bluuebunny/crossref_metadata_2025_split huggingface dataset:
Affording Immune Checkpoint Inhibitors (ICI) in the treatment of advanced non-small cell lung cancer (NSCLC): Argentinean National Cancer Institute (ANCI) perspective.
Authors: Gabay Carolina , Pesci Santiago , Caldano Johana , Diaz Maria Celeste 
Published: May 2020

e19404 Background: ICI agents proved clinical effectiveness in metastatic NSCLC; irrespectively PDL1 expression, but they increase costs considerably. Thus its cost-effectiveness (CE) needs to be established in low and middle-income countries. We aimed to assess CE of Pembrolizumab plus carboplatin and pemetrexed (PCP) vs. carboplatin and pemetrexed (CP) in the first-line setting for non-squamous NSCLC, according to PDL1expresion, in Argentinian public healthcare system (APHS). Methods: Clinical outcomes, utilities, and transition probabilities were collected from the available literature (Keynote 189/024) after a systematic review. The certainty of evidence according to GRADE methodology was qualified as high. A Markov model was developed. Model outcomes were measured in quality adjusted-life-years (QALY) and CE was estimated as the incremental cost-effectiveness ratio (ICER) over a 20 years time horizon. Only direct costs were considered from a public price database of the drugs accounted in the model. The WHO ICER threshold, defined as 1-3 GDP per capita, was selected to established CE. Sensitivity analyses were performed to assess the robustness of results. Results: In PDL1≥ 50 % subgroup, PCP increased life expectancy of patients by 1.06 QALY for an incremental cost of USD 71.551 vs. CP with an ICER of 67.352 per QALY. An indirect comparison of PCP vs. Pembolizumab monotherapy found no differences in QALY estimates, however, it was associated with an incremental cost of USD 5.516. QALY estimate for PDL1 1-49% was 0.73 with an ICER of USD 85.984/ QALY gained. PDL1 < 1% obtained a QALY of 0.42 related to the largest ICER (USD 97.095) for the same comparison. The sensitivity analyses using a threshold between 1- 3 Argentinian GDP per capita in 2018 (USD 11.8602) found that PCP has no chance of being considered CE in untreated NSCLC patients. If a 6 GDP threshold is adopted in PDL1≥ 50 %, PCP would have a 50% possibility of being CE. Conclusions: This model was part of the decision-making process in the development of treatment guidelines for metastatic NSCLC in the ANCI. PCP cannot be considered acceptable for the APHS. Strategies to reduce costs are mandatory to improve affordability in our region.
Reducing time to treatment and patient costs with breast cancer: The impact of patient visits.
Authors: Sittenfeld Sarah , Greenberg Zachary , Alhilli Zahraa , Abraham Jame , Moore Halle C. F. , Grobmyer Stephen R. , Monteleone Emily Elizabeth , Tullio Katherine , Shah Chirag 
Published: May 2020

e19407 Background: The purpose of this study was to evaluate the impact of a continuous improvement process aimed at reducing time to treatment on minimizing the number of days spent to complete pre-treatment visits and the associated costs for patients with non-metastatic breast cancer. Methods: System-wide initiatives were implemented in 2015 to minimize time to treatment initiation (TTI), by incorporating lean process strategies and enhanced coordination. Patient and treatment information was obtained through an IRB-approved registry for the years 2015 and 2018. Average number of days spent to complete visits, TTI, and associated patient costs including driving expenses, parking, food, childcare, and lost wages were calculated and compared between the years 2015 and 2018. Results: In 2015, the median TTI was 43.5 days and the average number of separate days spent to attend multidisciplinary visits prior to first treatment was 1.86. These were reduced to 29 days and 1.52 visits, respectively, in 2018 (p < 0.0001 for both). When evaluating treatment visits by surgical procedure, the average number of visits was reduced regardless of surgical procedure. The average number of visits was highest for patients undergoing mastectomy with reconstruction (2.34 in 2015, reduced to 1.65 in 2018, p < 0.0001). A single visit to complete treatment planning was associated with patient costs of $249 as compared with multiple trips costing $491 for 2 visits and up to $1,226 for 5 visits. Conclusions: In breast cancer patients, implementing a continuous improvement process to reduce time to treatment was associated with fewer visits required prior to treatment initiation, resulting in lower patient costs.
