bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unplanned hospitalizations among gastrointestinal cancer patients in the state of Texas.
Authors: Manzano Joanna-Grace , Luo Ruili , Elting Linda S. , Suarez-Almazor Maria 
Published: March 2020

6634 Background: Hospitalization rates and cost of care for patients with Gastrointestinal (GI) malignancies are among the highest in the spectrum of cancers. It is poorly understood if these are driven by planned or unplanned hospitalizations. Methods: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data to describe the patterns of unplanned hospitalization among GI cancer patients in Texas. Our outcome, unplanned hospitalization, was defined as any emergent or urgent admission. Prior comorbidities were assessed using a modified Charlson score. Data were collected for 2 years from date of cancer diagnosis. Modified Poisson regression model was used to identify factors associated with the outcome. Results: 30,199 patients aged >66 years were included in the study. 25,096 patients had 70,256 in-patient claims. 53.6% of these claims were unplanned hospitalizations. The top 3 reasons for unplanned hospitalization were pneumonia, congestive heart failure and volume depletion. Unplanned hospitalization rates ranged from 57.9% (colon) to 67.4% (esophageal) among the different cancer types. After multivariate analysis, unplanned hospitalization was more likely among those with esophageal cancer (RR=1.15, CI 1.1-1.2), gastric cancer (RR=1.07, CI 1.04-1.11), pancreatic cancer (RR=1.04, CI 1.01-1.07) and rectal cancer (RR= 1.03, CI 1.00-1.06). Patients with regional and distant disease were at higher risk for unplanned hospitalization (RR=1.14, CI 1.11-1.16 and RR=1.13 CI 1.1-1.16 respectively), as well as those aged >80 (RR=1.04 CI 1.01-1.06), of black race (RR=1.06, CI 1.02-1.09), and living in census tract with >21% poverty level (RR=1.06 CI 1.03-1.09). Risk of unplanned hospitalization also increased with Charlson scores (p<.0001). Conclusions: The majority of hospitalizations were unplanned. Top reasons for unplanned hospitalization were diagnoses that are considered potentially preventable, and should be a focus for intervention. The disparity in unplanned hospitalizations among blacks and those living in poverty-stricken areas warrants further investigation as to whether this finding correlates with timely access to outpatient care in this population.
Response rate and bridging to hematopoietic stem cell transplantation (HSCT) with quizartinib (AC220) in patients with FLT3-ITD positive or negative relapsed/refractory AML after second-line chemotherapy or previous bone marrow transplant.
Authors: Cortes Jorge E. , Perl Alexander E. , Dombret Hervé , Dohner Hartmut , Steffen Bjoern , Rousselot Philippe H. , Martinelli Giovanni , Estey Elihu , Shah Neil P. , Burnett Alan K. , Gammon Guy , Trone Denise , Levis Mark J. 
Published: March 2020

7012 Background: FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in acute myeloid leukemia (AML) is associated with early relapse after chemotherapy and poor survival. Relapse after HSCT or failure of salvage chemotherapy in FLT3-ITD AML is rarely associated with subsequent HSCT or durable survival. Quizartinib, an oral FLT3 inhibitor, shows promising activity; a Ph 2 study (n=333) of quizartinib monotherapy (Levis et al, ASH 2012) reported that quizartinib often bridged patients (pts) to HSCT. Methods: 136 FLT3-ITD(+) and 40 FLT3-ITD(-) pts, relapsed/refractory after HSCT or 1-second line regimen, were included. The response category of composite complete remission (CRc) comprised complete remission [CR] + complete remission with incomplete platelet recovery [CRp] + complete remission with incomplete hematologic recovery [CRi]. Results: Quizartinib was discontinued for HSCT in 47/136 FLT3-ITD(+) pts (35%), with 44/47 having at least a PR (2 CRp, 24 CRi, 18 PR). Median overall survival (OS) was 41.5 wks for pts with CRc prior to HSCT and 29 wks for pts with PR. The 1y survival rate was 39% for both response groups. Pts with a CRc (n=36) or PR (n=20) but no HSCT, respectively, had a median OS of 24.5 and 20.9 wks and 1y survival rates of 25% and 5%. Of 27 pts with OS >52 wks, 17 (63%) had HSCT. Quizartinib was discontinued for HSCT in 14/40 FLT3-ITD(-) pts (35%), with 13/14 having at least a PR (1 CR, 1 CRp, 7 CRi, 4 PR). Median OS was not yet reached for pts with CRc, and was 40.7 wks for pts with PR. The 1y survival rate was 78% for pts with CRc and 50% for pts with PR. 8 of these 14 pts had detectable ITD mutation but the level was below the prespecified 10% cutoff. Conclusions: Of clinical significance in these heavily pretreated pts who had failed salvage chemotherapy or HSCT, approximately 1/3 were successfully bridged to potentially curative HSCT, with encouraging 1y survival rates. To extend the potential benefits of FLT3 inhibitor therapy in combination with allogeneic HSCT, studies of maintenance quizartinib to prevent relapse post HSCT are ongoing. Clinical trial information: NCT00989261.
BH3 profiling as a predictive biomarker for response to cytarabine-based treatment of acute myelogenous leukemia.
Authors: Pierceall William E. , Carlson Nicole E. , Richard David J. , Huang Xuelin , Elaschoff Michael , Konopleva Marina , Kornblau Steven Mitchell , Cardone Michael H. , Andreeff Michael 
Published: March 2020

