bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the impact of early versus late inpatient palliative care consultation for cancer patients.
Authors: Cassel Brian , Coyne Patrick J. , Skoro Nevena , Kerr Kathleen , Del Fabbro Egidio 
Published: March 2020

6638 Background: Access to specialist palliative care (hospital-based or hospice) is a recognized measure of quality in cancer care. Most cancer centers do have palliative care consult services, although the availability of a comprehensive program that includes a palliative care unit and outpatient clinic (Hui 2010) is inconsistent. A simultaneous integrated model of palliative care that facilitates earlier access to a specialized palliative care team may improve clinical outcomes. Palliative care programs should measure the access, timing and impact of their clinical service. Methods: Hospital claims data were linked to Social Security Death Index (SSDI) data from the US Department of Commerce. 3,128 adult cancer patients died between January 2009 and July 2011 and had contact with our inpatient palliative care team in their last six months of life. We determined whether IPC earlier than 1 month prior to death had an impact on hospitalizations, in-hospital mortality and referral to hospice. Results: 27.5% of cancer decedents accessed IPC, median of 22 days before death. 13.2% were discharged to hospice, median of 13 days before death. Patients with IPC earlier than 1 month until death were more likely to have hospice and fewer in-hospital deaths but there was no association between early IPC and a 30-day mortality admission. Conclusions: Palliative care services are accessed by a minority of patients and typically in the last 2-3 weeks of life. Although in-hospital deaths were reduced by earlier palliative care consultation, 30 day mortality did not improve. Hospitals may need to implement other strategies including early integration of outpatient palliative care among cancer patients, to achieve an impact on 30-day mortality admissions. [Table: see text]
Allogeneic transplantation for myelofibrosis: Benefit of dose intensity.
Authors: Popat Uday R. , Bassett Roland , Chen Julianne , Alousi Amin Majid , Anderlini Paolo , Ciurea Stefan O. , Hosing Chitra , Jones Roy B. , Kebriaei Partow , Khouri Issa F. , Konoplev Sergej , De Lima Marcos , Nieto Yago , Oran Betul , Qazilbash Muzaffar H. , Rondon Gabriela , Shpall Elizabeth J. , Verstovsek Srdan , Andersson Borje , Champlin Richard E. 
Published: March 2020

7011 Background: We did a prospective study of busulfan (bu) and fludarabine (flu) conditioning in patients with myelofibrosis. After observing a high relapse rate in the initial cohort, we increased the intensity of conditioning regimen for subsequent patients, hypothesizing that increased dose intensity delivered with PK guidance will reduce relapse rate without increasing non relapse mortality (NRM), thereby improving overall outcome. Methods: Patients with intermediate or high risk MF were eligible if they had adequate organ function and at least 9/10 matched related or unrelated donor. Of the 46 consecutive patients, 15 (bu low group) received IV busulfan 130 mg/m2 x 2 (day -3,-2). Of the remaining 31 (bu high group), 27 received IV busulfan dose to a target daily AUC of 4000 μmol.min x 4 (day -5 to -2) and 4 patients received a fixed dose of 100 mg/m2 x 4 (days -5 to -2). All patients received fludarabine 40mg/m2x 4 (day -5 to -2). Results: 23 males and 23 females with a median age of 58 years (27-74) had intermediate (25) or high-risk (21) disease. Donors were matched sibs (19), matched unrelated (23), or mismatched unrelated (4). With a median follow-up of 2.1 years (range 0.1-6 years), 3-year overall survival(OS), event-free survival (EFS), cumulative incidence (CI) of non-relapse mortality (NRM), and CI of relapse were 69%, 50% , 13%, and 37%, respectively. Multivariate Cox regression analysis showed that Bu-high dose (HR 0.41; p=0.04) and peripheral blood CD 34 count (HR 1.7; p=0.03) were significantly associated with EFS, and high CD-34 count was significantly associated with OS (HR 1.87; p=0.04). Table shows details of 3-year outcomes of low-dose and high-dose group. All patients engrafted with a median time to neutrophil engraftment of 13 (0-27) days and a median time to platelet engraftment of 24 (0-268) days. Cumulative incidence (CI) of grade II-IV, grade III, IV acute GVHD, and Chronic GVHD were 22%, 5%, and 39%, respectively. Conclusions: Higher dose busulfan, delivered with pharmacokinetic dose adjustment, reduces relapse without increasing non-relapse mortality, resulting in better EFS in patients with MF. Clinical trial information: NCT00475020. [Table: see text]
Efficacy and safety of cladribine: Subcutaneous versus intravenous administration in hairy cell leukemia.
