatric assessment including cognition; QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale, ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. We used time-dependent Cox regression analyses to identify baseline and time-dependent risk factors associated with mortality in the overall population. The factors identified as significantly associated with mortality (p Results: Median follow-up was 16.8 months (range 0.1-52.4). In the initial multivariate analyses, the following were identified as significantly associated with an increased risk of mortality (Table 2): HCT-CI scores ≥5 (p Survival after HCT was 58% at 2-years. Initial unadjusted analyses showed significantly lower risks of mortality in association with receiving allogeneic HCT (p=0.0003). These findings were similar in pts with intermediate (p=0.0005) or unfavorable (p However, in the adjusted models, the advantage of HCT in reducing mortality rates was lost both in the overall population (p=0.21, see figure) as well as in the other groups (p>0.54, 0.40, and 0.51, respectively, Table 3). Formal tests of interactions (Table 3) showed no statistically compelling evidence that the association of HCT and mortality varies with respect to the timing of mortality or to the underlying ELN risk. Conclusions: In a prospective observational study, adjusting for key AML-specific and pt-specific variables negated the observed benefit of HCT over non-HCT therapies in reducing mortality rates among AML pts. Our results might reflect 1) improvement in supportive care and non-HCT therapies, 2) a relatively high non-relapse mortality early after HCT and the need for longer follow-up to demonstrate an adjusted benefit of HCT, and 3) the high selectivity of the transplant eligibility process, as we accounted here for variables that are often ignored in "genetic assignment" randomized studies (i.e. comorbidities and function). New randomized trials are needed; however, these trials have to be more inclusive of vulnerable pts and measure pt-specific variables. Trials focusing on reducing burden of comorbidities, frailty and poor function are needed alongside trials to treat AML with or without HCT. Disclosures Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Shami:JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees; Lone Star Biotherapies: Equity Ownership; Pfizer: Consultancy. Rizzieri:Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wang:Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Alexion: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Otsuka: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.

Introduction: Acute myeloid leukemia (AML) is most frequently diagnosed in older patients (pts), whose median survival is less than 1 year. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. However, older pts often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. To this end, we designed a prospective, multi-center, longitudinal, observational study dating from first presentation of adult pts with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including instrumental activities of daily living (IADL) and activities of daily living (ADL); frailty including walk test; geriatric assessment (GA) including cognition; Karnofsky performance status (KPS); QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale (EQ-5D), ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. High-risk myelodysplastic syndromes (MDS) receiving AML-like therapy were included. We used competing risk Cox regression analyses, treating HCT as the event of interest and death without HCT as a competing risk, with staggered entry (left truncation) at time of consent. Associations between variables were assessed both at enrollment and over time. Results: The overall rate of HCT at 9 months after enrollment was 43% (Figure 1) and 92% of pts who received HCT did so by the 9 month mark. In multivariate analyses, death without HCT (Table 2) was associated with augmented HCT-CI scores ≥5 (HR:2.11, p Among survivors (Table 3), low likelihood to receive HCT was associated with age ≥70 years (HR:0.40, p=0.0001), low ELN risk (HR:0.28, p Conclusions: In a prospective, observational, multi-center study, increasing age, comorbidity burden, ELN risk, low-intensity initial AML induction regimen, depression, and functional dependence increase risks of early mortality without HCT. In those who survived long enough to potentially receive HCT, age up to 69 years and/or multiple comorbidities were not found to be barriers to HCT, likely reflecting the widespread use of reduced-intensity conditioning regimens. However, the independent sharp decline in receipt of HCT in pts aged 70-80 years suggests continued bias, although pts in this age group have been shown to derive similar benefit from HCT as younger pts. Use of objective comorbidity and GA tools rather than age per se to decide on HCT is encouraged. The adverse impact of impairments in psychological health and function on survival and of impairments of cognition, geriatric health, and performance status on receipt of HCT emphasize the need for interventions that target these health limitations in conjunction with AML treatment to improve outcomes. Finally, the benefit of intensive vs. less-intensive induction therapies should be addressed with a randomized trial. Disclosures Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Shami:Lone Star Biotherapies: Equity Ownership; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees; JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy. Rizzieri:Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang:Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Amgen: Speakers Bureau; Otsuka: Consultancy; Alexion: Consultancy, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.

Objectives/Hypothesis: To assess the efficacy of paclitaxel, ifosfamide, and cisplatinum induction chemotherapy plus concurrent chemoradiation in the treatment of stage III and IV base of tongue cancer. Study Design: Subgroup analysis of patients with base of tongue cancer enrolled in a single-institution prospective phase II trial, evaluating an organ-preservation approach in the treatment of locally advanced head and neck cancer. Methods: Eighteen patients with tumors ranging from stage T2–T4, any N, or M0 were treated with a protocol of induction chemotherapy, with Taxol, ifosfamide, cisplatin every 21 days for up to three cycles. If the primary tumor exhibited a complete or partial response, patients were treated with radiation and weekly taxol and carboplatin for 7 weeks. Surgery was used for those with less than partial response or disease progression. Neck dissection was performed in cases with clinical or radiological evidence of persistent disease in the neck 6 to 8 weeks after completion of treatment. Results: Sixteen patients were male and two were female; the average age was 55 years (range, 43–65). Fifteen patients had stage IV disease and three had stage III disease. Of the 18 patients initially enrolled, 17 patients had a complete response. All 17 patients had no evidence of loco-regional disease at a median follow-up of 29.6 months. Only 1 of them developed distant metastases 30 months after completion of treatment. Three patients required permanent percutaneous endoscopic gastrostomy tubes because of severe dysphagia associated with concurrent chemoradiation. Conclusions: The treatment regimen studied is remarkably effective in stage III and IV base of tongue cancer with 100% of patients completing the protocol alive to date. Although some patients required persistent percutaneous endoscopic gastrostomy use, no patient experienced significant enough toxicity during the protocol to delay or withdraw from treatment.

