ALBERT

Description: Abstract 4142 Introduction: High dose chemotherapy combined with autologous stem cell transplantation (ASCT) as opposed to conventional chemotherapy improved progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) and is currently the standard of care for newly diagnosed MM patients less than 65 years old. Over the last decade, novel agents such as lenalidomide or bortezomib have dramatically improved MM outcomes with similar response rates as ASCT and the role of upfront ASCT has become more controversial. Therefore the goal of this randomized clinical trial is to determine the role of upfront ASCT in newly diagnosed myeloma patients receiving novel agent lenalidomide and low-dose dexamethasone induction. Methods: Patients aged ≥18 years with newly confirmed, measurable MM in stage 2 and 3 (Salmon Durie) and meeting CRAB criteria were enrolled. Patients were randomized to transplant (Arm A) or to non-transplant (Arm B). Patients in Arm A received 4 cycles of lenalidomide (25mg days 1 – 21) plus low-dose dexamethasone (40mg days 1,8,15,22) followed by ASCT conditioned with 200 mg/m2 melphalan (LD+ASCT); Arm B patients received 8 cycles of lenalidomide plus low-dose dexamethasone (LD alone). Both arms received stem cell collection after 4 cycles of therapy if patients achieved at least a partial remission (PR). Patients with stable disease (SD) or progressive disease (PD) went off study. The primary objective was to compare best response. The secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS) and evaluation of secondary malignancies in both arms. Results: From February 2008 to May 2011, 44 patients with newly diagnosed MM were randomized. The patient characteristics were as follow: median age of the patients was 61.7 years (range 48∼75), 45.5% female and 55.5% male patients, ISS stage I 31%, II 51% and III 18%. 40 patients were eligible for evaluation and 20 patients were randomized to Arm A or Arm B, respectively. The data were analyzed according to latest IMWG response criteria (Blood. 2011 May 5;117(18):4691–5). In an intention to treat analysis, patients in Arm A (LD + ASCT), achieved a 100% Overall Response Rate (ORR) with 40% PR (n=8) and 60% Very Good Partial Response (VGPR) (n=12). In Arm B (LD only) the ORR was 75% (n=15), including 15% CR (n=3), 35% VGPR (n=7), 25% PR (n=5), 20% SD (n=4) and 5% PD (n=1). The ORR was significantly superior in the LD+ASCT group compared to LD alone (p=0.047). After a median follow-up of 25.3 months, 17 patients have PD (8 in LD+ASCT and 9 in LD alone), 6 have died (1 in LD+ASCT and 5 in LD alone). DOR, PFS and OS were not significantly different in both groups. OS showed a trend to be superior in patients treated with LD+ASCT (p=0.08). (Table 1). One patient in the LD+ASCT arm developed MDS 13 months after start of therapy. Conclusion: Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed MM patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR. There was no difference in terms of DOR or PFS with a trend of superior OS in the LD+ASCT group. The study requires careful interpretation based on the low patient number and relatively short follow up, but supports the continued role of upfront consolidative ASCT in newly diagnosed MM patients. The incidence of secondary malignancy was low with the development of 1 MDS. Updated data on response and overall survival will be available at the time of presentation. Disclosures: Roodman: Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Raptis:Millennium: Speakers Bureau; Celgene Corp: Speakers Bureau; Eisai: Speakers Bureau. Lentzsch:Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria.

Description: Assessment of IgH somatic hypermutation status has been shown to be a valuable indicator for judging the prognosis of patients with chronic lymphocytic leukemia (CLL). Our laboratory has developed a streamlined method to improve the rate of successful evaluation of IgH mutation status. Six individual PCR reactions are first performed using random hexamer-generated cDNA as template. These reactions have identical reaction parameters, use a common JH reverse primer and one of six VH class-specific forward primers within Framework 1. PCR products are separated on acrylamide or MetaPhor® agarose gels following formamide denaturation. In almost all cases, a single homoduplex band is resolved indicating a class-specific clonal product. The homoduplex band is excised from the gel, eluted and directly sequenced. Mutation analysis is performed using the NCBI Ig BLAST program with percent identity determined for the region from the beginning of CDR1 to the end of Framework 3. To date, less than 10% of cases analyzed have not yielded a clearcut clonal PCR product using this approach

Description: The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin–dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human THpopulations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell–attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small “effector” (CLA+/CCR4+/CD27−/CCR7−) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing THcompartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized “effector” cutaneous TH cells to and/or within epidermal microenvironments.