Authors: Mohamed Tarek Yakout , El Gammal Mosaad , Namour Alfred Elias , Abdel Malek Raafat Ragaie , Khorshid Ola 
Published: March 2020

7013 Background: Hairy cell leukemia (HCL) is rare B-cell lymphoproliferative disorder. Its treatment has evolved from splenectomy with time to failure (TTF) of 19 months to Cladribine that increased complete remission (CR) rate to 90%, with only small percentage of patients relapsing at 30 months. Cladribine (CDA) is originally administered intravenously as continuous infusion for 7 days; Subsequently, it was administered subcutaneously. This study aims at comparing efficacy and toxicity of Subcutaneous (SC) versus Intravenous (IV) administration of CDA in treatment of HCL. Methods: This retrospective study included HCL patients presented to National Cancer Institute and Nasser Institute, Cairo, Egypt, during period 2004-2010. Included patients received CDA as 1st or 2nd line with minimum follow up of 12 months. All files were reviewed for baseline clinical & laboratory parameters, route of administration, response, adverse events and survival. Results: This study included 49 eligible patients, 41 patients received CDA as 1st line treatment, while 8 patients as 2nd line. Eighteen patients were treated by continuous IV infusion whereas 31 patients by SC injections. Both groups were comparable regarding baseline clinical and laboratory parameters with no statistically significant difference. At median follow up period of 33.5 months, complete remission rate was 94% in IV group versus 97% in SC group (p=0.691); median TTF for IV group was 52.9 months while that for SC group was not reached (p=0.035). The median time to achieve CR in both arms was similar. By analyzing different factors affecting TTF using multivariate analysis, route of administration proved to be the only statistically significant factor (P=0.006). Regarding adverse events, there was no difference between both groups in hematological toxicities. IV route was associated with a significant higher incidence of mucositis (p=0.02) and viral infections (p=0.01). Hepatotoxicity and neurotoxicity were higher in SC group but difference was not statistically significant. Conclusions: SC administration of cladribine is an alternative route to IV in treatment of HCL with similar response rate, longer time to treatment failure and better tolerability.
A comprehensive prognostic index for patients with CLL.
