bluuebunny/crossref_metadata_2025 huggingface dataset:
Weight changes in breast cancer survivors who received adjuvant antiestrogen therapy
Authors: Harris B. M. , Broxson A. C. , Anderson L. A. , Engelbrink J. G. , Zalewski M. A. , Broglio K. R. , Hortobagyi G. N. , Green M. C.
Published: August 2020

6588

Background: Antiestrogen therapy has dramatically improved breast cancer survival rates but weight gain may be problematic. Studies evaluating antiestrogen therapy-related weight gain have yielded mixed results. Our primary objective was to evaluate weight changes in female breast cancer survivors (BCS) who received adjuvant anti-estrogen therapy for stage 0-III breast cancer. Methods: A retrospective chart review was conducted to evaluate weight changes in female chemo naive BCS receiving anti-estrogen therapy. Weights at initiation of hormonal therapy and at 6, 12, 24, and 36 months of follow-up were recorded. Median weight changes were calculated and were compared with Wilcoxon's signed rank test or the Kurskall-Wallis test. Results: A total of 622 women were included. The majority were white (77%), had stage I disease (78%), and were postmenopausal (82%). The median age at diagnosis was 59 years (range, 26–87). Median weight at initiation of hormonal therapy among premenopausal women was 65 kg (range 45.4–122.9). Median weight gain in this group was 0.4 kg (p = 0.009), 0.7 kg (p = 0.013), 1.9 kg (p = 0.0001), and 2.4 kg (p < 0.0001) at 6, 12, 24, and 36 months respectively. Among post-menopausal women, median weight at initiation of therapy was 71.7 kg (range 41.5–152.0) and median weight gain was 0.5 kg (p < 0.0001), 1 kg (p < 0.0001), 0.85 kg (p = 0.001), and 0.85 kg (p = 0.004) at 6, 12, 24, and 36 months respectively. Premenopausal patients had significantly more weight gain at 24 (p = 0.041) and 36 months (p = 0.005), as compared to postmenopausal patients. Among premenopausal women, 110/111 were treated with tamoxifen. Among post-menopausal women (n = 510), hormonal therapy was as follows: unknown n = 28 patients, tamoxifen n = 312, and AI n = 170. Overall, BCS treated with tamoxifen vs an AI had significantly more weight gain at 24 (p = 0.003) and 36 months (p = 0.009). Conclusions: Premenopausal patients are at higher risk for weight gain than postmenopausal patients. Further prospective research is warranted examining weight gain as a long-term side effect of anti-estrogen therapy in BCS.

No significant financial relationships to disclose.
Nab-paclitaxel weekly or q3w compared to docetaxel q3w as first-line therapy in patients with metastatic breast cancer: An economic analysis of a prospective randomized trial
Authors: Dranitsaris G. , Coleman R. , Gradishar W.
Published: August 2020

6592

Background: In patients with MBC, the current practice is first-line chemotherapy often with a taxane such as docetaxel. However, docetaxel is associated with dose-limiting toxicities. A nanoparticle albumin-bound (nab) formulation of paclitaxel was recently developed to overcome the safety drawbacks of docetaxel and to provide additional efficacy. A randomized phase II trial comparing nab-paclitaxel 100 or 150 mg/m2 weekly 3 out of 4 and nab-paclitaxel 300 mg/m2 q3w to docetaxel 100 mg/m2 q3w reported improved progression-free survival and reduced toxicity with the former regimens (Gradishar, 2008). To measure the economic value of the nab-paclitaxel regimens, an economic analysis from the perspective of the United Kingdom (UK) was conducted. Methods: The current study extracted data captured during the randomized trial. Resource utilization data contained within the database were converted into UK cost estimates. This consisted of costs for chemotherapy, drug delivery, patient monitoring, supportive care drugs, and hospitalization due to toxicity. Multivariate regression analysis was then conducted to compare the total cost of therapy between the four regimens. Results: Growth factor use, hospital days for side effects management, and toxicity-induced protocol discontinuations were higher in the docetaxel group. When all of the cost components were combined for the entire population (n = 300), patients in the nab-paclitaxel 100 mg/m2 weekly and 300 mg/m2 q3w groups had comparable costs to the docetaxel control (£15,396 vs. £15,809 vs. £12,923; p = NS). The nab-paclitaxel 150 mg/m2 weekly arm had significantly higher overall costs of £27,222 but was associated with a significant improvement in progression-free survival relative to docetaxel. As alternatives to docetaxel, the incremental cost per progression-free year gained with nab-paclitaxel 100, 150 mg/m2 weekly and 300 mg/m2 q3w were £5,600, £31,800, and £9,900 respectively. Conclusions: Given its more favorable safety profile, superior efficacy, and reasonable economic impact, nab-paclitaxel (weekly or q3w) can be a preferred option over docetaxel as first-line chemotherapy in MBC.