Measurements of Mcl-1 protein dependencies using dimerization-specific antibodies as predictive biomarkers for BH-3 mimetic class therapies in AML.
Authors: Cardone Michael H. , Kinloch Andrew , Canakci Mine , Ge Jingping 
Published: May 2020

e19505 Background: The anti-apoptotic Bcl-2 family proteins facilitate pro-survival and resistance to anti-cancer therapies. Measuring the function of these proteins has shown utility in predicting response to treatment. A biomarker platform that assesses the functionality of these proteins by measuring BH3 mediated signaling potential in individual patients’ cancers, could provide a potential guiding platform for treating AML. In AML venetoclax is becoming widely prescribed and highly effective in combination with other drugs. Recent data indicate that Mcl-1 dependence is a resistance factor to venetoclax and that methods for identifying this could provide guidance for combination treatments. We are developing a technology to directly measure the occurrence of heterodimers of Mcl-1, or Bcl-xL, bound to pro-apoptotic BH3-only protein Bim. These measurements are combined in algorithms developed to indicate the cancer cell apoptotic priming state and offer great potential for identifying best AML treatment options. Methods: Monoclonal antibodies against conformation-specific epitopes induced in Mcl-1/Bim and Bcl-xL/Bim protein complexes were made. Selective bonding of Heterodimer Specific Mcl-1 Bim (HSMCB) and Heterodimer Specific Bcl-xL Bim (HSBXB) mabs were confirmed using ELISA, fluorescence polarization, immunofluorescence microscopy and flow, and by immunohistochemistry in genetically defined cell lines and in AML patient biopsied samples. Results: We show that HSMCB signal depends on both Mcl-1 and Bim protein levels while HSBXB requires Bc-xL and Bim levels. The relative signals of HSMCB to unbound Mcl-1 signal ([HsMcB]/[Mcl-1]) provide a biomarker for Mcl-1 dependence. We carefully established binding metrics that correlate to drug response in cell lines. The pharmacological disruption of these complexes is monitored by the ratiometric readouts that serve as predictive biomarkers for BH-3 mimetic drugs in AML cells. Conclusions: Mcl-1 dependence is a predictive biomarker for venetoclax resistance and for response to Mcl-1 targeted therapies. Flow cytometric and IHC based measurements of a heterodimer complex offer a direct and simpler approach that harbors potential for use in clinical settings. Additional antibodies targeting Mcl-1/Bak and Bcl-2/Bim complexes are being tested.
Outcomes of myeloablative, T cell deplete unrelated donor hematopoietic stem cell transplantation at a single center.
Authors: Gaballa Mahmoud , Jang Albert , Hamad Hussein , Bulsara Shaun , Wu Meng-Fen , Carrum George , Ramos Carlos Almeida , Kamble Rammurti , Hill LaQuisa , Pingali Sai Ravi , Vu Ngoc , Scholoff Audrey , Obi Gloria , Heslop Helen E. , Lulla Premal D. 