Authors: Pflug Natali , Bahlo Jasmin , Shanafelt Tait D. , Eichhorst Barbara , Bergmann Manuela , Elter Thomas , Bauer Kathrin , Malchau Gebhart , Rabe Kari G. , Stilgenbauer Stephan , Dohner Hartmut , Jäger Ulrich , Eckart Michael , Hopfinger Georg , Busch Raymonde , Fink Anna-Maria , Wendtner Clemens M. , Fischer Kirsten , Kay Neil E. , Hallek Michael 
Published: March 2020

7015 Background: Besides clinical staging, a number of biomarkers predicting OS in CLL have been identified. The multiplicity of markers, limited information on their independent value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We developed an integrated prognostic index using the database of the German CLL Study Group (GCLLSG), which was subsequently validated in a cohort of untreated CLL patients (pts) from the Mayo Clinic. Methods: The analysis was based on a dataset collected between 1997 and 2006 in 3 GCLLSG phase III trials. The external validation was performed on a series of newly diagnosed CLL pts managed at Mayo Clinic. Results: The GCLLSG dataset (1,948 physically fit pts at early and advanced stage; median age: 60 yr (range 30-81); median observation time 63.4 mo) was used as a training dataset. 7 parameters were identified as independent predictors for OS: sex, age, ECOG status, del 17p, del 11q, IGHV mutation status, thymidine kinase and β2-microglobulin. By using a weighted grading a prognostic index was derived separating four different pts groups: low risk (score 0 - 2), intermediate risk (score 3-5), high risk (score 6-10) and very high risk (score 11-14) with significant different OS rates (95.2%, 86.9%, 67.7% and 18.7% OS after 5 yr for the low, intermediate, high and very high risk group respectively (p<0.001). This prognostic index was validated in a cohort of 676 newly diagnosed, untreated pts from the Mayo Clinic (median age 61.5 yr (range 32 - 89); median observation time 47.0 mo). The 4 risk groups were reproduced with 98.3%, 95.4%, 75.4% and 10.8% OS after 5 yr. The prognostic index predicts OS independent of Rai/Binet stage and provides accurate estimations regarding time to first treatment (TTF). C-statistic is 0.75. Conclusions: Using a multi-step process including external validation, we developed a comprehensive prognostic index combining clinical, serum, and molecular information into a single risk score for pts with untreated CLL. The prognostic index provides more accurate prediction of both TTF and OS. To our knowledge it is the first prognostic model in CLL to reach the C-statistic threshold (c > 0.70) necessary to have utility at the level of the individual.
Which treatment options impact outcomes in elderly chronic lymphocytic leukemia patients with high prevalence of comorbidity?
Authors: Satram-Hoang Sacha , Reyes Carolina M. , Hoang Khang , Momin Fayez , Guduru Sridhar , Skettino Sandra L. 
Published: March 2020

7016 Background: Therapy selection in chronic lymphocytic leukemia (CLL) patients is based on disease severity as well as patient characteristics such as age and comorbidity. While treatment outcomes are mostly available from clinical trial data in younger patients, less is known about the effect of comorbidities on outcomes in elderly CLL patients in the real-world setting. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was utilized in this retrospective cohort analysis of 3,366 first primary CLL patients. Patients were diagnosed between 1/1/1998-12/31/2007, were >66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received first-line treatment with any oral or infused therapy. CLB is covered by Medicare Part D and data for its use were only available from 2007-2009 in the dataset. Cox regression with backward elimination and propensity score weighted Cox regression estimated the relative risk of death. Date of last follow-up was 12/31/2009. Results: There were 153 CLB, 606 R-mono, 702 R+IV Chemo, and 1,905 IV Chemo-only patients. CLB and R-mono patients were older at diagnosis with mean age of 77 compared to R+IV Chemo (73 years) and IV Chemo-only (76 years; p<.0001). Patients administered R-mono had a higher comorbidity burden and more advanced disease compared with other treatment groups. In the survival analysis we compared CLB to R-mono during the time period 2007-2009 and R+IV Chemo to IV Chemo-only during the time period 1998-2009. The adjusted multivariate survival analysis revealed a significant mortality risk reduction with R+IV Chemo compared with IV Chemo-only patients (HR, 0.72; 95% CI, 0.62-0.84) while a non-significant mortality risk reduction was noted with R-mono compared to CLB patients (HR, 0.47; 95% CI, 0.21-1.05). Older age and increasing comorbidity score were significantly associated with higher mortality. Conclusions: These findings suggest that chemo-immunotherapy is more effective than chemotherapy in an elderly population with a high prevalence of comorbidity. This extends the conclusions from clinical trials in younger, medically fit patients.
Effect of quizartinib (AC220) on response rates and long-term survival in elderly patients with FLT3-ITD positive or negative relapsed/refractory acute myeloid leukemia.