7022 Background: Acute myelogenous leukemia (AML) is the most frequently diagnosed of the leukemias with approximately 13,000 new cases per year in the U.S. Although intense therapeutic discovery efforts have been directed towards AML, cytarabine-based treatment remains unchanged as the standard-of-care (SOC). As patient response to SOC is variable, segregating patients based on biomarker-driven predicted response may lead to improved clinical outcomes. One personalized diagnostic approach that may provide actionable information in patient management is BH3 profiling, a surrogate functional biomarker assay that assesses cell mitochondrial response to pro-apoptotic signaling. Methods: Blinded to outcomes, we profiled an AML cohort (n=63) treated with cytarabine-based therapy using a panel of BH3 peptides with response as a primary endpoint. Peripheral blood mononuclear cell (PBMC) or bone marrow aspirate (BM) specimens were obtained from newly diagnosed AML patients and viably preserved. Specimens were assayed by flow cytometry following cell permeabilization and incubation with potentiometric JC-1 mitochondrial dye and individual BH3 peptides. Results: Mann-Whitney analysis indicates BH3 profiling biomarkers are correlated with response to induction therapy. Among BH3 peptides, BIM was highly significant (p=2X10-6; CI[0.73,0.94]) with a notable sensitivity/specificity profile (AUC=0.84; p=2X10-10). Multivariate analysis indicates improved profiles for BIM + patient age (AUC=0.89; CI[0.81,0.97])and BIM + patient age +cytogenetic status (AUC=0.91; CI[0.83,0.98]). When patients were stratified by cytogenetic status, BIM was significant for both intermediate (p=0.0017; AUC=0.88; CI[0.71,1.04]) and unfavorable (p=0.016; AUC=0.80; CI[0.60,1.00]), demonstrating that the predictive power of the assay is independent of cytogenetics. Conclusions: Here, BH3 profiling predicts patient response to cytarabine-based treatment regimens with accuracies of 90%. Thus, patients may potentially benefit from being given alternate therapies while at the same time spared the toxicities, cost, and time lost associated with a therapy less likely to exhibit response.
Rate of complete hematological response of elderly Ph+ acute lymphoblastic leukemia (ALL) patients by sequential use of nilotinib and imatinib: A GIMEMA protocol LAL 1408.
Authors: Papayannidis Cristina , Piciocchi Alfonso , Vitale Antonella , Iacobucci Ilaria , Soverini Simona , Di Raimondo Francesco , Paolini Stefania , Pizzolo Giovanni , Carella Angelo Michele , Cazzola Mario , Cuneo Antonio , Leoni Pietro , Luppi Mario , Morra Enrica , Specchia Giorgina , Elia Loredana , Foa Robin , Baccarani Michele , Martinelli Giovanni 
Published: March 2020