[Table: see text]
Is race a prognosticator for survival in metastatic non-small cell lung cancer?
Authors: Berz D. , Birnbaum A.
Published: August 2020

6610

Background: Available cancer statistics for non-small cell lung cancer (NSCLC) in the US relate mainly to Caucasians and African Americans. NSCLC also represents a major health concern in other US American sub-populations. This study describes ethnic patterns of survival in metastatic NSCLC in eight different racial/ethnic groups. Methods: We analyzed the SEER (surveillance, epidemiology, and end results) program database for cancer specific survival rates in stage IV NSCLC patients who were diagnosed between 1991 and 2004 in the SEER catchment geographic areas. The primary exposure of interest was race. The eight different race groups were non-Hispanic whites, Hispanics, African Americans, American Indians/Alaskan natives, Filipinos, Japanese, Chinese, Hawaiians, and other. The later group consisted mainly of a mix of different Asian subpopulations. We performed uni- and multivariate non-parametrical and parametrical survival analysis and developed a final cox-proportional hazard model controlling for marital status, age at diagnosis, year of diagnosis, gender and histologic type and grade. We tested the proportional hazard assumptions with graphical and modeling methods Results: We identified 39,784 eligible patients. When compared to non-Hispanic whites the risk of death from lung cancer was highest amongst American Indians/Alaskan Natives hazard ratio 1.33(95% CI 1.09–1.62, p = 0.004). For patients with Chinese HR 0.84 (95% CI 0.77–0.91) and Filipino HR 0.80 (95% CI 0.73–0.88) ethnicity the risk of death from lung cancer was significantly lower when compared with non-Hispanic whites. Hispanics HR 1.00 (95% CI 0.94–1.07) and Blacks HR 1.00 (95% CI 0.97–1.04) had about equal hazards of death from stage IV NSCLC as whites. In patients of Japanese and Hawaiian origin a trend towards a lower hazard with HR 0.99(95% CI 0.90–1.08) and HR 0.97(95% CI 0.85–1.09) respectively was identified without reaching statistical significance. Conclusions: Significant racial disparities in the outcome in metastatic NSCLC can be observed in the US. The indigenous populations of the Western hemisphere have the worst outcome and the previously proposed worse outcome of African Americans with NSCLC when compared to non-Hispanic whites could not be confirmed in our study.

No significant financial relationships to disclose.
The impact of randomized trial results and altered regulatory policies on ESA use, transfusions, and thrombosis: A longitudinal analysis over a 3-year period of resource utilization data from a large comprehensive oncology program
Authors: Shapira I. , Raftopoulos H. , Gralla R. J. , Pelc K. , Gleason K.
Published: August 2020

6611

Background: Recent randomized trials and meta-analyses demonstrated unexpected findings with ESA use with chemotherapy. Results revealed an overall increase in thrombosis rates with the use of ESAs as well as decrements in survival in some malignancies, particularly with breast and head and neck cancers (Bohlius, JNCI, 2006; Raftopoulos, Proc ASCO, 2008; Bennett, JAMA 2008). Benefits with ESA use have resulted in an average 1–1.5g/dl rise in hemoglobin. The impact on quality of life and fatigue remains controversial. Toxicity issues have led to restricted labeling by the FDA and reimbursement decisions by the Centers for Medicare and Medicaid Services (CMS). Despite these risks associated with the use of ESAs, concerns regarding increased use of transfusions remain prominent. A longitudinal study to assess the impact of these ESA policies was conducted to assess the demand on transfusion services and ESA use over time. Methods: Our center comprises a large comprehensive combined hematology and oncology program and has a non- restrictive transfusion policy, allowing physician discretion and the capacity to accommodate all out-patient transfusions. We analyzed ESA use over the 3 year period, 2006–2008. 2006 functioned as our baseline; 2007 was the year of initial FDA and CMS changes; 2008 allowed us to see if practice changes would persist. Results: We present in the table below, our data on ESA use and transfusion resource utilization. Conclusions: With over 60,000 patient visits during 3 years, longitudinal assessment reveals a continued, marked decrease in ESA use. Despite liberal transfusion policies, there has been little effect on transfusion rates. Increases in transfusions are commensurate with a rise in patient visit volume. We are now evaluating whether this marked decrease in ESA use translates into decreased thrombosis rates over this 3-year period at our cancer center.

[Table: see text]

No significant financial relationships to disclose.
Impact of direct physician-to-physician contact on accelerating oncology clinical trial accrual
Authors: Eckardt J. R. , Ku N. , DeMaggio A. , Reese M. , Levonyak M. , Jain V.
Published: August 2020

6613

Background: The development of more effective oncology agents is critically dependent on the completion of clinical trials; currently, >4000 oncology trials listed in www.clinicaltrials.gov are accruing pts in the US. Unfortunately, only 3–5% of new cancer pts participate in clinical trials and most trials do not meet their projected accrual timelines. Barriers to pt accrual include physician awareness & attitudes, access to protocols, administrative burdens to conduct clinical trials, cost to physicians and pts, and pt concerns about participation in research trials. To overcome at least some of these barriers, we investigated a strategy to improve clinical trial accrual that optimizes trial placement and awareness through a direct physician to physician intervention. Methods: For each site, a customized enrollment plan is established after initial assessment of interest and accrual potential. Implementation of the enrollment plan includes clinical communications and medical support delivered through direct physician to physician interactions. From Feb 2008 to December 2008, we implemented this strategy to increase accrual to 5 oncology trials (2 placebo controlled randomized trials and 3 phase II trials in breast cancer, non-Hodgkin's lymphoma and soft tissue sarcoma). Results: The implementation of direct physician to physician intervention resulted in a measurable improvement of between 50 - 300% in the monthly accrual to each of these 5 trials. Despite being significantly behind projections, 2 of the trials have now completed accrual on schedule. In the ongoing phase III study, accrual has improved from an average of 3.8 pts/mo to 13.5 pts/mo. Conclusions: The use of our current model of optimizing trial placement and awareness through a direct physician to physician intervention has been successful in significantly accelerating clinical trial accrual in 5/5 trials initiated to date.