Published: May 2020

e19525 Background: Myeloablative conditioning (MAC) and unrelated donor (UD) hematopoietic cell transplantation (HCT) are associated with increased non-relapse mortality (NRM) compared with matched related donor (MRD) HCT [18%, 21%, and 32% for MRD, Matched UD (MUD), and mismatched MUD (MMUD), respectively, p < 0.001] (Saber et al, 2012). Our center uses alemtuzumab as means of T cell depletion to mitigate NRM risk in UD HCT. Here, we report outcomes utilizing this strategy. Methods: We retrospectively analyzed adult patients (pts) who received alemtuzumab-based T cell deplete MAC UD HCT from August 2012 to December 2017. Outcomes were estimated via Kaplan Meier and cumulative incidence methods. Results: Sixty-eight pts underwent T cell deplete MAC UD HCT for AML/MDS (n = 32), ALL (n = 18), lymphoma (n = 5), and other diseases (n = 13). Thirty-nine (57.4%) underwent a MUD HCT, while 29 (42.4%) underwent a MMUD (≤ 9/10 match) HCT. Median follow up was 35.5 months (m) (range 1.5 – 71.1). Median age was 46 years (range 21 - 68), 58.8% were male. Nineteen AML pts (67.9% of all AML) were considered high risk defined as secondary AML (n = 3), CR2 or more (n = 9), primary induction failure (n = 6) or having gross residual disease at time of HCT (n = 1). At 24 m, overall survival (OS) for the entire cohort was 65.3% (95%CI (CI) 53.5%- 77.2%), GVHD relapse-free survival (GRFS) was 54.8% (CI 42.8%- 66.9%), NRM was 10.4% (CI 4.5%- 19.2%), and relapse incidence (RI) was 27.3% (CI 17.1%- 38.5%). None of the 68 pts had graft failure or rejection. In the AML/MDS cohort, at 24 m OS was 52.3% (CI 33.9%- 70.7%), GRFS was 41.4% (CI 23.9%- 59%), NRM was 9.7% (CI 2.4%- 23.2%), and RI was 39.1% (CI 21.8%- 56.2%). Non-AML/MDS pts at 24 m had OS, GRFS, NRM and RI of 76.8% (CI 62.6%- 90.9%), 66.7% (CI 51.3%- 82.08%), 11.1% (CI 3.4%- 23.9%), and 16.7% (CI 6.6%- 30.6%), respectively. The table summarizes our outcomes. Conclusions: We show that alemtuzumab-based MAC conditioning for UD HCT has the benefit of being well tolerated with low NRM and high GRFS, while having comparable RI and OS compared to published outcomes of T cell replete MAC UD HCT (Saber et al, 2012). However, the retrospective nature without a comparator is a major limitation which necessitates a future prospective study to validate these findings. [Table: see text]
Intensive chemotherapy in patients with high grade myelodysplastic syndromes (MDS): A systematic review and meta-analysis.
Authors: Benkhadra Raed , Nayfeh Tarek , Bakalov Veli , Hilton Christie , Khan Cyrus , Prokop Larry , Shah Mithun Vinod , Alkhateeb Hassan , Litzow Mark Robert , Murad M. Hassan , Al-Kali Aref 
Published: May 2020

e19530 Background: Intensive chemotherapy (IC) regimens are rarely used in patients with myelodysplastic syndromes (MDS) for many reasons including advanced age at diagnosis, the frailty of these patients, the presence of several comorbidities and potentially increased mortality when such regimens are used. Additionally, very little literature exists on its safety and long-term benefit in this population. Aim: To evaluate the safety and effectiveness of IC regimens in patients with MDS. Methods: We searched MEDLINE, Embase, Scopus and Cochrane databases from each database's inception from 1990 to January 27th, 2020. Keywords include: “MDS”, “induction chemotherapy” and “remission induction”. Studies evaluating different IC regimens with MDS were included. IC studies for patients with relapsed/ refractory MDS were excluded. Studies that combined acute myeloid leukemia (AML) and MDS outcomes were excluded. The random-effects model was used to pool relative risks and incidence rates. Main endpoints were overall remission rates (ORR), 30- and 60-days mortality, 1-year, 2-year and 5-year overall survival (OS). Results: Characteristics: From 2001 records, we included 13 studies [1,164 patients, median age 60.1 years (range, 17-88), males 58.9%, 58.4% patients had abnormal cytogenetics, median bone marrow blasts 17.8% (range 4 -29%), 4 studies were randomized]. Induction outcome: IC regimes included “7+3, FLAG, s-HAM, and few other regimens. Response: ORR was 55%, including 52% CR rate. Safety: 30- and 60-days mortality were 7%, 15%, respectively. Survival outcome: median survival was 11.6 months, 1-year, 2-year and 5-year OS were 48%, 21% and 5%, respectively. Randomized studies comparison: adding growth factors to IC did not show statistically significant effects on outcomes regarding induction mortality, ORR and OS (p-value > .05). Conclusions: IC is rarely used in MDS patients and its use is associated with high mortality rates and low long-term survival. Limitations to our studies include the long span of this review over 3 decades and the difficulty of using published studies that combines MDS and AML patients’ outcome. More studies are needed in this population of interest in the future.