7025 Background: We have explored if the administration of two TKIs, Nilotinib (NIL) and Imatinib (IM) can improve the results without increasing the toxicity in the elderly Ph+ Acute Lymphoblastic Leukemia (ALL) patients. We investigate the type and number of BCR-ABL kinase domain mutations developing during and after the study. Methods: We have designed a study (ClinicalTrials.gov. NCT01025505) in which patients more than 60 years old or unfit for intensive chemotherapy and SCT where treated with two TKIs, NIL 400 mg twice daily, and IM 300 mg twice daily, alternating for 6 weeks for a minimum of 24 weeks (study core) and indefinitely in case of response. The 6-weeks rotation schedule was respected, irrespectively of temporary discontinuations. The primary end-point was the rate of Disease Free Survival (DFS) at 24 weeks (4 courses of treatment); the secondary end points included the evaluation of CHR, CCgR and CMR rates. Results: 39 patients have been enrolled in 15 Italian hematologic Centers (median age 66 years, range 28-84). Among these, 8 patients were unfit for standard chemotherapy or SCT (median age 50 years, range 28-59). 27 patients were p190, 5 were p210 and 7 were p190/p210. After 6 weeks of treatment, 36 patients were evaluable for response: 34 were in CHR (94%) and 2 in PHR (6%). 23 patients have already completed the study core (24 weeks), 87% were in CHR and 17 are currently continuing therapy in the protocol extension phase. Thus, the OS at 1 year is 79%, and 64% at 2 years. Overall, 1 patient was primarily resistant and 13 patients have relapsed, with a median time to relapse of 7.6 months (range 0.8-16.1 months), for a DFS of 51.3% at 12 months. Conclusions: In this small cohort of Ph+ ALL elderly/unfit patients, the rates of relapse and progression were not likely to be different from the rates observed with Imatinib alone. Acknowledgements: ELN, AIL, AIRC, PRIN. Clinical trial information: NCT01025505.
Use of Axl, a therapeutic target in AML, to mediate stroma-induced chemoresistance.
Authors: Ben Batalla Isabel , Schultze Alexander , Wroblewski Mark , Erdmann Robert , Heuser Michael , Riecken Kristoffer , Binder Mascha , Cubas-Cordova Miguel , Melanie Janning , Wellbrock Jasmin , Fehse Boris , Hagel Christian , Krauter Jürgen , Lorens James B. , Ganser Arnold , Fiedler Walter M. , Carmeliet Peter , Pantel Klaus , Bokemeyer Carsten , Loges Sonja 
Published: March 2020

7027 Background: Axl, the receptor for Growth Arrest-specific protein 6 (Gas6) plays a role in AML pathobiology (Blood Suppl. Nov 2011; 118: 940). Here, we investigated whether Axl represents a therapeutic target in AML. Methods: Gas6 levels were measured by ELISA and immunohistochemistry. Axl expression was detected by flow cytometry. Co-cultures of (murine) BM stroma cells (primary, OP9, S17) with Mv4-11 and OCI-AML5 cell lines were performed. Results: We found (i) higher expression of Axl in AML BM compared to healthy BM donors (66.20 ± 10.87 vs. 0.65 ± 0.10 %; n=8/6; p<0.05); (ii) Axl expression by 68 ± 31% of AML blasts and (iv) higher expression of Axl by CD34+CD38- AML stem cells compared to healthy CD34+CD38- BM stem cells (58.43 ± 4.63 % vs. 6.00 ± 2.01 %; n=7/6; p<0.05). The Axl inhibitor BGB324 dose-dependently inhibited proliferation of primary AML cells with a mean IC50 of 1.8 µM. Sensitivity to BGB324 (i.e. a lower IC50) correlated with Axl expression on leukemia cells (Pearson’s r = -0.9656, p<0.05). Combination therapy with BGB324 and cytarabine exerted an additive therapeutic effect and BGB324 could chemosensitize cytarabine-resistant AML cells. Analyses of BM sections revealed that Gas6 expression was low in AML cells, similar to healthy hematopoietic cells while it was abundantly expressed in AML BM stromal cells with fibroblastic/mesenchymal morphology (BMDSCs). Gas6 expression was considerably lower in control BMDSCs (86 ± 14 % vs. 20 ± 20 %; n=5/7; p<0.05) thus suggesting a possible paracrine interaction between AML cells and BMDSCs leading to Gas6 upregulation in the stroma compartment. Co-culture experiments indicated specific upregulation of murine (m)Gas6 in BMDSCs via leukemia-cell derived IL-10 and M-CSF. This stroma-derived Gas6 could mediate chemoresistance of AML cells in co-culture, which was abrogated by sAxl or by BGB324. Thus, interaction between stroma-derived Gas6 and Axl+leukemia cells forms a chemoprotective niche for leukemia cells. In line with these findings Axl blockade chemosensitizes Mv4-11 cells for treatment with doxorubicine in vivo. Conclusions: Axl represents a therapeutic target in AML and Axl inhibition by BGB324 holds potential to treat chemosensitive and chemoresistant AML.
Activity and tolerability of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk, as a single agent in patients with advanced hematologic malignancies.
Authors: Frankel Arthur E. , Konopleva Marina , Hogge Donna , Rizzieri David , Brooks Christopher , Cirrito Thomas , Kornblau Steven Mitchell , Borthakur Gautam , Bivins Carol , Garcia-Manero Guillermo , Ravandi Farhad , Kadia Tapan M. , Andreeff Michael , Cortes Jorge E. , Hoberman Kenneth , Szarek Michael , Bergstein Ivan , Kantarjian Hagop M. , Rowinsky Eric K. 
Published: March 2020