Objective. The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT3) antagonists in revolutionizing the management of platinum-based chemotherapy–induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT3 antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting clearly endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. Methods. Data for patients (n¼159) receiving platinum-based chemotherapy regimens were retrospectively collected. Patients getting 5-HT3 antagonists without steroids or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and Eastern Cooperative Oncology Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of >grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic efficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. Results. A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron (n¼157), granisetron (n¼81), and ondansetron (n¼131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p¼0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p¼0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting (p¼0.15 and p¼0.63, respectively). However, complete nausea control was significantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p50.05). Conclusion. No significant difference exists in the antiemetic efficacy of the three 5-HT3 antagonists studied in controlling CINV when administered in combination with dexamethasone. Choice of antiemetic regimen should therefore be based on drug cost.

The aim of this article is to assess the current understanding and uncertainties about the evaluation and management of thrombotic microangiopathy that occurs following allogeneic hematopoietic stem cell transplantation.Current data may not be sufficient to establish posttransplantation thrombotic microangiopathy as a discrete clinical or pathologic entity, distinct from other well recognized transplant-related complications. Analysis of case series of posttransplantation thrombotic microangiopathy illustrates uncertainties regarding incidence, risk factors, diagnosis, treatment, and survival. These studies have suggested the lack of efficacy of plasma exchange treatment and have identified other transplant-related complications, such as acute graft-versus-host disease and opportunistic infections, as the predominant causes of death in patients who had been diagnosed with posttransplantation thrombotic microangiopathy. Recently consensus diagnostic criteria were proposed by two independent groups to provide more uniform identification of patients with posttransplantation thrombotic microangiopathy; these criteria may result in a clearer definition of this syndrome.Posttransplantation thrombotic microangiopathy remains a diagnostic and therapeutic challenge. Further studies are required to determine if it is a specific entity and to define its relation to other transplant-related complications.

The occurrence of microangiopathic hemolytic anemia and thrombocytopenia in patients with disseminated malignant disorders has been well documented. However, when systemic malignancy is not clinically apparent, these features may be misdiagnosed as thrombotic thrombocytopenic purpura–hemolytic uremic syndrome (TTP-HUS), and patients may be treated with plasma exchange, a procedure with substantial risk. Among the 329 patients in the Oklahoma TTP-HUS Registry, 1989–2005, 12 patients who were treated with plasma exchange for presumed TTP-HUS were later found to have a systemic malignancy. Details about one such patient, a 52-year-old woman who had a history of breast cancer, are presented. Although some of her clinical features were atypical for TTP-HUS, and the possibility of recurrent breast cancer was carefully considered, no evidence of cancer was found and plasma exchange treatment for TTP-HUS was initiated. Disseminated breast cancer was not revealed until a microscopic examination of tissue sections was made at autopsy. In retrospect, a bone marrow biopsy might have documented the presence of metastatic cancer in this patient. Hematologists/ oncologists must be aware that patients with clinically diagnosed TTP-HUS may have an occult systemic malignant disorder.

We define chronic refractory immune thrombocytopenic purpura (ITP) as ITP with persistent thrombocytopenia following treatment with glucocorticoids and splenectomy. Chronic refractory ITP is uncommon, occurring in fewer than 10% of all adult patients with ITP diagnoses. The goal of treatment is only to achieve a safe platelet count with minimal treatment-related risk. A safe platelet count may be considered to be as low as 10,000/microL, because the risk for major bleeding in otherwise healthy subjects is great only when the platelet count is less than 10,000/microL. Observation without specific treatment is appropriate for patients with moderate thrombocytopenia and no clinically important bleeding symptoms. For patients with chronic refractory ITP who require treatment, there is no consensus for what therapies to use or the sequence in which to use them. For patients with severe and symptomatic thrombocytopenia, the use of anti-CD20 (rituximab) and immunosuppressive agents, alone or in combination, may be most effective. The mechanism of all current therapies is to decrease the accelerated platelet destruction brought about by immunosuppression. An alternative approach, the stimulation of platelet production with thrombopoietic agents, has been successful in investigational studies and may provide a new management option.

Chronic refractory idiopathic thrombocytopenic purpura (ITP) is defined as ITP with persistent thrombocytopenia despite conventional initial management with prednisone and splenectomy. Rare in children, it may occur in as many as one third of adults with ITP. The goal of treatment is not cure of the ITP, but only to achieve a safe platelet count, which is arbitrarily assumed to be greater than 30,000 to 50,000/μL. The risk for major bleeding seems great only when the platelet count is less than 10,000/μL. Treatment of patients with moderate thrombocytopenia and no clinically important bleeding symptoms should be avoided. There is no accepted algorithm for management of patients with chronic refractory ITP. Observation without specific treatment must be considered a cornerstone of management. Combination regimens of immunosuppressive agents may be required for patients with severe and symptomatic thrombocytopenia. Additional supportive care measures are also important.