M.D. Anderson experience of immune checkpoint inhibitor therapy in classical Hodgkin lymphoma.
Authors: Nair Ranjit , Pinnix Chelsea Camille , Gunther Jillian Rebecca , Strati Paolo , Westin Jason , Fayad Luis , Hagemeister Fredrick B. , Iyer Swaminathan Padmanabhan , Nastoupil Loretta J. , Parmar Simrit , Rodriguez Maria Alma , Steiner Raphael , Dabaja Bouthaina Shbib , Fang Penny , Flowers Christopher , Noorani Mansoor , Feng Lei , Neelapu Sattva Swarup , Ahmed Sairah , Lee Hun Ju 
Published: May 2020

e20013 Background: Nivolumab and Pembrolizumab are effective immune checkpoint inhibitor (ICI) therapies targeting PD-1/ PDL-1 immune axis. The drugs are currently approved for relapsed/ refractory classical Hodgkin lymphoma (cHL)based on phase I and II trial data. Methods: We conducted a retrospective study of patients (pts) with relapsed refractory cHL treated with ICI therapy at M.D. Anderson Cancer center from 4/2013 to 5/2019 to evaluate the efficacy of this treatment. The responses were assessed using revised response criteria according to the Lugano classification Results: Ninety-two pts treated with nivolumab (66) and pembrolizumab (26) were included. Fifty six pts (63%) were advanced stage at diagnosis, most treated initially with ABVD (88%) and BV-AVD (3%). Seventy percent pts had primary refractory disease or relapsed < 12 months after frontline therapy. At the time of ICI initiation, pts had the following characteristics: median age 35 (range 18-86), extranodal disease - 28 pts (37%), prior BV exposure in 81 pts (89%) with 66% considered BV refractory. Sixty one percent patients were refractory to the last prior line of salvage therapy. Median prior lines of therapy was of 3 (range 1-13) and 53 pts (58%) had a prior HSCT. At a median follow-up time of 20.2 months (range: 1.58 - 55.98 months), median progression free survival was 12.3 months and median overall survival was not reached. Among the 39 patients with no prior transplant, 11 patients who achieved CR with ICI were consolidated with HSCT (autologous - 7 and allogeneic - 4). Of this cohort, 2 pts (1 post auto, 1 post-allo) have relapsed. Five patients in our cohort were treated with an alternative ICI for subsequent relapse; of four patients with response assessment, 3 achieved CR and 1 experienced PD. Conclusions: In this cohort of cHL pts, ICI offered high response rates before and after HSCT supporting the possibility for using ICI earlier in the treatment course for refractory or early relapsed HL.
Risk-adapted therapy for advanced-stage natural killer/T-cell lymphoma: An analysis from the China Lymphoma Collaborative Group Study.