[Table: see text]

[Table: see text]
Is squamous cell histology an adverse prognosticator for survival of malignancies of the upper urinary tract?
Authors: Rizack T. , Mega A. , Berz D.
Published: August 2020

6617

Background: Carcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies. Methods: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 0.42 (95% CI 0.36–0.47) for TCC when compared to SCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (p = 0.84) and for patients with clear lymph nodes (p = 0.92). Conclusions: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.

No significant financial relationships to disclose.
Psychosocial impact of cancer-related symptoms among patients with lung cancer
Authors: Walker M. , Peltz G. , Houts A. , Pohl G. , Schwartzberg L. , Stepanski E. , Marciniak M.
Published: August 2020

6621

Background: Patients with lung cancer may experience adverse physical symptoms due to cancer, cancer treatment, or comorbid medical conditions. These cancer-related symptoms (CRS) may be associated with functional impairment (FI), and may affect psychosocial functioning. Methods: We conducted a retrospective analysis of self reported symptom burden with the 38-item Patient Care Monitor survey (PCM), collected as part of routine clinical care in 1,384 lung cancer patients identified by ICD-9 codes at 8 community oncology practices in the US. Structural equation models were built among 672 randomly selected patients to examine the relationships of CRS and of FI on psychosocial symptoms and to determine whether FI mediates the effect of CRS. Results: Patients were 47.7% female, with mean age of 66 years (23–91), 65% Caucasian, 16% African American, 19% other/unknown race. Stage of disease was 19% stage IV, 22% stage I-III, and 59% unspecified. Histological type was 36% adenocarcinoma, 18% squamous cell, 37% unspecified, and 9% other. The most common comorbidities were anemia, other malignancies, and respiratory disease. Depressive disorder was recorded for < 5% of patients. Surveys were collected between 2005 and 2008, ranging up to 5 years after the start of treatment (median 79 days after start of chemotherapy). Half (50.4%) of surveys were collected while the patient was in active treatment. Model findings supported a 1 factor measurement model of 19 CRS items, and a 1 factor measurement model of 8 FI items. Findings supported a 2 factor model of 11 psychosocial items, with resulting factors reflecting acute distress and despair. CRS were less severe longer after the start of chemotherapy, and not significantly worse during vs. off chemotherapy. More severe CRS significantly predicted more severe acute distress and despair, and more severe FI. In contrast to expectations and some previous research, FI was not significantly related to acute distress and despair, and did not mediate the effect of CRS on acutedistress and despair. Conclusions: Cancer related symptoms are associated with FI and with psychosocial outcomes in lung cancer patients. However, FI does not appear significantly related to psychosocial outcomes.

[Table: see text]
Enrollment of lung cancer patients on clinical trials at an NCI comprehensive cancer center
Authors: Keedy V. L. , Horn L. , Hayes A. , Spencer B. , Garcia G. , Campbell N. , Sandler A. , Carbone D. , Johnson D. H.
Published: August 2020

6633

Background: Enrollment of cancer patients (pt) in clinical trials is considered essential in order to improve cancer care. However, cancer clinical trials participation remains low. Understanding barriers to pt enrollment is necessary to overcome this problem. Previous reports have identified pt age, race, and ethnicity, disease stage, performance status (PS) and relationship with their health care provider as factors that can influence the enrollment of pts in clinical trials. Methods: We conducted a retrospective review of the charts of all lung cancer pts seen in the Thoracic Oncology Clinic at Vanderbilt Ingram Cancer Center between November 2005 and November 2008. A total of 1075 lung cancer pts were seen. Results: 577 charts (of a planned 1075) have been audited to date. Pt demographics: median age = 64 yrs; male = 54%; Caucasian = 92%, African American = 4%, and Asian = 1%; NSCLC = 80%, SCLC = 17%. Male pts were more likely than females to be eligible for a clinical trial (p = 0.056). A study protocol was available for 57% of pts; 52% of pts proved eligible; 36% were entered into a study (11% total population). Significantly more protocols were available for NSCLC pts compared to pts with SCLC (p ≤ 0.001); there was also a non-significant trend towards higher enrollment of eligible NSCLC pts. There was no difference in eligibility between ethnicity; the percentage of eligible pts enrolling on trials was similar between Caucasian & African American pts (46% and 43%); no Asian pts were enrolled. The most common reasons for not enrolling included a preference for treatment closer to home (29%), patient refusal (19%), PS (19%), and co-morbidities (17%). The distance pts traveled was inversely correlated with likelihood of study participation. Conclusions: A total of 11% of lung cancer pt evaluated in our Thoracic Oncology Clinic were enrolled in clinical trials. Our data suggest additional strategies are needed to attract minority groups, increase enrollment of women and pts with comorbidities and poor PS. Travel distances influence pt willingness to participate in clinical trials. Strategies are needed to overcome this factor.

