bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clostridium difficile infection in acute myeloid leukemia patients.
Authors: Bal Anjali , Morris Amy , Naeem Mohammed Athar , Thomas Tanya , Keng Michael Kenneth 
Published: September 2018

e18503 Background: Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea. Studies suggest patients (pts) undergoing acute myeloid leukemia (AML) chemotherapy (ctx) are at high risk of contracting CDI, but clinical and disease characteristics are not described. This study reports CDI rates and disease characteristics in AML pts at University of Virginia (UVA). Methods: A retrospective review of consecutive pt-encounters undergoing AML ctx at UVA from 2011-2016 was conducted. The main endpoint was to determine the rate of CDI within 90 days of ctx initiation, while assessing pt characteristics, comorbidities, risk factors, and disease specific indices associated with CDI. Statistical methods include nonparametric Wilcoxon and Fisher’s exact tests, with significance defined as p-value < 0.05. Results: Of 142 pts, 44 (31%) AML pts had CDI. 7 pts (15.9%) had 1 recurrent CDI episode,;2 pts (4.5%) had more than one. 18 pts (40.9%) underwent CT imaging specifically for CDI, revealing 3 pts (6.8%) with typhilitis and 2 pts (4.5%) with toxic megacolon requiring colectomy. There was no CDI associated mortality. At CDI diagnosis, 33 pts (75%) were neutropenic and 14 pts (31.8%) received prophylactic antibiotics. Median time from ctx was 12 days. Treatment for CDI: 38 pts (86.4%) single agent metronidazole or vancomycin and 6 pts (13.6%) combination. Sixteen (36.3%) CDI pts achieved CR, while 18 (40.9%) pts relapsed from AML. Compared to non-CDI pts, CDI pts were younger (50 v 59), less obese (BMI 26 v 29), poor-risk cytogenetics (26.5% v 14.1%), CKD (6.8% v 0.7%), prior cancer (6.8% v 2.8%). No statistical difference was seen in demographics (gender, race), comorbidities (tobacco use, pulmonary and cardiac disorders), or AML characteristics (bone marrow cellularity and blast, length of stay). Conclusions: The study concludes that the incidence of CDI in AML pts undergoing ctx is greater than hospitalized patients with or without malignancy as reported in the literature. CDI incidence is increased in younger, less obese, history of CKD or cancer, and poor-risk cytogenetics, suggesting potential predictive risk factors for CDI in AML pts. Further prospective studies are needed to confirm these potential CDI risk factors.
Quality-adjusted life years (QALY) for inotuzumab ozogamicin vs standard of care for relapsed/refractory acute lymphoblastic leukemia (R/R ALL).
Authors: van Oostrum Ilse , Su Yun , Heeg Bart , Wilke Thomas , Smith Alexander , Loberiza Fausto Rodriguez 
Published: September 2018

e18506 Background: Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, has demonstrated superior clinical activity versus standard of care (SOC; intensive chemotherapy), including clinically meaningful improvement in overall survival (OS), high rates of complete remission (CR) and stem cell transplantation (SCT), and favorable patient-reported outcomes for R/R ALL in the phase 3 INO-VATE trial. Quality of life is an important consideration for R/R ALL patients in both short- and long-term survival. This study aimed to estimate mean overall survival adjusted for QoL (QALY) for patients treated with InO v SOC. Methods: A Markov model was developed with five health states - No CR, CR, post-SCT, progression, and death. Transition probabilities between health states and mortality rates were based on the InO-VATE trial. These rates were extrapolated to a lifetime horizon using parametric survival curves fitted to available OS data, and published literature for survival after SCT. Utilities (QoL valuations) for each health state were based on the patient-reported EQ-5D scores collected in the InO-VATE trial and a literature review. Adverse events experienced during and after treatments, including as a result of subsequent SCT, were taken into account in overall QoL. Outcomes were discounted at 1.5% and half-cycle corrected. Results: The estimated mean LY and QALY in each health state for InO and SOC and their differences are shown in Table. Most gains in LY and QALY for InO over SOC were from Post-SCT. Conclusions: This analysis taking into account both quantity and quality of life estimates InO offers an average of nearly 2 more years of QALY compared to SOC in R/R ALL, based on higher CR and SCT rates and better QOL. This is mainly driven by long-term gains of SCT. This can help inform patients, physicians and payers in decision making. [Table: see text]
Effect of echocardiogram prior to induction therapy for acute myeloid leukemia on detection of cardiac dysfunction and treatment modifications.
Authors: Yui Jennifer C. , Mudireddy Mythri , Patnaik Mrinal , Gangat Naseema , Al-Kali Aref , Elliott Michelle A. , Hogan William J. , Hook Carl C. , Wolanskyj Alexandra P. , Pardanani Animesh Dev , Villarraga Hector R. , Litzow Mark Robert , Tefferi Ayalew , Begna Kebede 
Published: September 2018