Description: 1. The effect of transfusion polycythemia upon bone marrow activity and erythrocyte survival has been studied in 4 normal young adult males. 2. Plasma volumes did not change significantly throughout the period of study. 3. Total red cell masses increased to the "expected" levels, i.e., to the total of the subjects’ cells plus the transfused cells immediately after the transfusions. Thereafter these fell progressively, reaching the control levels in about forty days. 4. Survival of the infused cells was normal. 5. The subjects’ own red cell masses fell progressively at first. This was due to decreased erythropoiesis rather than to increased destruction. This is indicated by (a) no consistent significant elevation in hemolytic indexes; (b) change of the myeloid-erythroid ratio from normal values of 4 to 7:1 to about 20:1 two weeks post-infusion; (c) consistent decrease in circulating reticulocytes. 6. The depression of erythropoiesis was directly related to the quantity of red cells infused; almost complete cessation of red cell synthesis followed an increase of the red cell mass by forty per cent. 7. The depression of erythropoiesis was only temporary. As soon as the total circulating red cell mass returned to the pre-injection level, erythropoiesis proceeded at a normal rate. 8. No consistent changes in the circulating white blood cells, totals and differentials were noted. 9. Mild abnormalities in some liver functions were observed. Whether these should be attributed to the effects of the transfusions directly, or to the mild febrile responses experienced by the subjects shortly after the infusions cannot be stated with certainty at present.

Description: Introduction: Immune thrombocytopenia (ITP) is an autoimmune phenomenon causing increased destruction and insufficient platelet production. ITP can be a healthcare burden due to prolonged treatment (medical and sometimes surgical = splenectomy) required to prevent the relapse and frequent hospitalizations for management of complications such as epistaxis, gastrointestinal bleeding (GIB) or intracranial hemorrhage (ICH). In addition, septicemia and coagulation disorders can occur related to therapy. In this study we analyzed demographics among inpatient admissions with ITP and the variation of length of stay (LOS) and mortality with different complications. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a primary or secondary diagnosis of ITP and age 〉18 years. We performed descriptive statistics to characterize the cohort in terms of personal demographic factors (age, race, sex, insurance type, community level income level), hospital characteristics (size, region, teaching status, and urban or rural location). The cohort was classified on based on splenectomy status using procedure diagnosis code. The cohort was further analyzed for complications such as coagulation disorders, GIB, ICH, septicemia and epistaxis using their principal diagnosis. Furthermore, we also looked at the variation in LOS and mortality among them. Univariate and multivariate regression analysis were performed to determine statistical significance. All analyses applied the HCUP-NIS weights. Results: There were 11,535 patients in the cohort. Most were white (64.4%), females (57.95%), and aged 〈 60 years (55.6%). A significant proportion were covered by Medicare (41.33%). Most care was delivered in large hospitals (55.17%), that were disproportionately urban (94.4%) or teaching (70.61%) institutions. The greatest segment of patients were in the South Atlantic region (20.8%). Epistaxis occurred in 15.3% of patients, GIB in 3.12%, ICH in 0.41%, and septicemia in 0.99%. The mean LOS was 4.73 days (95% CI 4.49 to 4.97). Mean LOS was highest in patients with septicemia (12.3 days), followed by GIB (8.98 days) and ICH (7.99 days), and epistaxis and coagulation disorders (6 days each). LOS was significantly shorter in patients who had undergone splenectomy (AMD -10.67 95% CI-18.32 to -3.03), and longer with septicemia (AMD 9.06 95% CI 1.84 to 16.27). Compared to Medicare, other insurances statuses had shower LOS: uninsured (AMD -6.60 95% CI -10.76 to -1.39), Medicaid (AMD -3.57 95% CI -7.07 to -0.086), and private (AMD -2.67 95% CI -5.39 to 0.037). Risk of death was much higher with GIB (OR 227 95% CI 7.63 to 6757.48, p=0.002) and ICH (OR 100.88 95% CI 10.27 to 990.91, p