No significant financial relationships to disclose.
A randomized trial of anthracycline dose intensification during induction of younger patients with acute myeloid leukemia: Results of Eastern Cooperative Oncology Group study E1900
Authors: Fernandez H. F. , Sun Z. , Litzow M. R. , Luger S. M. , Paietta E. M. , Dewald G. , Ketterling R. P. , Rowe J. M. , Lazarus H. M. , Tallman M. S.
Published: August 2020

7003

Background: In younger adults with newly diagnosed acute myeloid leukemia (AML), anthracycline dose intensification during induction may improve complete remission (CR) rates; however, an improvement in overall survival (OS) in a randomized trial has not been demonstrated. This unresolved issue led the ECOG to compare standard dose (SDD) to high-dose daunorubicin (HDD) in induction. Methods: Adult patients with previously untreated AML were randomized to receive either SDD (45 mg/m2/d) or HDD (90 mg/m2/d) each for 3days combined with standard-dose cytarabine (100 mg/m2/d) for 7 days by continuous intravenous infusion. Those achieving a CR were allocated to allogeneic hematopoietic stem cell transplantation (HSCT) or high-dose cytarabine (with or without a single dose of gemtuzumab ozogamicin) prior to autologous HSCT. Intravenous busulfan and cyclophosphamide was the preparative regimen for both allogeneic and autologous HSCT. The primary end point of this study was OS from the time of induction randomization. Results: 633 patients, age 18 to 60 (median 48) years, were entered in this study. There were no differences in patient demographics or disease characteristics between the two groups at presentation. In an intention-to-treat analysis, HDD resulted in a significantly higher CR rate (63.3% vs. 47.7%, p = 0.0003) than SDD. Induction deaths were similar between the two groups (5.4 vs. 5.0%, p = ns). 334 (52.8%) patients entered the consolidation phase. 57.4% of HDD and 48.1% of the SDD patients, received consolidation therapy on study, and 28.7% and 23.1% proceeded to HSCT respectively. Median OS was superior for the HDD (23.7 months) over the SDD (15.1 months) group (p = 0.005). In subgroup analysis, patients with favorable or intermediate-risk cytogenetics or age <55 years benefited from the HDD. Conclusions: We demonstrate for the first time in a prospective randomized trial that intensifying induction therapy through a higher daily anthracycline dose, in the setting of identical intensive consolidation therapy, results in a higher CR rate as well as prolonged OS. In younger AML patients a higher dose of anthracycline in induction should be considered the new standard of care.

No significant financial relationships to disclose.
Phase II study of vorinostat (V) in combination with idarubicin and high-dose cytarabine (IA) as front-line therapy in patients (pts) with high-risk myelodyplsatic syndrome (MDS) or acute myeloid leukemia (AML)
Authors: Jabbour E. , Faderl S. , Ravandi F. , Konopleva M. , Verstovsek S. , Cortes J. , Wierda W. , Newsome W. M. , Yang H. , Kantarjian H. , Garcia-Manero G.
Published: August 2020

7004

Background: Standard induction therapy for pts with AML has not changed over the last 2 decades nor has the outcome of these pts. We demonstrated in vitro and ex vivo that the combination of an histone deacetylase inhibitor with anthraycline is synergistic (Blood 2006;108:1174); an effect that could be mediated by activation of DNA damage/repair pathways, and found that such combination is safe in phase 1 trial (Blood 2007;110:1842). We designed a phase II study of V with IA as front-line therapy for MDS/AML. Methods: Pts with untreated int-2/high-risk MDS or AML ages 15–65 with adequate liver and renal functions and PS, and EF ≥ 50% were eligible. Pts with CBF were excluded. Initial dose of V was 500 mg orally TID for 3 days followed on day 4 by IA (I:12 mg/m2/dx3; A:1.5g/m2/dx4 over 24 hrs). After induction and if in CR, pt can receive 5 cycles of consolidation with V at the same dose and IA (I:8 mg/m2/dx2; A:0.75g/m2/dx3 over 24 hours) followed by 1 year of maintenance with V. The study was powered to demonstrate improvement in PFS at 7 months and acceptable toxicity. Prior to formal initiation of the phase II, the study had a “run-in” phase to confirm the safety of the triple combination. Correlative studies include analysis of DNA repair/damage pathways. Results: 22 pts have been registered. 3 pts with relapsed/refractory AML were treated in the run-in phase. No excess toxicity was observed; 2 achieved CR and 1 CRp. Following these, 19 pts were enrolled on the phase 2 portion. 17 pts were evaluable. Median age was 49 years. Median WBC at presentation was 12.75 x 109/L. Cytogenetic analysis were abnormal in 12 (71%), complex in 10 (59%). 8 (47%) had secondary disease. 4 (23%) were Flt-3 positive. No unexpected grade 3/4 toxicities have been observed. The CR rate was 82%. 1 pt acheived a marrow CR and 2 pts died during induction. CR were universally associated with CG response. All Flt-3+ pts achieved a CR. Only 2 pts (14%) have relapsed (4 and 5 months). The median PFS has not been reached. Conclusions: The combination of IA and V is safe and active in AML/MDS. No stopping rule has been met. Results will be compared with those of a parallel IA study at MDACC. Correlative analysis are ongoing.

[Table: see text]
Randomized phase II trial of the nucleolin targeting aptamer AS1411 combined with high-dose cytarabine in relapsed/refractory acute myeloid leukemia (AML)
Authors: Stuart R. K. , Stockerl-Goldstein K. , Cooper M. , Devetten M. , Herzig R. , Medeiros B. , Schiller G. , Wei A. , Acton G. , Rizzieri D.
Published: August 2020