Background: Chemoimmunotherapy regimens remain the preferred first-line treatment for most of patients with CLL/SLL. Recent studies have demonstrated the efficacy of maintenance regimens by improving progression-free survival (PFS). We studied safety and efficacy of a treatment protocol that included induction and maintenance components using vorinostat, a histone deacetylase inhibitor, in combination with FCR for induction and with rituximab for the maintenance. Methods: Previously untreated CLL/SLL patients with indication for treatment were eligible. Primary objective of the Phase I part was the maximum tolerated dose (MTD) of vorinostat that could be combined with FCR and PFS was the primary endpoint for phase II. In the induction phase, FCR (fludarabine 25 mg/m2 days 1-3, cyclophosphamide 250 mg/m2 days 1-3 and rituximab 375 mg/m2 on day 1 of cycle 1 and 500 mg/m2 on day 1 of subsequent cycles) was given every 28 days for 6 cycles. In addition to FCR, patients received vorinostat orally on days 1-5 and days 8-12 of each treatment cycle. In the dose finding phase, vorinostat was given at 3 dose levels: 200 mg, 300 mg and 400 mg PO daily. There was no dose limiting toxicity and 400 mg was chosen as the MTD for phase II. Patients who received at least 4 cycles of induction were eligible to receive maintenance beginning within 3 months of the last cycle of FCR. In the maintenance phase, given every 3 months for 8 cycles, rituximab was given at dose of 500 mg/m2 on day 1 and vorinostat was given at 400 mg PO daily on days 1-14 of each cycle. Results: 40 patients (CLL 32, SLL 8) were treated. Median age was 58 years (36-72). Median time from diagnosis to treatment was 27 months (0 -102). Rai stage at the time of treatment was I/II in 23 (60%) and III/IV in 17 (40%) patients. Cytogenetic (CG) abnormalities included del17p in 2 (5%), del11q in 2 (5%), trisomy 12 in 4 (10%), del13q in 3 (7.5%), normal CG in 14 (35%) and other abnormalities in 6 (15%) patients. Median number of induction cycles was 6 (1-6) and 33 patients (83%) patients finished at least 4 cycles of induction and were eligible for maintenance. Reasons for delivery of less than 4 induction cycles were patient preference (2), GI toxicity (1), thrombocytopenia (1), pulmonary emboli (1), progressive disease (1) and sepsis (1). Twenty-six patients (65%) received at least 1 cycle of maintenance treatment (median 8; range, 1-8) and 15 patients (40%) finished all 8 planned maintenance cycles. Eleven patients started maintenance treatment but did not receive all 8 maintenance courses due to neutropenia (3), patient preference (3), infections (1), insurance issues (1) or other reasons (3). Six patients (15%) were eligible for maintenance but did not receive it because of hematologic toxicities (3), infection (1) or patient preference (2). Overall response rate after induction was 91% with CR in 26 (74%), PR in 4 (11%), nPR in 2 (6%) and stable disease (SD) in 1 (3%). One patient (3%) had progressive disease during the induction and 1 (3%) was not evaluable. Twenty-one of 23 (88%) patients who achieved CR after induction, were tested for minimal residual disease (MRD) by flow cytometry and cytogenetics and 21 (91%) had negative MRD status. One of 2 CR patients who was MRD positive after induction converted to MRD negative after maintenance. After median follow-up of 42 months, 5-year estimate of overall survival was 90% (95% CI 75%-96%) and 5-year estimate of PFS was 72% (95% CI 51%-85%). None of the patients who achieved CR after induction (n=26; 74%) had disease progression after median 46 months of follow-up while 3 of 6 patients with PR or nPR had disease progression which occurred median of 40 months (29-51). Most common grade 3-4 toxicities were hematologic (36%), electrolyte abnormalities (9%), gastrointestinal (8%) and cardiovascular (6%). 4 patients (10%) died during the follow-up because of disease progression (1), sepsis (1), fungal infection (1) and suicide (1). Median time to death was 9.5 months (5 -20). Conclusion: Combination of vorinostat with FCR for induction and with rituximab for maintenance was feasible and effective with a high ORR and long OS and PFS with no relapses observed among patients who achieved CR after induction. Cytopenias and infections were main reasons for treatment discontinuation especially during the maintenance phase. Combination of novel agents with conventional induction and maintenance regimens is a promising strategy for treatment of CLL/SLL. Disclosures Shadman: Gilead: Honoraria, Research Funding; Emergent: Research Funding; Acerta: Research Funding; Pharmacyclics: Honoraria, Research Funding. Gopal:Paid Consultancy- Gilead, Janssen, Seattle Genetics, Spectrum, Research funding- Gilead, Janssen, Pfizer, BMS, Merck, Teva, Takeda, Spectrum, Seattle Genetics: Consultancy, Honoraria, Research Funding. Press:Roche / Genentech: Consultancy, Research Funding. Maloney:Juno Therapeutics: Research Funding; Genentech/Roche: Consultancy, Honoraria.

The goal of initial treatment for transplant eligible patients with multiple myeloma (MM) is to achieve the deepest possible response in an effort to attain prolonged event-free survival after transplant. There has been an excellent response to the three-drug regimens of agents approved for upfront use (Table 1), including bortezomib/IMiD (thalidomide or lenalidomide) dexamethasone (VTD or VRD) and bortezomib/cyclophosphamide/dexamethasone (VCD). We had previously treated patients with three cycles each of two sequential three-drug regimens, VCD, then VTD, and reported an overall response rate of 92%, with a CR rate of 26%.1 Another three-drug regimen, liposomal doxorubicin/bortezomib/dexamethasone (DVD) also resulted in a good overall response rate of 71.5%⩾PR, and 20% CR in previously untreated patients.2 Our objective in developing the bortezomib, cyclophosphamide, pegylated liposomal doxorubicin and dexamethasone regimen was to improve the depth of response and overall response rate compared to three-drug regimens. In addition, the study was designed to improve ease of administration by use of weekly dosing rather than the typical twice weekly dosing (that is, days 1, 4, 8 and 11) of bortezomib (the standard dosing at study inception). The efficacy of this four-drug regimen was examined in newly diagnosed, transplant eligible patients, with a secondary objective of evaluating rates of successful stem cell mobilization and survival after transplant.