Authors: Martinelli Giovanni , Perl Alexander E. , Dombret Hervé , Kayser Sabine , Steffen Bjoern , Rousselot Philippe H. , Estey Elihu , Burnett Alan K. , Shah Neil P. , Gammon Guy , Trone Denise , Levis Mark J. , Cortes Jorge E. 
Published: March 2020

7021 Background: Advanced age and FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) in acute myeloid leukemia (AML) are associated with early relapse after standard chemotherapy and poor survival. Quizartinib (AC220), an oral FLT3 inhibitor active against ITD mutant and wild type FLT3, has shown promising activity in Ph 1 and 2 studies. Methods: Patients (pts) in a Ph 2 open label study (N = 333) of quizartinib monotherapy included 154 aged ≥60 y with known FLT3-ITD status and AML relapsed in <1 y or refractory to 1st line chemotherapy. Median duration of treatment was 14.2 wks (range 0.1–70.6 wks) for FLT3-ITD(+) pts and 9.5 wks (range 1.1–77.0 wks) for FLT3-ITD(-) pts. The composite complete remission (CRc) rate included complete remission (CR), complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete hematologic recovery (CRi). Results: Of 110 FLT3-ITD(+) pts, 63 (57%) had a CRc (3 CR, 4 CRp, 56 CRi). Of 44 FLT3-ITD(-) pts, 16 (36%) had a CRc (2 CR, 1 CRp, 13 CRi). Median overall survival (OS) in FLT3-ITD(+) pts was 25.3 wks and 16/110 (15%) survived >52 wks. The median age of these pts surviving >52 wks was 69.5 y (range 66–80 y) and median OS was 76.3 wks (range 56.9–96.0 wks). All of these pts responded to quizartinib (2 CR, 2 CRp, 8 CRi, 4 partial remission [PR]). 2 pts were still alive >1 ½ y (OS 93.0 and 96.0 wks). Median OS in FLT3-ITD(-) pts was 19.1 wks and 6/44 FLT3-ITD(-) pts (14%) survived >52 wks. The median age of these pts was 70.0 y (range 65–77 y) and their median survival was 76.6 wks (range 54.9–98.4 wks). 5 of these pts responded to quizartinib (1 CR, 3 CRi, 1 PR). Conclusions: These data for an FLT3-targeted agent show encouraging survival in a subset of elderly pts with relapsed/refractory FLT3-ITD(+) AML. Clinical trial information: NCT00989261. [Table: see text]
Phase II study of combination of hyperCVAD with ponatinib in frontline therapy of patients (pts) with Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL).
Authors: Jabbour Elias , Kantarjian Hagop M. , Thomas Deborah A. , Ravandi Farhad , Cortes Jorge E. , Faderl Stefan , Pemmaraju Naveen , Kadia Tapan M. , Garris Rebecca S. , Garcia-Manero Guillermo , Borthakur Gautam , Wierda William G. , O'Brien Susan Mary 
Published: March 2020

7024 Background: Combination of chemotherapy with TKIs was evaluated and appears to be effective in Ph+-ALL. Ponatinib is a more potent inhibitor and suppresses the T315I clones, a common cause of relapse in pts with Ph+- ALL. Clinical trials of ponatinib have demonstrated its high activity and limited toxicity in pts with Ph+-leukemia failing 2-3 TKIs and in those with a T315I mutation. Combinations of chemotherapy regimens and ponatinib may be associated with better response rates and higher likelihood of eradication of MRD. Methods: In this phase II trial, pts with newly diagnosed Ph+ ALL receive ponatinib 45 mg po QD for the first 14 days of cycle 1 then continuously for the subsequent 7 cycles. Pts in CR receive maintenance with ponatinib 45 mg po QD and vincristine and prednisone monthly for 2 years followed by ponatinib indefinitely. MRD monitoring is conducted. Results: To date 20 pts with untreated Ph+ ALL have received a median of 6 cycles; 5 pts are receiving maintenance in CR. Median age is 49 years. Median WBC at diagnosis was 2.45 x 109/L. All pts were in CR after 1 cycle. 