Authors: Liu Weiping , Yang Yong , Qi Shunan , Wang Ying , He Xia , Wu Gang , Qu Baolin , Qian Liting , Zhang Fuquan , Qiao Xueying , Hua Wang , Li Gaofeng , Zhang Yu-Jing , Zhu Yuan , Cao Jianzhong , Wu Junxin , Wu Tao , Zhu Jun , Li Ye-Xiong , Song Yuqin 
Published: May 2020

e20041 Background: Few studies focused on the risk-adapted therapy for advanced-stage natural killer/T-cell lymphoma (NKTCL) due to poor prognosis. Methods: Data of 406 patients with advanced-stage NKTCL from 20 Chinese institutions between 2000 and 2015 were retrospectively analyzed. To develop a prognosis index model for advanced-stage NKTCL, all patients were divided into the primary cohort from South China (n = 198) and the validation cohort from North China (n = 208). Clinical factors related to survival in the primary cohort were identified to construct a new prognosis index model. An external validation for the prognosis index model was performed in the validation cohort. Stratified by the prognosis index model, survival benefit for treatment models was assessed. Results: The median age was 42 years with the ratio of male/female of 2.5:1. Extra-nodal involvement was observed in 72.4% of patients. More than one third of patients received asparaginase (Asp)–containing chemotherapy. In addition, radiotherapy was administrated in 135 (33.3%) patients. The overall response rate (ORR) and complete remission (CR) rate were 59.3% and 38.3% in 337 available patients. The expected 3-year progression-free survival (PFS) and overall survival (OS) rates were 26.9% and 37.3%, respectively. Based on 3 clinical variables including ECOG-PS > 1, elevated LDH and solid organs involvement, a new prognosis index model (ASPRIN) was developed and showed superior discrimination than current models including IPI, KPI and PINK in this particular population. The expected 3-year OS rates in the primary and validation cohort were 54.8% and 52.9% in the low risk group (with 0-1 risk factor), 34.4% and 38.0% in the intermediate risk group (with 2 risk factors), 13.8% and 10.6% in the high risk group (with 3-4 risk factors), respectively. Stratified by ASPRIN model, combined radio-chemotherapy provided better survival benefit than chemotherapy alone regardless of chemotherapy regimens in the low risk group (3-year PFS 52.6% vs. 22.6%, P < 0.001; 3-year OS 72.8% vs. 35.8%, P < 0.001), while Asp–containing chemotherapy improved survival with an increase of about 10%-15% in PFS and OS compared with non–Asp–containing chemotherapy in the intermediate and high risk groups. Conclusions: The outcome of advanced-stage NKTCL is still poor and heterogeneous even in the era of Asp–containing chemotherapy, which highlighted the need of establishing more effective risk-adapted therapeutic strategies.
Circulating nucleosomes in hematological malignancy.
Authors: Terrell Jason , Josseaux Eleonore , Latora Helene , Rommelaere Guillaume , Hardat Natalie , Herzog Marielle , Micallef Jake , Eccleston Mark 
Published: May 2020

e20078 Background: There are over 700,000 new cases of non-Hodgkin lymphoma (NHL), acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL) diagnosed globally each year and approximately 415,000 deaths. The non-specific symptoms of lymphoma and leukemia often delay diagnosis. We investigated the circulating levels of intact nucleosomes containing the histone H3.1 isoform (Nu.Q-H3.1) in a variety of solid tumors, NHL, AML, ALL, and in healthy subjects. Methods: We measured levels of Nu.Q-H3.1 in plasma samples taken from 62 healthy volunteers (mean age = 45 yrs) and 329 patients diagnosed with cancer (mean age = 56 yrs), including 25 patients diagnosed with each of cancer of the bladder, bone, brain, oesophagus, cervix, skin, head & neck or melanoma, 21 patients diagnosed with uterine cancer as well as with NHL (n = 25), AML (n = 25) and ALL (n = 8). The cohort included samples taken from patients at diagnosis and at relapse. Whole blood samples were collected in EDTA plasma tubes, double-centrifuged at 1500 rcf for 15 minutes within 2 hrs of blood draw, after which plasma was transferred to a cryotube and frozen immediately until analysis. Plasma samples (20µl) were analyzed in duplicate for Nu.Q-H3.1 using an ELISA method developed and validated to CLSI guidelines. Results: We observed elevated levels of Nu.Q-H3.1 in the patients diagnosed with various cancers. Only 14 of 271 patients with a solid tumor had levels > 200ng/ml. In contrast the median Nu.Q-H3.1 levels observed for NHL, AML and ALL were 276, 284 and 585ng/ml respectively. The median nucleosome level in 62 healthy subjects was 40ng/ml; the highest level was 198ng/ml. The AUC for all patients diagnosed with NHL, AML or ALL (n = 54) vs healthy volunteers was 91% with a sensitivity of 74% at 95% specificity. The AUC for the subset of patients newly diagnosed with NHL, AML or ALL (n = 31) vs healthy volunteers was 92% with a sensitivity of 81% at 95% specificity. Conclusions: Elevated nucleosome levels have been reported for a number of diseases. Our early results indicate that levels of Nu.Q-H3.1 are particularly elevated in haematological malignancies and may be a useful diagnostic tool warranting further study.