7029^ Background: SL-401 is a novel biologic targeted therapy directed to the interleukin-3 receptor (IL-3R). IL-3R is overexpressed on cancer stem cells (CSCs) and tumor bulk relative to normal hematopoietic cells in a wide range of hematologic malignancies including AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Since SL-401 targets both leukemia blasts and CSCs, tumor regression and improvement in long-term outcome is expected. The clinical activity and side effect profile of SL-401 were evaluated in a multicenter Phase I/II trial of patients with advanced hematologic cancers. Methods: Eighty-one patients with advanced hematologic cancers, including relapsed or refractory AML (n = 59) and heavily pretreated BPDCN (n = 4), have been enrolled. Patients received a single cycle of SL-401 via 15-minute IV infusion to determine the maximum tolerated dose (MTD) and assess antitumor activity. Results: A single cycle of SL-401 demonstrated single agent activity in relapsed or refractory AML patients, including 2 durable CRs of 8 and 25+ months duration and multiple cases of blast reductions. SL-401, when delivered at therapeutically relevant doses, was associated with > 3-fold greater median overall survival (OS) in AML patients who received 2+ prior lines of treatment relative to historical results. In addition, 3 heavily pre-treated patients with BPDCN, an uncommon malignancy that expresses high levels of IL-3R and is ultrasensitive to SL-401 (IC50 values in the femtomolar [10-15 M] range), had CRs, with durations of 5, 3+ and 1+ months. The MTD was 16.6 µg/kg/day; the dose-limiting toxicities of hypoalbuminemia and edema, which are manifestations of capillary leak, occurred at 22.1 µg/kg/day. Other ≥ Grade 3 adverse events included transient transaminase elevations. There was no treatment-related myelosuppression. Conclusions: SL-401 was well tolerated and demonstrated single agent activity in patients with relapsed or refractory AML and BPDCN. Based on these findings, single agent SL-401 given in multiple cycles will be advanced into pivotal studies of AML (3rd-line) and BPDCN. Clinical trial information: NCT00397579.
Phase II study of orally administered rigosertib (ON 01910.Na) in transfusion-dependent lower-risk myelodysplastic syndrome (MDS) patients.
Authors: Raza Azra , Mukherjee Siddhartha , Eisenberger Andrew , Mears J. Gregory , Wilhelm Francois 
Published: March 2020

7031 Background: Rigosertib, a novel small molecule inhibitor of PI3-Kinase and PLK pathways is currently evaluated (IV infusions) in a phase III trial in higher risk MDS patients who have failed hypomethylating agents. A previous phase I study found good bioavailability and activity of orally administered rigosertib in transfusion-dependent MDS patients (ASH 2011). Here we report preliminary results from an ongoing phase II study. Methods: This is a randomized, two-arm study of oral rigosertib (560 mg bid) administered either intermittently (2 out of 3 weeks) or continuously. Transfusion-dependent patients must have received at least 4 units RBC transfusions over 8 weeks before randomization, and can receive transfusions and erythrocyte stimulating agents (ESAs) while on study. Results: Twenty nine MDS patients (25 intermediate-1 and 4 low risk per IPSS classification) have been randomized as of December 17, 2012. Overall oral rigosertib was well tolerated except for a high incidence (5 of 9 patients) of grade 2+ urinary side effects (dysuria, hematuria, cystitis, and urinary urgency), in the continuous dosing arm. Accordingly, the protocol was amended to allow all patients to be treated with intermittent dosing, with option of dose interruption/reduction resulting in a much lower frequency of urinary side effects (4/20 patients with urinary grade 2+ toxicity). Fifteen patients (none of them with del5q cytogenetic) have been treated with intermittent dosing for at least 8 weeks. Seven (47%) patients achieved transfusion independence (no RBC transfusion for at least 8 consecutive weeks), which lasted 8 to 27 + weeks. Six of 7 responding patients were refractory to prior treatment with ESAs and 5 of these 7 patients received concomitant ESAs, suggesting an effect of rigosertib on ESA resistance. Conclusions: Preliminary results of this phase II study indicate that intermittent dosing of rigosertib administered orally is well tolerated and active in producing transfusion independence in approximately 50% transfusion dependent, lower risk MDS patients. The contributing role of rigosertib and ESAs in these transfusion responses is being investigated. Clinical trial information: NCT01584531.
Cutaneous complications in hematopoietic cell transplant recipients: Impact of biopsy on patient management.
Authors: Paun Oana Valeria , Phillips Tycel Jovelle , Fu PingFu , Novoa Robert , Honda Kord , Lu Kurt Quoc , Lazarus Hillard M. 
Published: March 2020