7019

Background: Aptamers are small synthetic oligonucleotides that form stable nuclease-resistant 3D structures and bind target proteins with specificity and affinity similar to antibodies. These “chemical antibodies” represent a new class of therapeutics. The AS1411 aptamer binds nucleolin on the surface of cancer cells and induces apoptosis. AS1411 has synergistic effects in combination with cytarabine on AML cell lines in vitro and in vivo. A phase I trial of AS1411 monotherapy in 30 patients with advanced cancer showed objective responses without serious toxicities. Methods: This open-label randomized phase II trial compared AS1411 plus high-dose cytarabine (HiDAC) with HiDAC alone in patients with primary refractory or relapsed AML who had received up to 3 previous lines of chemotherapy. Patients in cohort I were randomized 2:1 to receive AS1411 10 mg/kg/day as continuous IVI on days 1–7 + HiDAC 1.5 g/m2/ twice daily on days 4–7 or HiDAC alone for 4 days. Following safety assessment, a second cohort was randomized in a similar manner, with AS1411 escalated to 40 mg/kg/day. Objectives were comparison of response rates (CR+CRp), safety and tolerability between treatment groups. Results: Accrual has been completed, with 71 patients randomized: 22 to AS1411 10 mg/kg/day + HiDAC (AS1411–10), 26 to AS1411 40 mg/kg/day + HiDAC (AS1411–40) and 23 to HiDAC alone (control). Safety findings are currently available for 44 patients (AS1411–10, 21; AS1411–40, 9; control, 14). The main grade 3/4 toxicities were hematologic, notably febrile neutropenia, neutropenia, and thrombocytopenia; and infections. Safety findings were similar across groups, except that grade 3 hypokalemia was more frequent with AS1411–40. Deaths within 28 days of treatment were: AS1411–10, 1/21; AS1411–40, 1/9; and control, 2/14. Response data are currently available for 39 patients; response rates were: AS1411–10, 16% (3/19); AS1411–40, 14% (1/7); and control, 0% (0/13). Conclusions: Data from this first phase II trial of an aptamer in oncology are encouraging. The combination of AS1411 at 10 or 40 mg/kg/day with HiDAC appears well tolerated and shows promising signs of activity in patients with relapsed/refractory AML.

[Table: see text]
Vancomycin resistant enterococci (VRE) infections in hematopoietic stem cell transplant (HSCT) recipients
Authors: Rosko A. E. , Arfons L. M. , Barr P. M. , Cooper B. W. , Kindwall-Keller T. , Laughlin M. J. , Gerson S. , Creger R. J. , Fu P. , Jacobs M. R. , Lazarus H. M.
Published: August 2020

7036

Background: VRE blood stream infections (BSI) pose significant hazards to HSCT patients. Risk factors predisposing patients for a relatively nonpathogenic organism to become bacteremic include immune suppression, neutropenia, renal failure, antibiotic exposure, indwelling catheters, and VRE colonization. Some studies suggest that a VRE BSI is simply a marker of primary disease severity or an indicator of poor outcome, while other data demonstrate VRE BSI as an independent predictor of mortality. Methods: We performed a retrospective chart analysis of HSCT patient data using the electronic medical record and written charts using a standard data collection tool from February 1994 to October 2008. Vancomycin susceptibility was determined using the Dade Berhing panel. Results: We noted 625 infections in 385 HSCT patients; 26 patients developed 27 VRE infections over the course of 15 years. All isolates were Enterococcus faecium and not polymicrobial. Host characteristics included mean age of 49.5 yrs, all had central venous catheters, and 26 received linezolid treatment. Persistent infection was identified in 11 patients with central access removal in 4. VRE colonization was identified in stool (18 patients) and urine (5 patients) and 4 patients had a prior VSE BSI. 16 patients received vancomycin within 30 days of developing VRE BSI. 21 patients were neutropenic (mean duration15 days). 8 patients were not receiving immunosuppressants during time of bacteremia. Gastrointestinal endoscopy was identified in 6 patients prior to BSI. 16 patients died during the hospitalization. Conclusions: VRE accounted directly or indirectly for 13 of 16 deaths during incident hospitalization. In this population, blood, urine, stool surveillance is warranted to prevent morbidity/mortality related to developing a VRE BSI. Prolonged neutropenia was associated with development of a VRE BSI prophylactic granulocyte transfusion might be useful to prevent BSI. In contrast to prior studies, many patients were not receiving immunosuppressants and did not undergo GI instrumentation. VRE BSI prevention should include identifying patients with urinary or stool colonization, appropriate isolation and early central venous catheter removal if a VRE BSI is identified.

No significant financial relationships to disclose.
Low risk for symptomatic venous thromboembolic events (vte) during cytokine administration for peripheral blood stem cell mobilization
Authors: Naina H. V. , Pruthi R. K. , Litzow M. R. , Ansell S. M. , Dispenzieri A. , Hogan W. J. , Gertz M. A. , Elliott M. A. , Gastineau D. A. , Kumar S. K.
Published: August 2020