Description: Introduction: Hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) is performed to treat hematologic malignancies such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), lymphomas (HL and NHL) and hemophagocytic lymphohistiocytosis (HLH). Inpatient data on the characteristics of patients receiving BMT, the distribution of BMT among the above mentioned hematological cancers and their outcomes is lacking. This study analyzes patient and hospital characteristics of patients undergoing BMT, in addition the study describes resource utilization and outcomes of BMT among various hematological cancers. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a procedure diagnosis of BMT and a medical diagnosis of acute or chronic leukemia (ALL, AML, CLL, CML), lymphoma (HL and NHL), MM, MDS or HLH. HSCT or BMT includes both Allogeneic and Autologous Stem Cell Transplant however we did not differentiate one from the other since BMT in MM is almost universally auto stem cell transplantation. We performed descriptive statistics to characterize the cohort in terms of personal demographic factors (age, race, sex, insurance type, community level income level), indication for HSCT, hospital characteristics (size, region, teaching status, and urban or rural location), and timing of admission (weekend or weekday). We performed univariate analyses using these variables to determine the associations with LOS and mortality. All analyses apply the HCUP-NIS weights. Results: The cohort comprised of 18,275 patients who underwent HSCT. Most patients were male (59.1%), white (70.4%), aged 51-70 years (53.9%), and covered by private insurance (57.0%). Nearly a third (31.3%) lived in communities with the highest quartile of household incomes. The most common diagnosis associated with HSCT was MM (27.6%), followed by AML (15.6%). Most HSCT was performed at large hospitals (74.5%); only 0.1% were performed in rural and 1.1% at non-teaching hospitals. Average length of stay (ALOS) was 25.54 days (95% CI 24.19 to 26.89) and the mean total charges (per hospitalization) were $346,555 (95% CI $310,465 to $382,645) and net charge was $6.33 billion. Several factors were associated with lower ALOS: age (AMD -0.31, 95% CI -0.37 to -0.24), Charlson index (AMD -0.85, 95% CI -1.60 to -0.12), private insurance coverage (AMD -3.65, 95% CI -5.25 to -2.067) and self pay status (AMD -13.56, 95%CI -17.13 to -10.00). Urban (AMD 6.74, 95% CI 1.01 to 12.48), and teaching hospitals (AMD 8.31 95% CI 2.88 to 13.72) had longer ALOS. Only Hispanic race (OR 0.23 95% CI 0.068 to 0.77) and Charlson index (OR 1.2 95% CI 1.04 to 1.39) were associated with mortality. Multivariate analysis did not show any significant associations of mortality with age, race, geographic region, hospital size, median household income, type of insurance, timing of admission, or teaching or location status of hospitals. Discussion: MM accounted for the most significant portion of HSCT in 2014, although its incidence is lower than that for leukemia and lymphoma. This may partly be because autologous stem cell transplantation (ASCT) after high dose chemotherapy is the mainstay of MM treatment. In contrast to other hematological malignancies, some MM patients may also undergo tandem transplantation. Most HSCT recipients were covered under private insurance, and a significant proportion of them came from communities with the highest quartile of median household incomes. This suggests that socioeconomic status influences access to HSCT therapy, likely related to out of pocket costs. In addition, social determinants of health including health literacy, access to health care may play a role. Surprisingly, ALOS decreased with increasing age and Charlson comorbidity index. Reasons are unclear but may be related to increased or earlier mortality. Additional studies could help to elucidate this relationship. Figure. Figure. Disclosures Bussel: Rigel: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Momenta: Consultancy; Uptodate: Honoraria; Protalex: Consultancy; Amgen Inc.: Consultancy, Research Funding; Prophylix: Consultancy, Research Funding. Marks:Odonate: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Equity Ownership; Lilly: Membership on an entity's Board of Directors or advisory committees; Heron: Membership on an entity's Board of Directors or advisory committees; UPMC: Employment.

Description: Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease in which impaired natural killer and cytotoxic T-cell function results in excessive immune activation. It is predominantly seen in children; most of the available data comes from the pediatric population so it cannot be generalized to adult HLH. Treatment of HLH usually involves either treating the underlying cause in the secondary form (i.e. malignancy with chemotherapy, rheumatologic with immune suppression) or chemotherapy and stem cell transplantation for primary, familial etiology, multiple courses of intensive chemotherapy, with stem cell transplantation for relapse and familial disease. Recently, increasing adult HLH cases have been reported. The goal of this study is to describe the association between patient factors, geography, hospital resource utilization, and mortality among adult HLH patients. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2012, 2013 and 2014 Databases (HCUP-NIS). Patients were included in the study if they had a principal diagnosis of HLH and were older than 18 years. We used descriptive statistics to characterize the cohort in terms of personal demographic factors (age, race, sex, insurance type, community-level income level), hospital characteristics (size, region, teaching status, and urban or rural location), and admission timing (weekend or weekday). We performed univariate and multivariate regression to analyze the association of the following factors with length of stay and mortality: age, sex, Charlson index, hospital region (Northeast NE, Midwest MW, South, West), income, insurance, hospital size, weekend versus weekday, hospital location (rural versus urban), teaching status. All analyses applied the HCUP-NIS weights. Results: The cohort comprised 760 patients, the majority of whom were male (57.9%), aged 21-30 years (26.3%), white (56.3%), and treated in large (78.9%) and/or teaching (92.1%) hospitals, third quartile for median household income (30.4%), covered by private insurance (43.4%), and treated in the southern US (32.2%). Per hospitalization, the average total hospital charges were $210,526 (95% CI $176,251 to $244,801) and the average length of stay (ALOS) was 18 days (95% CI 16 to 20). On multivariate analysis, ALOS was significantly longer with patients at teaching hospitals (AMD 5.10 95% CI 0.57 to 9.64, p=0.03) or with self-pay status (AMD 29.05 95% CI 21.62 to 36.48, p