7036 Background: Although skin biopsies are recommended for diagnostic purposes in hematopoietic cell transplant (HCT) recipients, their utility in directing management of post transplant cutaneous eruptions remains uncertain. Little evidence was found in support of this procedure either from a diagnostic or prognostic perspective. Methods: We retrospectively evaluated 351 consecutive HCT recipients transplanted at our institution between January 2005 and December 2011; 156 patients underwent 388 cutaneous biopsies. Results: The group that underwent cutaneous biopsy after transplantation and the group that was spared the procedure were homogenous with regards to age and gender. The pre-biopsy diagnosis and final diagnosis differed in 213 episodes (55%) as determined by histologic evaluation. Biopsy results led to a change in therapy in 61 of 388 (16%) biopsied rashes. With regards to therapy changes, 24 of 61 (39%) occurred in response to a clinical diagnosis of GVHD. In this situation the most frequently noted change was augmentation or addition of systemic immuno-suppression (19 of 24). Changes in systemic therapy occurred with similar frequencies with respect to concordance or discordance between clinical and histopathologic diagnosis (p = 0.12). We used classification and regression tree analysis to develop an algorithm to predict the biopsy yield as expressed by change of management. This is a non-parametric decision tree learning technique that produces a classification tree based on a categorical dependent variable, formed by a collection of rules based on variables in the modeling data set. Conclusions: Cutaneous biopsy findings often changed the clinical dermatologic diagnoses of HCT recipients; however, the impact of biopsy results on treatment decisions was less profound; altered diagnoses in patients who underwent biopsy often did not lead to therapy changes. Skin biopsies of post-transplant patients may not be mandatory for either diagnostic or therapeutic reasons, but in carefully chosen circumstances can yield extremely important data. A prospective study should be undertaken in order to evaluate current practice data and to validate our decision making analysis tree.
Impact of oral mucositis on outcomes of multiple myeloma patients treated with high-dose melphalan conditioning and autologous stem cell transplantation (ASCT).
Authors: Jaguar Graziella Chagas , Rodrigues Gustavo Henrique , Guollo Andre , Camandoni Vanessa Oliveira , Melo Leila Maria Magalhães Pessoa , Alves Fabio Abreu , Lima Vladmir Claudio Cordeiro 
Published: March 2020

7037 Background: High-dose melphalan is the standard conditioning regimen for patients with multiple myeloma (MM) undergoing ASCT. However, this therapy is commonly associated with severe oral mucositis (OM). Low-level laser therapy (LLLT) has been reported as an effective method in preventing this complication. The aim of this study was to define the potential impact of OM on outcomes in patients with MM undergoing ASCT and receiving preventive LLLT. Methods: We describe a retrospective cohort of 79 consecutive patients with MM who received high-dose melphalan conditioning. All patients received prophylactic LLLT application performed daily from the beginning of the conditioning regimen up to day +2. The patients continued receiving LLLT in case of OM grade ≥ 2 until complete remission of the lesions. OM severity was assessed daily using WHO scale from the beginning of conditioning until hospital discharge. We examined the relationship between worst OM grade and clinical outcomes, including days with oral pain, days of total parenteral nutrition, days of LLLT and days with neutropenic fever. Results: Of 79 patients, 55 (69.62%) experienced OM grade 0-1, 16 (20.25%) experienced OM grade 2, 7 (8.86%) grade 3 and 1 (1.26%) grade 4. Patients with OM grade 0-2 had statistically fewer days of oral pain compared with grade 3-4 (0.88 and 6.25 days, respectively, p = 0.0001). The worst OM grade was also significantly (p < 0.05) associated with days of narcotic therapy and length of LLLT. Severe OM was not associated with febrile days or the use of parenteral nutrition. Conclusions: Severe OM is associated with worse clinical outcomes. In this transplantation setting, severe OM was not common as previously reported in literature, probably due to LLLT. Controlled randomized trials should be performed to confirm the real benefit of LLLT in this scenario as well as the pharmacogenomics and pharmacokinetic studies to better understand interpatient variability of melphalan exposure and toxicity.