7039

Background: Erythropoiesis-stimulating agents are known to increase the risk for VTE events, especially in patients with underlying malignancies. However, there is a paucity of information on other hematopoietic growth factors such as granulocyte colony-stimulating factor (GSCF) granulocyte-macrophage colony stimulating factor (GM-CSF) AMD 3001 and risk for VTE. Methods: Between January 2000 and October 2008, a total of 631 patients underwent peripheral blood stem cell mobilization (PBSCM) using either GCSF, GMCSF, cyclophosphamide, AMD 3100, or with any of the above combination. We included only patients with a diagnosis of AL amyloidosis (AL), multiple myeloma (MM) Hodgkin's lymphoma (HL) and non Hodgkin's lymphoma (NHL). Patients’ demographic details and diagnosis of VTE were collected from electronic medical records. Results: Of the 631 patients who underwent PBSCM the median age of the patients was 57 years (range 17–77). 448 patients (71%) received single agent GCSF, 82 (13%) received combination of GMCSF and cyclophosphamide, 52 (8%) received cyclophosphamide and GCSF, 30 patients received a combination of GMCSF and GCSF, 10 (1.5%) patients received GCSF and AMD 3100. Of the 631 patients, 278 (44%) MM, 209 (33%) NHL, 114 (18%) AL, and 20 (3%) had HL. We found 7 (1.1%) patients with symptomatic VTE occurring between administration of growth factors and stem cell transplant. The median duration from the administration of growth factors to detection of VTE was 5 days (range 1–30). Two AL,3 MM and 2 NHL. Of the 7 patients, 2 patients had pulmonary embolism and 1 patient developed deep vein thrombosis. Two patients with AL developed heparin induced thrombocytopenia (HIT). The remaining 4 patients developed symptomatic catheter related thrombosis. Only 1 patient had past history of VTE. Of the 7 patients, 5 received GCSF alone, 1 received GMCSF, and cyclophosphamide, 1 received GCSF and cyclophosphamide. Of the 4 patients who developed catheter related thrombosis, catheter was removed in 2 patients. None of the patients developed VTE related morality. Conclusions: The risk for symptomatic VTE during PBSCM is low. HIT should be considered as a possible cause for VTE in patients undergoing PBSCM.

No significant financial relationships to disclose.
Outpatient versus inpatient autologous stem cell transplantation for malignant hematologic disorders
Authors: Ghavamzadeh A. , Allahyari A. , Alimoghaddam K. , Karimi A. , Shamshiri A. , Abolhasani R. , Manookian A. , Asadi M. , Khatami F.
Published: August 2020

7042

Background: High-dose chemotherapy with autologous stem cell support is utilized for the treatment of a variety of malignancies including Hodgkin/non-Hodgkins lymphoma and acute leukemias. The aim of this study was to compare the time of engraftment and mortality rate and cost of neutropenic treatment in outpatient versus inpatient autologous stem cell transplantation (SCT). Methods: 9 outpatients (5 HL, 2 NHL, and 2 AML) were compared with 32 inpatients (15 HL, 8 NHL, and 9 AML; for whom the outpatient facilities were not ready) from May 2008 to December 2008. All patients were below 45 yrs; median age for outpatients and inpatients were 26 and 30 years respectively. Also all the patients were in complete remission and without significant organ failure. They received conditioning regimen (CEAM for NHL and HL, busulfan and etoposide for AML) and stem cell infusion in hospital. The day after SCT, outpatient group were discharged and followed by outpatient SCT team, and to be re-hospitalized in case of febrile neutropenia, after sepsis workup and performing chest x-ray, they were received the first dose of antibiotic in hospital and treatment continued in home. Results: For outpatients and inpatients, median time to WBC engraftment was 11 and 12 days (p = 0.03), time to PLT engraftment was 15 and 25 days (p = 0.20), number of transfused single donor PLT was 3 and 4.5 units (p = 0.21), duration of neutropenic fever was 6 and 9 days (p = 0.001), duration of hospitalization (after SCT) 0 and 16 (p < 0.001), respectively. All outpatients are alive and 3 patients from other group died between days +35 and +100 after SCT due to transplantation complications. For inpatient group the cost of drugs, just for neutropenic fever antibiotic therapy was six times than outpatient group. Conclusions: Results show that out-patient autologous SCT in malignant hematologic disorders is feasible and comparable with inpatient protocol. We are waiting for more patients and longer follow-up for future conclusions.

No significant financial relationships to disclose.
Expression of different isoforms of the B-cell mutator activation-induced cytidine deaminase (AID) in BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients
Authors: Lonetti A. , Iacobucci I. , Ferrari A. , Messina M. , Cilloni D. , Soverini S. , Papayannidis C. , Baccarani M. , Foà R. , Martinelli G.
Published: August 2020

7049

Since the activation-induced cytidine deaminase (AID) enzyme can target non-immunoglobulin (Ig) genes and may even act as a genome-wide mutator, we investigated AID expression in BCR-ABL1-positive ALL and in chronic myeloid leukemia (CML) at the time of progression to blast crisis. On the 61 de novo adult BCR-ABL1-positive ALL patients (pts), AID mRNA and protein were detected in 36 (59%); their expression correlated with BCR-ABL1 transcript levels and disappeared after treatment with tyrosine kinase inhibitors at the time of remission. AID expression was also found in lymphoid blast crisis CML (50%), but not in myeloid lineage or in chronic phase CML. Different isoforms of AID were identified: 13/61 (21%) pts expressed the full-length isoform; 19/61 (31%) co-expressed the wild-type and different AID splice variants with deaminase activity (AIDΔE4a, with a 30 bp deletion of exon 4; AIDΔE4, with the exon 4 deletion; AIDins3, with the retention of intron 3–4); 4/61 (7%) expressed the AIDΔE3-E4 isoform without deaminase activity (deletion of exons 2 and 3). To investigate whether AID introduces DNA-single strand breaks, we performed a genome wide analysis by 250K NspI single nucleotide polymorphism (SNP) array. Patients who expressed wild-type AID had a higher number of alterations compared to AID-negative (median copy number alteration of 14 versus 4. respectively, p < 0.03). Recurring copy number abnormalities were identified in genes with an established role in leukemogenesis, such as IKZF1, CDKN2A, CDKN2B, PAX5, MELK, BTG1, and MDS1. Our findings show that BCR-ABL1-positive ALL cells aberrantly express different isoforms of AID that can act as mutator outside the Ig gene loci in promoting genetic instability in leukemia cells. Supported by: European LeukemiaNet, AIL, AIRC, FIRB 2006, Fondazione del Monte di Bologna e Ravenna, Strategico di Ateneo, GIMEMA Onlus.