Description: Introduction: Multiple myeloma (MM) requires hospitalization for chemotherapy, stem cell transplantation, and for disease or treatment-related complications. Although there is data regarding overall incidence and mortality of MM, less is known about the patterns of hospital utilization and inpatient mortality. The purpose of this study was to describe the characteristics of patients hospitalized in 2014 for a primary diagnosis of MM, and factors associated with length of stay (LOS) and inpatient mortality. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a principal diagnosis of MM and were aged 18 years or older. We used descriptive statistics to characterize the cohort in terms of personal demographic factors (i.e., age, race, sex, insurance type, community-level income level), hospital characteristics (i.e., size, region, teaching status, and urban or rural location), and admission timing (i.e., weekend or weekday). We performed univariate analyses and multivariate analysis using these variables to determine the associations with LOS and mortality. All analyses apply the HCUP-NIS weights. Results: The cohort comprised 16,890 patients. Most were white (63.7%), males (54.7%), and aged 61 years or older (64.8%). Nearly half (49.2%) were insured by Medicare. Hospitalizations were uniformly distributed across socioeconomic groups based on median household income by zip code. Care was delivered most often in large hospitals (69%) and urban teaching hospitals (81.5%). The greatest proportion of patients received care in the South (37.2%) and the least in the West (15.7%). Mean hospital charge was $ 113272 (95% CI $104651 to $121893) and net total hospital charge was $1.9 billion. The mean LOS was 11.4 days (95% CI 10.87 to 12.015). On multivariate analysis LOS was longer with increased Charlson index (AMD 0.77, 95% CI 0.56 to 0.98, p

Description: Introduction: Cancer patients tend to have a higher incidence of venous thromboembolism (VTE) - pulmonary embolism (PE) and deep venous thrombosis (DVT). There is conflicting data in the literature about the incidence of VTE in solid tumors versus hematological cancers. The purpose of this study was to analyze the prevalence of PE, DVT, and VTE in hospitalized patients with solid and hematologic malignancies using the National Inpatient Sample database. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a principal diagnosis of DVT, PE, or both (VTE); primary or secondary diagnosis of solid tumors or hematological malignancy; and age 18 years or older. We performed univariate and multivariate regression to analyze the association of PE, DVT, and VTE with solid versus hematologic cancers. We performed univariate and multivariate regression to determine their statistical significance. We also performed univariate analysis for tumor type and saddle PE and upper extremity DVT. All analyses applied the HCUP-NIS weights. Results: We identified 27,410 patients with isolated DVT; 41,645 with isolated PE; and 69,055 with both DVT and PE (VTE). On multivariate analysis, hematologic malignancy had lower odds of DVT (OR 0.82, 95% CI 0.75-0.89), isolated PE (OR 0.65, 95% CI 0.60 - 0.71) and VTE (OR 0.72, 95% CI 0.67-0.76). Female sex and Charlson index were associated with modest increased odds of DVT, PE and VTE (OR

Description: Introduction: Both acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) require hospitalization for intensive chemotherapy, stem cell transplantation, and disease or treatment-related complications. There is a dearth of evidence in prediction of inpatient resource utilization and hospital outcomes among patients with these conditions. The goal of this study is to identify predictors of average length of stay in the hospital (ALOS) and inpatient mortality in adult ALL and AML patients. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a principal diagnosis of ALL or AML and age 18 years or older. We used descriptive statistics to characterize the cohort in terms of personal demographic factors (age, race, sex, insurance type, community income level), hospital characteristics (size, geographical region, teaching status, and urban or rural location), and admission timing (weekend or weekday). We performed univariate and multivariate regression to analyze the association of these factors with mortality and ALOS. All analyses apply the HCUP-NIS weights. Results: The ALL cohort included 5,550 admissions. Most ALL patients were white (65%) males (60%), and approximately half were age 50 years or younger. The AML cohort included 18,930 admissions. Most AML patients were white (74%) males (54%), aged 60 years or older (59%). Nearly all (95%) of ALL patients had insurance coverage, either private (40%), Medicare (25.9%), Medicaid (25%), or another type (5%). In contrast, most AML patients had Medicare (46%), followed by private insurance (36%), Medicaid (11.0%), other insurance (3.8%) or no insurance (2.8%). Care for both cohorts occurred most often in large, urban, and teaching hospitals. While Charlson index was the only statistically significant predictor of mortality in the ALL cohort (AMD 1.34, 95% CI 1.11 to 1.63, p=0.002), age (OR 1.02; 95% CI 1.014 - 1.03), Charlson index (OR 1.24; 95% CI 1.16 - 1.34) and other type of insurance were associated with increased mortality for AML. ALOS was similar for both cohorts: ALL 18.5 days and AML 18.9 days. For ALL, multivariate analysis showed Charlson index (AMD 1.53, 95% CI 0.32 - 2.74, p=0.013), and hospital type (urban AMD 5.73; 95% CI 2.73 to 8.73, p