Background. Posttransplantation thrombotic microangiopathy (PTMA) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, limited autopsy data are available, and it remains unclear whether PTMA is a discrete clinical and pathologic entity. The aims of this autopsy study were to determine the correlation between clinical and pathologic diagnosis of PTMA, to define the precise morphologic spectrum of PTMA, and to seek for potential etiologic factors. Methods. The study included 20 consecutive patients with HSCT autopsied at the University of Oklahoma, between 1994 and 2005. Applying strict clinical-laboratory criteria, 6 patients were diagnosed clinically with PTMA and treated with plasma exchange. Clinical variables, including underlying disease, conditioning regimen, stem cell donor status, duration and serum level of cyclosporine, infections, and acute graft versus host disease were compared statistically in patients with histologic signs of PTMA (n= 8) with those without PTMA (n= 12). Results. PTMA was verified histologically in all 6 patients with a clinical diagnosis ofPTMA but only 2 of the 14 patients who were not clinically diagnosed had histologic evidence of PTMA (P

8533 Background: Traditional multi-agent salvage strategies for lymphoma are less effective after failed modern front line therapies. Bendamustine (Treanda, T) has considerable anti-lymphoma activity and a favorable toxicity profile. We hypothesized that bendamustine could replace ifosfamide within the (R)ICE regimen yielding a feasible and effective salvage strategy (TREC). Methods: This multicenter phase I study used a two stage design followed by 2 expansion cohorts for patients with diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Eligibility included measurable relapsed/refractory lymphoma, ECOG performance status ≤ 2, adequate blood counts and organ function. The primary objective was to define a maximally tolerated dose (MTD) of bendamustine associated with a dose limiting toxicity (DLT) rate of ≤ 25%. Therapy consisted of bendamustine ranging from 60 mg/m2 to 120 mg/m2 daily on days 1 and 2 with standard doses of carboplatin, etoposide, and rituximab (CD20+ disease only) used in th...

The rationale for immunosuppressive therapy of thrombotic thrombocytopenic purpura (TTP) was established by observations that TTP may be caused by autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13 may have a higher mortality, and survivors may require prolonged plasma exchange therapy in spite of adjunctive glucocorticoid treatment. More intensive immunosuppressive therapy with rituximab may provide benefit for many of these patients. The Transfusion Medicine/Hemostasis Clinical Trials Network is developing a randomized, clinical trial to test the hypothesis that addition of rituximab to standard treatment of TTP with plasma exchange and glucocorticoids will decrease initial treatment failure rates as well as subsequent relapses over the following 3 years. To provide the background data for this clinical trial, a systematic review of all published reports on rituximab treatment of immune-mediated disorders was performed. Twelve articles have reported 27 patients treated with rituximab for TTP, with benefit described in 25 (93%) of the patients. Additional reports have described rituximab treatment of 37 other immune-mediated disorders, with clinical response in most patients. These observations from small uncontrolled case series provide the background and rationale for a randomized clinical trial to establish the role of rituximab in the management of patients with TTP.

Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is thought to be uncommon and to have a good prognosis.To describe the frequency, clinical features, and long-term outcomes of quinine-associated TTP-HUS.Case series.Hospitals in central-western Oklahoma.225 consecutive patients with TTP-HUS, 1989-2000.Presenting features and clinical outcomes.Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was associated with quinine in 17 patients. Four patients died, and 7 survivors currently have chronic renal failure. Since 1 July 1995, 132 patients with clinically suspected TTP-HUS were explicitly asked about drug exposure. Fourteen (11%) had taken quinine, and 7 had taken other drugs associated with TTP-HUS. Neurologic abnormalities were as severe in patients with quinine-associated TTP-HUS as in the 118 patients who had not taken quinine.Quinine is a common cause of drug-associated TTP-HUS and can cause death and chronic renal failure. When the disorder is described as TTP-HUS rather than only as HUS, the severity of neurologic abnormalities and the occasional absence of renal failure are emphasized. If recurrent disease is to be prevented, clinicians must recognize quinine as a possible cause.