No significant financial relationships to disclose.
A phase III study exploring various doses of imatinib (IM) or IM in combination for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) patients (pts): Results of an interim analysis of the SPIRIT trial of French CML group
Authors: Nicolini F. E. , Mahon F. X. , Guilhot J. , Buzyn A. , Tulliez M. , Berthou C. , Christian B. , Guyotat D. , Preudhomme C. , Guilhot F.
Published: August 2020

7058

Background: IM 400 mg daily is the front-line treatment of CP CML, but provides only 50% major molecular responses (MMR) at 18 months (Mo). We designed a phase III randomized multicenter open-label prospective trial comparing IM 400 mg/d (n=159) with 3 experimental arms: IM 600 mg/d (n=160), IM 400 mg/d + s/c cytarabine (Ara-C), (20 mg/m2/d, d15–28 of 28-day cycles) (n=158) and IM 400 mg/d + s/c Peg-IFN2a (90 μg/wk) (n=159). Pts were allocated at a 1.1.1.1 ratio, stratified by Sokal risk groups. Molecular assessments were centralized and blinded. An interim analysis of 636 pts was planned based on an IS BCR-ABL/ABL ratio <0.01% (Optimal Molecular Response, OMR) at 1 year (α=0.85%, β=10%). Results: 636 pts were recruited between 9/2003 and 10/2007, median age 51 (18–78) yrs, 62% males, median follow-up for alive pts 36 (12–62) Mo. At 3 Mo, 88% of pts achieved complete hematologic response. Complete cytogenetic response (CCyR), MMR and OMR rates are presented (Table). MMR rates at 6 and 12 Mo were higher for IM-PegIFN as compared to IM-400 (p<10-3). At 18 Mo the cumulative OMR rates were 22% (IM-400), 28% (IM-600), 25% (IM-Ara-c), 43% (IM-PegIFN). Grade 3/4 neutropenia and/or thrombocytopenia occurred during the first year in 8% IM-400, 14% IM-600, 41% IM-Ara-C and 40% IM-PegIFN arms respectively. Grade 3/4 non-hematological toxicities occurred in 19% IM-400 (edemas, muscle cramps), 30% IM-600, 27% IM-Ara-C (diarrhea) and 31% IM-PegIFN pts (skin rashes, asthenia). Within the first 12 Mo, discontinuation of experimental treatment occurred in 8% IM-600, 39% Ara-C and 45% PegIFN pts. Conclusions: Although a significant number of pts reduced or stopped PegIFN within the first year, significant improvements in molecular response rates were observed in the IM-Peg IFN arm and may translate into survival benefit.

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Phase I study results of nanomolecular liposomal annamycin in refractory ALL
Authors: Shepard R. C. , Talluto C. C. , Jacob G.
Published: August 2020

7066

Background: There continues to be no effective second-line therapy for refractory AML or ALL and the cure rate with current therapy has not significantly improved in decades. The first-line therapy for adult AML has remained the same 7 + 3 that it was a generation ago. Annamycin was specifically synthesized to overcome MDR and to have little to no cardiac toxicity when given as a nanomolecular liposomal entity. Methods: We performed a phase I multi-center, open-label, MTD study of nanomolecular liposomal annamycin in patients with refractory ALL. The secondary objective was to study the MDR-1 encoded P-1u70 glycoprotein expression in correlation with CD34 expression and MDR-1 MRP mRNA levels in refractory ALL patients before and after receiving liposomal annamycin. Results: Thirty patients were enrolled on the study. The MTD was determined to be 150 mg/m2/day for 3 days. Eight of the patients completed 1 cycle of the 3 days of treatment. Of these 8 subjects, 5 (62%) had an efficacy signal. All 5 completely cleared circulating blasts. Three subjects also cleared bone marrow blasts. Of these 3, 1 went on to a successful bone marrow transplant. The other 2 had tumor lysis syndrome and unfortunately expired. Other than the tumor lysis syndromes, there was only 1 SAE definitely related to the study drug which was a grade 3 mucositis but there were also 3 other SAEs of grade 3 or 4 mucositis probably related to the study drug which comprised the MTD determination. There were no reports of cardiac toxicity. Conclusions: Nanomolecular liposomal annamycin appears to be effective through its innate resistance to MDR even as a single agent in refractory adult ALL. We are now testing it in a phase I study in children and young adults with refractory ALL or AML.

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Prevalence and therapeutic relationships of pericardial effusions in patients with leukemia
Authors: Sampat K. R. , Garcia-Gutierrez V. , Rossi A. , Pierce S. , Cortes J. , Kantarjian H. , Garcia-Manero G.
Published: August 2020