e18514 Background: Standard induction therapy for acute myeloid leukemia (AML) includes “cytarabine and anthracycline”. Anthracyclines are known to cause acute, subacute and chronic cardiac complications ( Lefrak , EA et al, Cancer 1973:32(2):302-314; Singal, PK et al, NEJM 1998;339(13):900-905). It is recommended to do base line cardiac function assessment with echocardiogram prior to induction therapy containing anthracycline. This study was done to find the frequency of changes made in avoiding anthracycline usage following this evaluation. Methods: The Mayo clinic data base was interrogated to identify patients with newly diagnosed AML who underwent echocardiogram prior to anthracycline containing induction chemotherapy. Echocardiogram results, including left ventricular ejection fraction (LVEF), diastolic dysfunction, valvular disease, and any resultant treatment alterations were reviewed. Results: Three hundred twenty six patients were identified. The median (range) age was 61 (17-82) years and 62% were male. The median (range) LVEF was 65% (30-87), and 3 (0.9%) patients had LVEF < 50% (range 30-47%). Of these 3 patients, 1 had 4 vessel CABG a decade ago, his EF was 46% and treated with full dose idarubicin; 2 of them presented with blastic crisis, 1 had EF 46% and improved to 51% after 5 days and then given daunorubicin, the other one had an EF of 30% and treated with 50% dose reduced cytarabine alone. Sixty five (23%) patients had previous chemotherapy or radiation exposure, including 24 (7.4 %) with previous anthracycline, 14 (4.3%) had prior radiation to the chest wall. No patient with previous chemotherapy or radiation exposure had a reduced LVEF. Conclusions: Echocardiography prior to anthracycline therapy rarely detects abnormal LVEF. Screening echo may be helpful in those presented with leukemic blastic crisis or had previous exposure to chemo-radiation.
BST-236
Authors: Zuckerman Tsila , Ram Ron , Ben Yakar Ruth , Gengrinovitch Stela , Flaishon Liat , Rowe Jacob 
Published: September 2018

e18520 Background: Cytarabine, the first-line treatment for acute myeloid leukemia (AML), is associated with severe toxicity and high treatment-related mortality (TRM), especially in older patients. Hence, while AML incidence increases with age, advanced age and comorbidities limit cytarabine administration. BST-236 is a new cytarabine pro-drug, enabling delivery of high dose cytarabine to leukemia cells with lower systemic exposure to the free drug. The aim of this study was to evaluate the safety and optimal BST-236 dose in acute leukemia patients. Methods: A Phase I/IIa prospective open label study enrolled adult relapsed/refractory or newly-diagnosed acute leukemia patients. Patients are enrolled into 6 BST-236 escalating-dose cohorts (0.3 – 6 g/m2/d). Treatment was administered as 1-hour daily infusion for 6 days. To date, 18 patients, median age 77 (27-90), were treated with up to 4.5 g/m2/day: 6 relapsed/refractory AML patients, median age 64 (27-81), and 12 newly-diagnosed, unfit for standard chemotherapy patients (7 secondary AML; 5 de novo AML/ALL), median age 79 (70-90). Results: BST-236 treatment was well-tolerated. Only 6 SAEs were assessed as possibly/probably related to BST-236, all “on-target” hematological toxicity events or bacterial infections. The 8-weeks TRM (including from disease progression) in the newly-diagnosed population was 16%. No neurological events or > grade 2 typical cytarabine events such as mucositis, diarrhea, or alopecia were reported during treatment or within 30 days of follow up. Response to the treatment was observed in 6 of the 12 newly-diagnosed patients, including 4 complete remissions (CR), with increased overall survival (OS). No response was reached in the relapse/refractory patients. Conclusions: BST-236 is safe and very well tolerated, enabling delivery of high dose cytarabine to old patients, resulting in overall response and CR rates of 50% and 33%, respectively and increased OS. Notably, 67% of the responding patients had secondary AML, refractory to hypomethylating agents. A phase II study is planned to confirm these encouraging results. Clinical trial information: NCT02544438.
Treatment patterns and characteristics of acute promyelocytic leukemia (APL) patients receiving arsenic trioxide (ATO) therapy in a real-world setting.
Authors: Tang Boxiong , Gabriel Susan , Zhou Jifang , Pathak Ashutosh K. , Irwin Debra , Riehle Ellen , Lo-Coco Francesco , Tallman Martin S. 
Published: September 2018