Background The limitations of current CLL/SLL treatments include suboptimal response rates, variable remission durations, toxicities, and few cures. Vorinostat is a histone deacetylase inhibitor that regulates gene transcription and possibly CD20 expression, leading to its investigative use in the treatment of B-cell malignancies. For this reason, we studied the addition of vorinostat to fludarabine, cyclophosphamide and rituximab (FCR+V) followed by maintenance therapy with rituximab and vorinostat. Methods Patients over age 18 with previously untreated Rai stage I-IV CLL or SLL and ECOG 0-2 were eligible. They received 4-6 cycles of FCR+V followed by up to eight cycles of maintenance with rituximab and vorinostat. Each cycle of FCR used cyclophosphamide 250 mg/m2 IV on days 1-3 and fludarabine 25 mg/m2 IV days 1-3 of each cycle given every 28 days; with rituximab 375 mg/m2 IV once with cycle 1 followed by 500 mg/m2IV once per cycle for cycles 2-6. Rituximab 500 mg/m2 IV was given day 1 of each 3 month cycle of maintenance for up to 8 cycles. Vorinostat was given on days 1-5 and 8-12 of each treatment cycle and days 1-14 of each 3-month maintenance cycle. The Phase I vorinostat starting dose was 200 mg/day and escalated by 100 mg/day to a maximum pre-determined dose of 400 mg/day in a 3 x 3 design. Since no dose limiting toxicity was seen during Phase I, the previously designated maximum dose of 400 mg/day vorinostat was chosen for the Phase II portion of the trial. Results Ten patients were treated on the Phase I portion of the study, and 26 patients have been enrolled in the Phase II portion at the maximum vorinostat dose of 400 mg/day combined with FCR and rituximab maintenance. The median age of patients on study was 58 (range, 36-72); with 6 patients enrolled with Stage I, 15 with Stage II, 5 with Stage III and 10 with Stage IV disease. Nine patients (25%) had >30% CD38 expression, 13 patients (36%) had >20% ZAP70 expression, and 4 patients (11%) had 17p deletions detected by FISH of marrow samples. Median follow-up on study is 15 months (range, 0.9-38.6). Of the 36 patients enrolled, 22 patients are evaluable after completing 4-6 cycles of FCR+V, 1 patient progressed after cycle 2 (del17p), 9 patients are currently receiving FCR+V and 4 patients are unevaluable. Of these 4 patients, one withdrew voluntarily, one was taken off study due to non-compliance, one went off study after cycle 3 due to cytopenias, and one patient with multiple co-morbidities died of sepsis after cycle 5. Of the 22 patients who have completed 4-6 cycles of FCR+V, 16 (73%) obtained a complete response (CR), 5 (22.5%) obtained a partial response (PR), and 1 (4.5%) has stable disease. Of these 22 patients, 4 (18%) have completed 8 cycles of maintenance with rituximab and vorinostat, 5 (23%) were taken off study due to cytopenias, 1 (4.5%) went off study due to insurance issues, 1 (4.5%) went off study due to recurrent infections, 2 (9%) voluntarily withdrew from study, and 9 (41%) are still receiving maintenance therapy. The most common grade 3-4 non-hematologic toxicities during FCR+V were gastrointestinal symptoms in 10 patients and fatigue in 3 patients. However, there were no grade 3-4 non-hematologic toxicities that resulted in patient withdrawal from study during treatment with FCR+V. No grade 3-4 non-hematologic toxicities have been observed in patients who have completed or are undergoing maintenance with rituximab and vorinostat. Conclusion Treatment of CLL/SLL with fludarabine, cyclophosphamide, rituximab and 400mg/day vorinostat (FCR +V) followed by maintenance with rituximab and vorinostat appears feasible and tolerable, and may warrant further study. Disclosures: Gopal: Merck: Research Funding. Press:Roche/Genentech: Consultancy.

Abstract 5038 Background: Combination regimens have been highly effective in multiple myeloma. Based on our results with the combination of bortezomib, cyclophosphamide, dexamethsone (Bensinger et al Br J Haematol 2010), we added liposomal doxorubicin to assess whether we could improve response as well as evaluate a weekly combination regimen at our academic center and network affiliated sites in the community. The trial is registered as NCT00849251. Methods: We initially evaluated the regimen in the relapsed setting for toxicity and found it to be well tolerated in 6 patients, then moved to newly diagnosed patients, with the intent that the regimen would serve as induction chemotherapy in preparation for autologous stem cell transplant for transplant-eligible patients. The dosing was bortezomib 1. 6 mg/m2 IV, cyclophosphamide 300 mg/m2 IV, and dexamethasone 40 mg po, days 1, 8, 15, and a single dose of liposomal doxorubicin 30 mg/m2 on day 8 per 28 day cycle. Patients received a maximum of 4 cycles of therapy and the primary endpoints were safety and response at the end of treatment. Results: A total of 31 out of the planned 45 patients (both newly diagnosed and relapsed) were enrolled, as the trial was ended early due to inability to obtain liposomal doxorubicin (Doxil®) for a period of 6 months. One of the relapsed patients was administratively withdrawn after the cycle 1 day 1 treatment. For the remaining 5 relapsed patients who received 2–4 cycles of treatment, the responses were 1 VGPR that was only immunofixation positive, 1 PR and 3 stable disease (SD). For the 24 patients with newly diagnosed MM who completed 1–4 cycles of treatment, there were 2 complete remissions (CRs), 5 VGPRs (2 of which were only immunofixation positive), 11 PRs, and 6 SD for an overall (CR+VGPR+PR) response rate of 75%. Five patients did not complete 4 cycles of therapy, one due to massive pulmonary embolism, one because of need for radiation for intractable back pain during cycle 2 despite marked serological response, and 3 due to stable disease with plateau in response. Of the 25 patients who received BCDD as initial therapy, there have been 3 deaths to date, one due to massive pulmonary embolism on day 13 of the first cycle of treatment, without known history of hypercoagulable risk, one at 7. 7 months of unknown cause, and one at 15. 3 months of progressive disease, resulting in an estimated overall survival of 86% at 2 years from start of therapy. Median follow-up among the 22 survivors is 16. 6 months (range, 8. 1 to 26. 8 months). One patient with a known central line associated deep venous thrombosis in the relapsed group did not exhibit progression of thrombosis off warfarin during therapy. After enrollment of the first 9 patients, an amendment was filed for subsequent patients to receive aspirin prophylaxis, or if at high risk by criteria suggested by Palumbo et al for prophylaxis for MM patients on imids, with low molecular weight heparin or warfarin. Other adverse events that were attributed to investigational regimen include grade 3 hand/foot syndrome (2), infection without neutropenia (1), urinary tract infection (1), and gastrointestinal hemorrhage due to Mallory-Weiss tear (1). Twenty-one patients who completed therapy went on to successful mobilization and collection of peripheral blood stem cells, and autologous or tandem autologous (2) or tandem autologous-minimal myeloablative allogeneic stem cell transplant (7). Two of the 21 patients have died (one at 2. 1 months after first autologous transplant from unknown cause, and one at 9. 8 months from progressive disease). Median follow-up after first autologous transplant among the 19 survivors is 13. 4 months (range, 1. 1 to 20. 4 months). Summary: The 4 drug BCDD regimen exhibited a 75% overall response rate after 4 cycles, with no progression during treatment, was able to be administered weekly in an outpatient setting of both academic and community hematologists and oncologists, and successfully prepared patients for autologous stem cell transplant. Disclosures: Becker: Millennium: Research Funding. Bensinger:Millennium: Research Funding.