7067

Background: Little is known regarding the prevalence and natural history of pericardial disease in patients with leukemia. Recently, there have been reports of an increased incidence of pericardial effusions (PEf) in patients receiving histone deacetylase inhibitors (HDACi) such as MGCD0103. Although a direct causal relationship has not been established yet, this complication may have a significant impact for the future development of this class of drugs. To study this issue, we retrospectively analyzed a large cohort of patients with leukemia, who were evaluated at MD Anderson Cancer Center (MDACC), to determine the prevalence, timing, and characteristics of PEf in leukemia. Methods: We reviewed 3,327 patients with acute myeloid leukemia (AML, N = 1,809, 54%), acute lymphocytic leukemia (ALL, N = 494, 15%), or myelodysplastic syndrome (MDS, N =1,024, 31%), who were seen at MDACC from August 2003 to July 2008. Of this group, 1,982 patients (60%) had an echocardiogram at some point during their care at MDACC. Data regarding diagnosis, timing, effusion size, and prior therapy was collected in the 401 patients (20.2%) that had echocardiographic evidence of PEf. Results: The overall prevalence of PEf was 21.7%, 21.1%, and 19.9% (p = 0.72) in patients with AML, ALL, and MDS, respectively. In the 401 total patients with PEf, 22.8%, 25.0%, and 18.4% (p = 0.33) of these effusions were found before treatment in the three disease categories, respectively. The rest occurred after some form of chemotherapy, accounting for 77.2%, 75.0%, and 81.6% (p = 0.73) of the total PEf by disease, respectively. Most PEf were of minimal size (67%) overall. No differences in effusion characteristics, including severity, were observed among different types of therapies including HDACi. Conclusions: PEf are relatively common in patients with leukemia at initial presentation and are usually asymptomatic. Their incidence increases with therapy administration although it appears that this is not a process related to specific classes of treatment or type of leukemia.

No significant financial relationships to disclose.
The effects of sildenafil citrate on malignant B-cells in patients with chronic lymphocytic leukemia
Authors: McGregor B. A. , Gorrebeeck A. , Struble E. , Harroff A.
Published: August 2020

7076

Background: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western Hemisphere, with over 10,000 cases diagnosed annually in the United States. It is characterized by progressive accumulation of functionally incompetent long-lived lymphocytes, shown to be secondary to a defect in programmed cell death or apoptosis. The phosphodiesterase inhibitor sildenafil induces capsase dependent apoptosis of malignant B lymphocytes in vitro. This study will test the hypothesis that sildenafil reduces the expression of BCL-2 and increases the spontaneous apoptosis rate of malignant B-cells in patients with CLL. Methods: Thirteen patients with Rai Stage 0 CLL were enrolled. Nine of the patients were aged sixty-five years or older and received sildenafil 25 mg weekly; four patients were under the age of sixty-five and received sildenafil 25 mg weekly. All patients took the medication for a total of three months. Lymphocyte counts, BCL-2 expression, caspase 3 activity, and apoptosis rate were monitored on enrollment and monthly for duration of the study. Results: The median age of patients enrolled in the study was 74 with a median white blood cell count of 18 x103/mL. Twelve of the 13 patients completed three months of therapy. While one patient withdrew due to blehparitis, not felt to be a side effect of sildenafil, all other patients tolerated the medication well without any adverse effects. There was no significant decrease in white blood cell count or Bcl-2 expression; capsase 3 activity and apoptosis rates remained undetectable on presentation and throughout treatment. Conclusions: At a dose of 25 to 50 mg weekly, sildenafil does not appear to have any effects on the malignant B cells in CLL. While this dose may not produce a measurable clinical or cellular response, higher doses may still have an effect on the malignant B cells of CLL. The dose of sildenafil was based on a case series of patients with Viagra who had decreases in IgM levels while taking sildenafil 25–50 mg weekly. Subsequent studies in have shown a greater reduction in IgM in patients taking sildenafil 100 mg daily and patients did not report any significant side effects. A follow-up study using sildenafil 100 mg daily is warranted.

No significant financial relationships to disclose.
Comorbidities and prognosis of myelodysplastic syndromes
Authors: Naqvi K. , Oh J. , Garcia-Manero G. , Pierce S. , Suarez-Almazor M. E.
Published: August 2020

7086

Background: Cancer patients often experience comorbidities that may affect their therapeutic plan, prognosis, and outcome. Few studies have evaluated comorbidities in myelodysplastic syndromes (MDS). The aim of our study was to determine the effect of comorbidity on the survival of patients with MDS. Methods: We reviewed the medical records of consecutive adult MDS patients who presented to our comprehensive cancer center in 2002. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients, was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the International Prognostic Scoring System (IPSS). We also collected information on bone marrow transplantation (BMT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Results: Of the 55 patients included in this preliminary report, 41 (74.5%) were male, and 47 (85.5%) were white; mean age was 66.4 years; mean follow-up 22.2 months. The three most common comorbidities were hypertension, diabetes mellitus, and coronary artery disease. A total of 90.9% of patients had an IPSS risk of intermediate or higher. The ACE-27 comorbidity scores were as follows: none, 18 patients (32.7%); mild, 17 (30.9%); moderate, 9 (16.4%); and severe, 11 (20.0%). Fifty patients (90.9%) died, whereas 9 (16.4%) underwent BMT. Median survival according to ACE-27 scores was: 22 months for patients with no comorbidity, 11 months for patients with mild or moderate comorbidity, and 8 months for those with severe comorbidity; this trend did not reach statistical significance (p = 0.42). A linear trend was observed between the severity of comorbidity and having received BMT: half of the patients with no comorbidities received BMT compared to none in the group with a severe score (p = 0.02). Conclusions: A small trend was observed between survival and comorbidity. Most of our patients had an advanced IPSS stage which may have decreased the strength of this association. Patients with comorbid conditions received BMT less often than those without comorbidity. Further studies are needed to evaluate the effects of comorbidities on the prognosis and therapeutic options of patients with early-stage MDS.

No significant financial relationships to disclose.