e18522 Background: Clinical trials have shown that low-risk APL patients had significantly better outcomes when receiving first-line all-trans retinoic acid (ATRA) + ATO compared with standard ATRA + chemotherapy. Few published studies have used real-world data to describe patients using ATO and their current treatment patterns. This study used United States (US) administrative claims data to describe treatment patterns and characteristics of patients receiving first-line ATO. Methods: This retrospective, observational cohort study used claims data from the MarketScan databases. As there is no ICD-9-CM diagnosis code for APL, ATO treatment was used as a surrogate for the diagnosis of APL since ATO is typically used only in APL patients. Patients were selected if they had ≥1 claims for ATO between January 1, 2000, and June 30, 2015. Date of first use was designated the index date. To identify first-line ATO initiation, patients with ATRA or other APL-indicated chemotherapy claims any time before the index date were excluded. Variable baseline and follow-up periods consisting of ≥3 months of pre-index and ≥30 days of post-index continuous enrollment in medical and pharmacy benefit were used. Results: In total, 331 patients were identified with a subset (n = 265) having ≥2 claims for ATO. The analysis focused on these 265 patients, 54% of whom were male. Mean age was 60.6 years; 45% were covered by Medicare. The most common comorbid conditions measured were diabetes (6%), chronic obstructive pulmonary disease (5%), and congestive heart failure (4%). The most commonly selected APL treatments administered during follow-up were ATRA (17%) and daunorubicin (9%) with the use of idarubicin, cytarabine, and mitoxantrone at less than 3%. Maintenance therapy with methotrexate or 6-mercaptopurine was observed in 7% and 6% of patients, respectively. Conclusions: This is one of the first studies to examine patient characteristics and treatment patterns for first-line ATO using real-world data. Further research is needed to evaluate outcomes for patients receiving ATO as first-line therapy and to re-evaluate treatment guidelines in light of these outcomes.
Allogenic stem cell transplant in patients over the age of 70, including octogenarians, with hematologic malignancies: A single institution experience.
Authors: Gaudet Robert E. , Cerny Jan , Ramanathan Muthalagu , Raffel Glen , Zhou Zheng , Shanahan Lindsey , Bednarik Jayde , Nath Rajneesh 
Published: September 2018

e18538 Background: Patient age is an important factor when considering allogenic stem cell transplant (aSCT) as a treatment modality for hematologic malignancies. Previous series exploring older age and outcome in aSCT have generally not included fit, older adults beyond the age of 80: a group typically considered ineligible for aSCT. This report describes our single-institution experience with aSCT in patients age 70 and older, including octogenarians, from March 2010 through April 2016. Methods: Retrospective analysis was performed on all patients older than 70 years undergoing aSCT at UMass Memorial Medical Center (UMMMC) between March 2010 and April 2016. The study was approved by the UMMMC IRB. Results: 32 patients were identified: 19 men and 13 women. 1 patient underwent a second aSCT in the study period. Median age at time of aSCT was 73 years (range 70-83). 4 patients were age >80. Diseases treated were AML (19 pts.), MDS (12 pts.), and CLL (1 pt.). 24 transplants were performed with unrelated donors: 17 with 10/10 match, 3 with 11/12 match, 3 with 10/12 match, and 1 with 9/12 match. 9 were performed with umbilical cord blood units. Grade II-IV acute GVHD developed in 9 patients (27%). Day 100 survival by age following the transplant were 11/18 (61%) for patients aged 70-75, 6/10 (60%) for patients aged 75-80 and 4/4 (100%) for patients aged 80-85. Conclusions: Allogenic Stem Cell Transplant is a viable treatment modality in highly-selected elderly patients with hematologic malignancies. Further studies are warranted in a prospective fashion. [Table: see text]
Cost effectiveness of G-CSF after allogeneic peripheral blood stem cell transplant.
Authors: Singh Vijendra , Kim Seongho , Jang Hyejeong , Alavi Asif , Bhutani Divaya , Ayash Lois Jeanne , Ratanatharathorn Voravit , Uberti Joseph P. , Deol Abhinav 
Published: September 2018