T-cell receptor gene rearrangement clonality, flow cytometry status, and associated outcomes in early-stage CTCL.
Authors: Marks Jennifer Aline , Switchenko Jeffrey M. , Allen Pamela Blair , Lechowicz Mary Jo 
Published: May 2020

e20087 Background: Cutaneous T-Cell Lymphoma (CTCL) is a monoclonal lymphoproliferative disease. Studies hypothesize T-cell receptor gene (TCR) rearrangement and flow cytometry as means of predicting those at risk of aggressive disease. We aimed to assess outcomes in early-stage disease by TCR clonality and flow cytometry in peripheral blood. Methods: We performed a retrospective analysis of 328 pts with early-stage (1-2A) CTCL using our internal CTCL database with protocol approved by our institutional review board (IRB00045798). Early-stage CTCL pts included were those with TCR clonality and/or flow cytometry in the peripheral blood obtained within 6 months of diagnosis and/or at initial check. Overall survival (OS) and time to next treatment (TTNT) were examined. Missing data or OS/ TTNT values larger than 25 years were excluded. Univariate/multivariate models and Kaplan-Meier analyses were run for both OS and TTNT. Results: In the cohort (n = 328) the median age was 53.2 years (8.6-87.5), with equal sex predominance, and distribution among stages. 261 pts had TCR clonality assessed. 78.5% (n = 205) were non-clonal and 21.5% (n = 56) were clonal. 284 pts had flow assessed (n = 44/328 with missing data). 89.8% (255/284) were flow (-), initially. Of those without clonality, 95.29% (n = 182 p < 0.001) were flow (-). 76% (38/56 p < 0.001) with TCR clonality were flow (-). TCR clonality in the blood was not associated with a survival nor TTNT by univariate or multivariate analyses. Age at diagnosis was significant contributing to OS and TTNT in multivariate analyses (HR 1.04,CI 1.01-1.06,p < 0.01;HR 1.01, CI 1.00-1.02,p = 0.033, respectively). Flow cytometry status was not associated with TTNT. Flow cytometry in the blood was associated with survival but was limited to stage 2A pts (n = 98, p = 0.0171). Median survival of those with flow negative results was 20.8 yrs (CI 11.8,NA, p = 0.0171) with a 5-year survival of 95.8%(CI 87.4%-98.6%) compared to those with positive results of 12 yrs (CI 1.3, NA), p = 0.0171) with a 5-yr survival of 80.8%(CI 42.3%-94.9%). Conclusions: We found no difference in OS or TTNT by TCR status in blood for stage 1-2A disease. Flow cytometry status and OS differed in stage 2A pts. Significance of TCR clonality or flow cytometry in early-stage disease remains unclear. Findings raise questions of needing to risk-stratify in early-stage disease by TCR gene rearrangement or flow cytometry. Those with stage 2A disease, flow cytometry status may confer some benefit. Larger cohorts needed to further investigate these findings.