Abstract 3650 Background: Traditional salvage strategies for relapsed lymphoma are less effective when disease recurs after modern front line therapies (e.g. R-CHOP, BEACOPP). Furthermore, typical multi-agent regimens require inpatient hospitalization and carry the risk of significant non-hematologic toxicity from drugs such as ifosfamide, high-dose cytarabine, and cisplatin. Bendamustine (Treanda ®, T) has both broad spectrum clinical activity in lymphoma and a moderate side effect profile, though limited data exist on the utility of this agent as part of a dose-intense rescue approach. We, thus, hypothesized that bendamustine could safely supplant ifosfamide within the RICE regimen yielding a feasible, effective, outpatient multi-agent salvage strategy (TREC) for patients with relapsed or refractory lymphoma. Methods: Eligibility included: relapsed/refractory lymphoma (untreated T-NHL or MCL was allowed during stage 1), age ≥18 years, performance status of 0–2, measurable disease, no active CNS involvement, ANC 3 1,500/μL, platelets 3 100,000/μL, adequate hepatic and renal function, no active arrhythmias, and no known HIV. The primary objective of the study was to define a maximally tolerated dose (MTD) of bendamustine associated with a dose limiting toxicity (DLT) rate of ≤25%. A DLT was defined as any related non-hematologic grade ≥4 adverse event (AE), or inability to complete one full cycle of therapy due to toxicity. Therapy was delivered in the outpatient setting and consisted of bendamustine ranging from 60 mg/m2 to 120 mg/m2 daily on days 1 and 2 in combination with carboplatin (AUC = 5 on day 1), etoposide (100 mg/m2 on days 1 to 3) and rituximab (375 mg/m2, for CD20+ disease only on either day 2 or 3) every 21 days for up to 2 cycles with G-CSF support. Single patient dose escalation occurred until a DLT was observed, followed by cohorts of 4 patients up to a maximum dose of 120mg/m2 × 2. Response was measured by standard criteria (Cheson 2007). AEs were graded using the CTCAE v4.0 Results: Twenty-four patients were treated, 4 in stage 1, and 20 in stage 2 with no DLTs observed. Baseline features included median age = 58 (range 18 – 72) years, median prior therapies = 1 (range 0 – 2), and refractory to last regimen = 16 (of 22 evaluable, 73%). All B-NHL patients had disease progression following prior rituximab. Histologies included Hodgkin lymphoma (HL, n = 8), diffuse large B-cell (DLBCL, n = 9), mantle cell (n = 2), T-NHL (n = 2), follicular (n = 2), and lymphoplasmacytic lymphoma (n = 1). Twenty-three patients received 2 cycles and one received 1 cycle due to disease progression. All cycles were given in the outpatient settings. Thirteen non-hematologic AEs ≥ grade 3 (SAEs) were observed in 9 patients. The most common related SAEs were dehydration (2), and febrile neutropenia (2). Responses were observed in 16 patients (67%) with 9 CR, and 7 PR. Response rates in HL and DLBCL were 88% (6CR, 1PR), and 56%. Mobilization of peripheral blood stem cells (PBSC) was successful in all 15 attempts immediately following the second cycle of T(R)EC (median yield: 5.58×106CD34/kg, range 3.96 – 11.68). At the last update with a median follow up of 8 (range 2 – 18) months, 19 (79%) patients are alive, and 13 (54%) are progression free, including 10 of 12 who subsequently underwenttransplant. Conclusions: This multicenter phase I trial confirms the ability to safely replace ifosfamide with 120mg/m2 × 2 of bendamustine, yielding the TREC regimen for patients with relapsed/refractory lymphoma. The outpatient administration, manageable toxicity profile, effective use for PBSC mobilization, and preliminary response data are encouraging. These data support future evaluation of TREC, including our ongoing expansion cohorts further investigating outcomes in patients with DLBCL and HL. Disclosures: Budde: Teva: Research Funding. Gopal:TEVA: Research Funding.