e18540 Background: In spite of the fact G-CSF has been used post stem cell transplant (SCT) to accelerate neutrophil engraftment its use post allogeneic SCT remains controversial. ASCO does not recommend its use after allogeneic SCT. To further evaluate the effectiveness of its use, we compared outcomes in pts who underwent related and unrelated peripheral blood SCT(PBSCT) either with or without the use of G-CSF post SCT. Methods: This is a retrospective study comparing early outcomes in pts who received G-CSF starting on day + 6 post SCT until engraftment with pts who did not receive a planned course of G-CSF. Pts who underwent Allogeneic PBSCT between 2012-2014 at our institution were included. Pts who received marrow, haploidentical or cord blood transplants were excluded. Associations with survival outcomes were assessed by univariable and multivariable Cox proportional regression models. Results: A total of 162 patients were evaluated. Sixty-five pts received G-CSF post SCT and 97 did not. The only difference between the two groups was that more pts in the G-CSF group received myeloablative-conditioning (MAC) regimen (78% vs. 55%, p = 0.008). Other pt characteristics were not significantly different. Length of hospital stay was significantly lower in the G-CSF group (24 vs. 27 days P = 0.002). Pts who received G-CSF had earlier neutrophil engraftment (median, days 11 vs. 14 p = < 0.001). The median day of platelet engraftment was 15 days in both groups. There was no significant difference between the 2 groups in re-admissions in the first 100 days, and the incidence of acute or chronic GVHD. In multivariate analysis use of G-CSF did not significantly impact non- relapse mortality, relapse free survival and overall survival. However, relapse rate was significantly lower in G-CSF group in multivariable analysis (hazards ratio = 0.44, p = 0.03). Conclusions: Use of G-CSF post allogeneic PBSCT is associated with earlier neutrophil engraftment, shorter hospital stay and a suggestion of a reduced relapse rate after PBSCT. Our experience suggests that use of G-CSF (on average for approximately 5 days) in this setting is cost effective as it reduces hospitalization duration without adversely impacting post-transplant outcomes.
Nationwide in hospital outcomes of allogenic hematopoietic cell transplant (AHCT) in acute myeloid leukemia (AML).
Authors: Yogarajah Meera , Muthu Johnn 
Published: September 2018

e18542 Background: AHCT is the definitive treatment for AML with unfavorable risk however with increased morbidity and mortality limiting its use in adults above 60 years of age. National in patient sample (NIS) database was analyzed to study trends and predictors of mortality in AML patients receiving AHCT. Methods: NIS database includes 20% of all hospitalizations in USA. NIS database from 2010 - 2014 was analyzed. ICD-9 codes were used to extract patients and to analyze demography, comorbidities, complications and outcomes. A multivariable logistic regression was performed to identify predictors of mortality. Results: 1755 patients with AML and AHCT were identified from the database. Males 55.2%, median age 52, age >60 years 35%, Whites 80.6%, Blacks 5.5%, Hispanics 6.7% and others 7.2%. Median length of stay was 26 days. Inpatient mortality showed a decreasing trend from 2010 to 2014 (6.7%, 4.6%, 3.9%, 4.8%, 4.6%) likely due to better supportive care. p (trend) = 0.29. Univariate analysis for age >60 years did not show increase in mortality however multivariate analysis did show increase in mortality (Odds ratio 2.281, p = 0.006). Other predictive factors of increased mortality were presence of complications of AHCT. Infection (OR 8.392, p < 0.001), acute graft versus host disease (GVHD) (OR 2.139, p = 0.033) and pneumonia (OR 3.584, p <0.001) were associated with increased mortality. Independent predictive factors of mortality were renal failure (OR 14.186, p < 0.001) and liver disease (OR 3.228, p < 0.001). Conclusions: Age more than 60 by itself is not associated with increased mortality in the absence of complications and comorbidities. Infection is a major predictor of mortality. [Table: see text]
Comparison of digital PCR with real-time PCR calibrated to the International Scale for BCR-ABL monitoring.
Authors: Shah Parth , Cossor Furha Iram , Murarka Shiva , Dixit Hemangi 
Published: September 2018