15 of the 17 pts (88%) known to be Ph+ by cytogenetic analysis at baseline achieved CCyR after 1 cycle; 1 had mCyR only and 1 had no cytogenetic analysis at CR, both of them achieved CCyR after cycles 2; 3 had a diploid karyotype at the start. To date, 17 pts (85%) have achieved MMR, of whom 11 (55%) have achieved CMR at a median of 10 weeks from initiation of treatment. MRD assessment by flow cytometry is negative in 18 (90%) pts at a median of 3 weeks. Median time to neutrophil and platelet recovery for cycle 1 was 18 and 22 days, and 16 and 22 days for subsequent cycles, respectively. Grade ≥3 toxicity included increase of LFT’s/hyperbilirubinemia in 8 pts, thrombosis in 3, skin rash in 2, pancreatitis in 1, and pericardial effusion in 1. With a median follow up of 6 months, 19 pts are alive and in CR; 1 pt died in CR from an unrelated cardiac event. 1 pt has undergone an allogeneic transplant. The 1-year PFS and OS rates were 100% and 95%, respectively. Conclusions: The combination of hyperCVAD with ponatinib is safe and highly effective in achieving molecular remissions in pts with Ph+ ALL. Clinical trial information: NCT01424982.
Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens.
Authors: Khera Nandita , Emmert Amy , Storer Barry , Sandmaier Brenda M. , Alyea Edwin , Lee Stephanie 
Published: March 2020

7034 Background: Reduced intensity (RIC) conditioning regimens have allowed older patients and those with comorbidities to receive hematopoietic cell transplantation (HCT). Methods: We analyzed medical costs from the beginning of conditioning to 100 days after HCT for 484 patients who underwent a RIC allogeneic HCT at Fred Hutchinson Cancer Research Center (FHCRC; n=147) and Dana Farber Cancer Institute (DFCI; n=337) from 1/2008 to 12/2010. Costs up to 2 years after HCT were analyzed for DFCI (n=311) as most patients receive their post-transplant care there. Multiple linear regression was used to analyze the association between clinical variables and costs. Results: Disease distribution and transplant characteristics were comparable between the two sites, though significant differences were seen in age distribution (88% FHCRC patients ≥ 50 years vs. 80% at DFCI, p=0.04) and pre-transplant performance scores (63% patients with Karnofsky score≥ 90 at FHCRC vs. 47% at DFCI; p=0.006). Median costs for first 100 days in 2010 $ at FHCRC and DFCI were $129 000 (range 31,000-352,000) and $96,000 (3,000-614,000) respectively, p=0.0002, but differences were not significant in multivariate analysis. Inpatient costs accounted for 42% of early costs at FHCRC and 87% at DFCI.Significant predictors for early costs included a diagnosis of lymphoma/ myeloma (17% decrease in costs; p=0.01), donors other than matched related (50 -100% increase; p<0.001), relapse (17% increase, p=0.04) and ≥ grade II acute GVHD (37% increase; p<0.001). Median costs between d100 and 2 years were $39,000 (0-976,000) at DFCI. 39% of the 2 year costs occurred after first 100 days. There was no association of late costs with pre-transplant variables, and only death was associated with higher costs (138% increase; p=0.005). Conclusions: After adjustment for pre and post HCT variables, the overall costs of the RIC allogeneic transplants were similar between the two institutions despite different management approaches (inpatient vs. outpatient conditioning) and accounting methodologies. Use of unrelated/ alternative donors, relapse and acute GVHD were predictors for higher early costs while only death was associated with higher late costs.
Comparison of four different strategies of stem cell mobilization in patients with multiple myeloma.