e13537 Background: DM is the most common cause of kidney disease in the US, and it may increase the risk of CIN. In vivo studies however suggest that DM not only is not a risk factor for CIN, it may even be protective. This may be explained by dysfunction of organic cation transporter-2, the critical transporter for cisplatin uptake in proximal tubules, in diabetic kidneys. We conducted a case-control study to assess the relationship between DM and CIN. Methods: Records of all patients (pts) who received cisplatin between 1/1/00 and 12/31/06 at Oklahoma City VA Hospital were reviewed. DM was diagnosed if pt had (1) been taking anti-diabetic treatment, or (2) Hgb A1C ≥6.5%, or (3) ≥2 fasting outpatient serum glucose levels 126–199 mg/dl, or (4) ≥1 serum glucose level ≥200 mg/dl at any time, prior to receiving cisplatin. CIN was defined as increase in serum creatinine (SCr) by ≥50% above baseline and higher than upper limit of normal, after exclusion of other causes of elevated SCr, during or within 8 weeks of completion of treatment. Continuous variables are reported by means and ranges, and compared using 2-tailed student's t test. Odds ratio (OR) was calculated to compare risk of CIN between diabetics and non-diabetics. Results: Two hundred pts (2 females, 198 males) received cisplatin in the study period, 50 (25%) were diabetic. Distribution of age (years, diabetics: 62 [46–77]; non-diabetics: 60 [26–79], p = 0.18) and baseline SCr (mg/dl, diabetics: 1.0 [0.4–1.5]; non-diabetics: 1.0 [0.5–1.6], p = 0.86) were similar between the two groups. Overall 15% of pts (30 of 200) developed CIN. Risk of CIN was not different between diabetics (8 of 50 pts, 16%) and non-diabetics (22 of 150 pts, 14.7%); OR = 1.11 (95% CI = 0.46 to 2.67) (Table). Conclusions: DM was not shown to be a risk factor for development of CIN. This finding is consistent with in vivo data obtained through animal diabetic models. [Table: see text] No significant financial relationships to disclose.

14132 Background: To assess whether the administration of celecoxib, a specific cyclooxegenease-2 (COX-2) inhibitor, to patients with breast cancer alters the proliferative and apoptotic indexes of their tumors. Methods: Women newly diagnosed with non metastatic breast cancer were enrolled into the study after undergoing a diagnostic core needle biopsy. Patients received celecoxib treatment at 400 mg orally twice a day for 14 days, and then underwent surgical excision of their tumor. Core biopsies obtained at the time of initial diagnostic procedure and surgical excision specimens were stained for Ki-67, as well as COX-2 and cleaved poly (ADP-ribose) polymerase (PARP) expression (as an apoptosis marker). Appropriate negative and positive controls were included. We assessed the difference in Ki- 67, COX-2 and cleaved PARP expression levels, before and after treatment using the Wilcoxon’s matched-pair ranks test and the McNemar’s test. Results: 16 patients were enrolled. The median age was 54.6 years. ER and/or PR expression was present in 81% of tumors; Her-2 neu overexpression was present in 25%. No significant change in COX-2 or cleaved PARP expression was noticed in the post intervention specimen compared to the core biopsies. Surprisingly, there was a significant increase in the Ki-67 expression (p < 0.009). Conclusions: we have conducted a short term prospective study to assess the effects of celecoxib, on the proliferative and apoptotic indexes in patients with early stage breast cancer. We have found an increase in the Ki-67 activity, with no significant down regulation of COX-2 or increase in cleaved PARP expression with 14 days of therapy. This could be partly due to the small sample size. [Table: see text]

6734 Background: High-dose chemoRx→ BM/PSCT is an acceptable salvage for pts with R/R-HL. In a reported single institution(Bierman PJ.et al. Ann Oncol. 2002;13:1370), low albumin (

8056 Background: Chemotherapy-induced nausea and vomiting (CINV) is usually classified as acute (within 24hrs), delayed (>24hrs) and anticipatory. 5-Hydroxytryptamine-3 receptor (5-HT3) antagonists...

Background: multiple myeloma (MM) remains an incurable disease that accounts for approximately 10% of all hematologic cancers. Patients (pts) with MM treated with conventional chemotherapy have a median overall survival of 36–42 months. Various adverse prognostic factors have been described in MM, including elevated B2 microglobulin, hypoalbuminemia, cytogenetic abnormalities of chromosome 13 (13q14 del, monosomy 13), and elevated CRP among others. BCL-2 mediates anti-apoptotic pathways and its expression has been implicated with lack of response to certain chemotherapeutic agents and unfavorable prognosis in different human malignancies. Objective: to evaluate the prognostic significance of BCL-2 expression in patients with MM. Methods: adult pts who were diagnosed with MM at our institution since 1/1/90 were retrospectively analyzed. Expression of BCL-2 was determined by immunohistochemistry (IHC) staining of deparafinized bone marrow specimens. Median survival was calculated for BCL-2 (+) and BCL-2 (−) groups. Survival curves were estimated according to the Kaplan-Meier method, and were compared with the use of the log-rank test. Median survivals were also compared by using Wilcoxon-Mann-Whitney test. Two-tailed alpha level of 0.05 was considered statistically significant. SAS® software (Cary, NC) was used for statistical analysis. Results: sixty-six patients were initially identified. Forty-four pts were excluded because bone marrow samples were not available for IHC staining. Twenty-two pts (11 males, 11 females), with a median age at the time of diagnosis of 64 years (range: 46 to 83 years) were included for this analysis. Fourteen pts (64%) had positive BCL-2 bone marrow specimens, including 4 mild, 3 moderate, and 7 strong staining, while for 8 pts (36%), bone marrow specimens did not stain for BCL-2. Twelve pts (86%) from BCL-2 (+) group and 4 pts (50%) from BCL-2 (−) group died during the period of follow-up; 8 pts are still alive at the time of this analysis, 23 to 71 months (median: 39 months) after diagnosis. The median survival among BCL-2 (+) pts was 35 months (95% CI: 24 – 69 months) and among BCL-2 (−) pts was 47 months (95% CI: 13 months - N/A). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8256 and 0.7072, respectively). Conclusion: although our study did not show correlation between BCL-2 expression and overall survival, median survival among BCL-2 (−) pts with MM was 34% longer than BCL-2 (+) pts. The authors recognize the limitations associated with this analysis including the retrospective nature of the study, small sample size, and exclusion of a large number of patients. This study highlights the need for prospective evaluation of the prognostic significance of BCL-2 expression among pts with MM.