e18545 Background: Monitoring BCR-ABL1 fusion transcripts is the cornerstone of management in chronic myeloid leukemia (CML). Real Time PCR(RTPCR) has been the tool of choice for its sensitivity and dynamic range. The International Scale was recently introduced to allow for standardization across laboratories. Chip based Digital PCR(dPCR) which allows for absolute quantitation may obliviate the need for such standardization by giving absolute results.It has the potential to increase sensitivity for detection of minimal residual disease. This assumes great significance as we move into the era of treatment free remission. Methods: A total of 31 EDTA-blood samples of CML patients with known values ranging from 0.003-0.5 IS were processed via an accredited RTPCR protocol calibrated to the IS scale and a parallel dPCR workflow without any specific calibration . The analysis of digital PCR samples was performed on the Thermofisher Cloud Platform. Results: Both RTPCR and dPCR yielded extremely concordant results. The Pearson correlation between the two methods was r = 0.6043 (95%CI: 0.318 to 0.789; p = 0.0003). The calculated BCR-ABL/ABL ratios were comparable with a median of 0.098 for RT-PCR calibrated to the IS (range 0.003-0.55; n = 26) and 0.11 for dPCR (range 0.003-0.37; n = 29). The mean difference for the ratios between the two methods used for the detection was around 0.08. Conclusions: We demonstrate here the capability of dPCR to provide a parallel result to an IS scale calibrated protocol without any standardization. This approach required no specific calibrators or standards and resulted in extremely cost effective testing. This freedom from routine calibration provides for a significantly more robust workflow and greatly increased reliability. Limitations do persist in dPCR on account of limited chip densities which are the main parameter for the Poisson statistics. This has limited the dynamic range on dPCR to a maximum of Log 4 for accurate quantification. However as chip densities and emulsion concentrations increase in these technologies, they are poised to introduce a new era in the quest of accurate quantification.
Improving diagnostic and prognostic accuracy of myeloid neoplasms (MNs) by next generation sequencing.
Authors: Schwartz Candice , Macklis Jason Nathaniel , Buckingham Lela , Shammo Jamile M. 
Published: September 2018

e18567 Background: Molecular aberrations in MNs have been well described. Driver mutations such as JAK2, MPL, and CALR, are pathognomonic for MNs, whereas other somatic mutations are less specific but have prognostic significance. Multi-gene panel testing for known somatic mutations has been utilized for diagnostic and prognostic purposes, and testing for somatic mutations to identify clonal hematopoiesis has been adopted by the WHO 2016 classification of myeloid malignancies. We sought to assess the impact of testing for somatic mutations by NGS on diagnosis and management of pts with MNs. Methods: We employed a myeloid panel (MP) of 40 commonly mutated genes involving RNA splicing, chromatin remodeling, and signaling pathways. Testing was performed on ptswho presented to the clinic between 2/2015 and 12/2016. Initial diagnosis and rationale for testing (diagnostic or prognostic) were recorded. We then determined whether the MP resulted in a change in diagnosis, prognosis, or management. Results: 55 pts with a known or suspected MN had a MP performed.Diagnoses at presentation were: MDS (27), MF (8), MPN-U (8), MDS/MPN (4), multiple diagnoses (2), and no definitive diagnosis of MN (6). 87% (48/55) of pts had at least one somatic mutation.In 13 pts (23.6%) the MP led to a definitive diagnosis or a change in diagnosis. For example, 2 pts initially diagnosed with MPN-U were diagnosed with CNL after detection of CSF3R mutation. All 4 pts initially diagnosed with MDS with fibrosis were subsequently diagnosed with primary myelofibrosis; 3 had a MPL mutation and 1 had a CALR mutation. Management was altered in 12 pts (21.8%) and prognosis was changed in 11 pts (20.0%). For example, 2 pts were treated with a JAK-2 inhibitor and 2 pts with low risk MDS were referred for transplant evaluation due to the presence of a TP53mutation. Conclusions: Our study confirms that panel testing meaningfully improves diagnostic accuracy and provides prognostic value. In total, the MP resulted in a change in diagnosis, prognosis, or management in 43.6% (24/55) of cases. Confirmation of these observations merits prospective evaluation for a larger number of pts.