Authors: Sivik Jeffrey Michael , Whaley Sesilya , Mierski Joseph , Castellani William J. , Lowe Mitzi , Zhu Junjia , George Melissa , Rybka Witold B. , Talamo Giampaolo 
Published: March 2020

7039 Background: There is no consensus among institutions for the optimal strategy of peripheral blood stem cell (PBSC) collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Methods: We retrospectively analysed the outcomes of PSBC collection in MM patients using the following mobilization regimens: cyclophosphamide 5,000 mg/m2 + etoposide 1,000 mg/m2 + G-CSF 5 mcg/Kg/day (Group A, n = 49); cyclophosphamide 2,000-3,000 mg/m2+ G-CSF 5 mcg/Kg/day (Group B, n = 25); G-CSF 16 mcg/Kg/day (Group C, n = 21); G-CSF 16 mcg/kg/day + plerixafor 0.24 mg/Kg (Group D, n = 128). Results: The median number of PBSC collected was 28.1 (range, 2.1-134), 4.5 (0.1-39.7), 4.0 (0-7.3) and 8.4 (0.2-41.2) million CD34+/kg in groups A, B, C and D, respectively (p <0.001). The mean number of collection days was 1.3, 2.2, 2.4, and 1.3 in groups A, B, C, and D, respectively (p <0.001). Febrile neutropenia occurred in 16 (32.7%), 1 (4%), 0, and 0 patients in groups A, B, C, and D, respectively. One patient who received CTX 3 g/m2 died of septic shock during the neutropenic phase. Failure to collect PBSC, defined as <2x106 CD34+ cells/Kg for a planned single ASCT or <4x106 for planned tandem ASCTs, was observed in 2/49 (4%), 5/25 (20%), 4/21 (19%), and 9/128 (7%) patients in groups A, B, C, and D respectively (p=0.037). Conclusions: Plerixafor + G-CSF provided the greatest benefit to risk ratio for PSBC collection in MM patients.
Management of chronic myeloid leukemia in chronic phase (CML-CP) by American Hematology-Oncology Physicians (AHOP's): Diagnostic and treatment preferences after first-line imatinib (2010-2012).
Authors: Foran James M. , Williams Michael E. , Willey Joanne , Green Mark R. 
Published: March 2020

7046 Background: In CML-CP there is perceived complexity in risk stratification at diagnosis, and in testing for BCR-ABL kinase domain mutation (KD mut, including T315I) at relapse. We sought to understand AHOP practices in the context of NCCN and European LeukemiaNet guidelines. Methods: Between 2010 and 2012, we studied time dependent practice preferences of n=1,335 AHOP’s using a proprietary, live, case-based market research tool. A core case scenario and variations based on available diagnostic & treatment options were constructed. Preference data were acquired using blinded audience response technology. All responses for each scenario were obtained contemporaneously prior to any display of summary respondent selections. All sources of research support were double blinded. AHOP's were presented with a scenario of 59-year old CML-CP patient, then indicated preferred management from up to 9 relevant available/emerging diagnostic or therapeutic options following relapse after 1st-line imatinib. Results: The majority of AHOP’s in 2012 either did not calculate (52%), or were unfamiliar (21%) with Sokal or Hasford risk stratification score. Diagnostic preferences following relapse from 2010-12 are noted in Table (distribution over time, p<0.0001). If T315I was then detected in scenario, we noted marked differences in subsequent treatment preference in 2012 vs. 2011, respectively: decreased AlloBMT (16% vs. 32%); & increased 2nd-line dasatinib (26% vs. 14%) or bosutinib (12% vs. 8%) vs. nilotinib (8% vs. 20%) despite lack of efficacy for each in T315I. Preference increased slightly for ponatinib (16% vs. 14%), but not for omacetaxine (2% vs. 6%). Conclusions: Most AHOP’s do not apply risk stratification. Increasing preference for KD mut panel testing at relapse conforms to guidelines, although not all AHOP’s test. Heterogeneity in T315I treatment suggests uncertainty or unfamiliarity with newer agents, and evidence-based efforts are needed to improve awareness. [Table: see text]