Background: High-dose chemo(radio)therapy (HDC) followed by auto-BM/PSCT is considered an acceptable therapeutic option for patients (pts) with R/R-HL. Various adverse prognostic factors have been previously described in this setting, including resistance to salvage therapy, active disease at the time of transplant, decreased performance status, B symptoms, extranodal disease, and complete remission duration of less than 1 year. On the other hand, overweight state (defined as BMI > or = 28) was associated with reduced overall and event-free survival among pts who received HDC followed by auto-BM/PSCT for non-Hodgkin’s lymphoma. The prognostic significance of excess body weight among pts with R/R-HL who undergo HDC followed by auto-BM/PSCT has not been reported. Objective: To evaluate the relationship between excess body weight and overall survival (OS) in pts with R/R-HL who receive HDC followed by auto-BM/PSCT. Methods: A retrospective, single institution study of consecutive pts with R/R-HL who received HDC followed by auto-BM/PSCT at the University of Oklahoma over the last 19 years (1985– 2004) was performed. BMI was calculated as [weight (kg)/height2 (m)]. Overweight state was defined as BMI > or = 28. OS was defined as the time period in months from the day of transplant until death, or the last of day of follow-up. Survival curves were estimated according to the Kaplan-Meier method, and were compared between the two groups (control group [BMI < 28] and overweight group [BMI > or = 28]) with the use of the log-rank test. Median survivals of the two groups were also compared by using Wilcoxon-Mann-Whitney test. A two-tailed P-value of < 0.05 was considered statistically significant. SAS® sofware (version 8.0; Carry, NC) was used for statistical analysis. Results: 66 pts (40 males, 26 females) were identified, who were 13–69 years old (median 29 years) at the time of transplant. 40 pts (61%) died during follow-up, 4 pts (6%) were lost to follow-up at 15, 27, 58 and 103 months after transplant, and 22 pts (33%) are alive at the time of this analysis (7/30/04), 2–187 months (median 68 months) after transplant. 65 pts were included in this analysis (BMI could not be calculated for one pt). OS for the control group (n1= 42, 26/42 died) was 30 months (95% CI: 20–69 months) and for the overweight group (n2=23, 14/23 died) was 42 months (95% C.I. 8.0- N/A months). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8109 and 0.7367, respectively). Conclusion: Excess body weight is not a prognostic factor in patients with R/R-HL who undergo HDC followed by auto-BM/PSCT. A prospective study to evaluate and confirm our findings is warranted.

Background: Management of R/R-HL has been disappointing with salvage chemotherapy alone. Although controversy remains over the best time to perform a transplant, auto-BM/PSCT is considered an acceptable salvage therapeutic option for patients (pts) with R/R-HL. Hypoalbuminemia is one of the seven adverse prognostic factors for newly diagnosed pts with HL who receive chemotherapy according to the international prognostic factors project on advanced HL. The prognostic significance of hypoalbuminemia in pts with R/R-HL undergoing salvage auto-BM/PSCT is less clearly defined at the present time. Objective: To evaluate the prognostic significance of hypoalbuminemia in pts with R/R-HL who undergo salvage auto-BM/PSCT. Methods: A retrospective, single-institution study of consecutive pts with R/R-HL who received auto-BM/PSCT at the University of Oklahoma over the last 19 years (1985– 2004) was performed. The serum albumin level during hospital admission for transplant that was closest to, but before, high-dose chemotherapy was recorded and used for this analysis. Hypoalbuminemia was defined as a serum albumin level < 3.5 g/dl. Overall survival (OS) was defined as the time period in months from the day of transplant until death, or the last day of follow-up. Survival curves were estimated according to the Kaplan-Meier method, and were compared between the two groups (control group [≥3.5 g/dl] and low albumin group [< 3.5 g/dl]) with the use of the log-rank test. Median survivals of the two groups were also compared by using Wilcoxon-Mann-Whitney test. One-sided P-value of < 0.05 was considered statistically significant. SAS® sofware (version 8.0; Carry, NC) was used for statistical analysis. Results: 66 patients (40 males, 26 females) were identified, who were 13–69 years old (median 29 years) at the time of transplant. 40 pts (61%) died during follow-up, 4 pts (6%) were lost to follow-up at 15, 27, 58 and 103 months after transplant, and 22 pts (33%) are alive at the time of this analysis (7/30/04), 2–187 months (median 68 months) after transplant. Median survival for the control group (n1=27, 13/27 died) was 78 months (95% CI: 23 - N/A months) and for the low-albumin group (n2=39, 27/39 died) was 22 months (95% CI: 13– 44 months). The difference between overall survival curves (figure) and also the difference between median survivals approached, but did not reach statistical significance (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.0632 and 0.0565, respectively). Conclusion: Our results suggest a trend for a worse outcome among pts who undergo salvage auto-BM/PSCT for R/R-HL with low serum albumin ( Figure Figure

9623 Background: Advances in the molecular biology of AML have confirmed the negative prognostic value of angiogenesis; and uncovered potential molecular targets including VEGF. VEGF stimulation is...