bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes following induction chemotherapy in patients with AML arising from MDS: Analysis of prognostic factors
Authors: Bello C. M. , Yu D. , Zhu W. , Wetzstein G. A. , Lancet J. E. 
Published: August 2020

7088 Background: Secondary acute myeloid leukemia (sAML) arising from myelodysplasia (MDS) or a myeloproliferative neoplasm (MPN) has a poor prognosis. To date, there is limited knowledge about risk factors that determine how sAML will respond to treatment. This analysis evaluated possible prognostic factors in patients with sAML that were treated with anthracycline-based induction therapy. Methods: Retrospective chart review of patients with untreated AML from MDS/MPN treated with standard induction therapy from January 2004 to September 2008. Age, IPSS, ECOG PS, cytogenetics, duration of MDS, and prior MDS treatment were evaluated for their impact on obtaining complete remission (CR) or CR with low platelets (CRp) and overall survival (OS). Results: Sixty-one patients with sAML who received induction therapy were evaluated: median age (range) = 66 (36–82) years; M = 67%, ECOG PS 0 or 1 = 86%; poor-risk (PR) cytogenetics = 33%; IPSS > 1 = 43%; prior therapy for MDS with decitabine or azacitidine (DM) or lenalidomide (L) = 41% (25 pts). Of the entire group, 59% (36 pts) achieved CR/CRp (95% CI: 46%-71%) and the median OS was 6.5 (95% CI: 3.9–8.1) mo. Multivariable analysis indicated that the same three factors were significantly negatively associated with CR/CRp as well as OS: PR cytogenetics, prior treatment with DM/L, and long transformation to AML on log scale. Only 32% of the group that received prior treatment with a DM/L achieved CR/CRp compared to 78% in non DM/L-treated patients (OR = 0.13, 95% CI: 0.04–0.42). The CR/CRp rate for those with intermediate risk (IR) cytogenetics was 70% compared to only 35% for those with PR cytogenetics (OR = 4.33, 95% CI: 1.38–13.6). Those with PR cytogenetics had a median OS of 2.8 mo compared to 7.5 mo for IR (p = 0.01). The median OS for those treated with a DM/L was 3.7 mo compared to 10.5 mo for non DM/L-treated patients (p < 0.0001). Conclusions: Prior MDS treatment with a DM/L, PR cytogenetics and long transformation to AML are independent negative prognostic factors for response and OS in patients with sAML following induction therapy, suggesting that such patients may be better served by novel approaches, and that stratification for these risk factors should be considered in future clinical trials. Larger-scale confirmation of these data is ongoing. No significant financial relationships to disclose.
Feasibility of hypomethylating therapy in patients with renal insufficiency
Authors: Batty G. , Kantarjian H. , Issa J. J. , Garcia-Manero G. , Pierce S. , O'Brien S. , Jabbour E. , Cortes J. , Ravandi F. 
Published: August 2020

7089 Background: Epigenetic therapy with hypomethylating agents (HA) is the standard of care in patients (pts) with myelodysplastic syndrome (MDS). Although neither 5-azacytidine (5AZA) nor 2'-deoxy azacytidine (decitabine; DAC) are excreted by the kidneys, many studies exclude pts with a serum creatinine level (sCr) ≥ 1.5 mg/dL. Moreover, there are no reports of use of these agents in pts with renal insufficiency (RI) commonly seen in pts with MDS. Methods: We investigated the outcomes of pts with RI and MDS, chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) receiving therapy with HA. RI was defined by a sCr ≥ 1.5 mg/dL. We examined the compliance, dose adjustments (DA), and complications of treatment with DAC and 5AZA given at standard doses. We used the International Working Group criteria to evaluate the response rates. Data for pts with sCr > 2 mg/dL were compared to pts with sCr ≤ 2 mg/dL (Kantarjian H, et al, Blood. 2007). Results: Forty-two pts with sCr ≥ 1.5 mg/dL (including 17 with MDS, 16 with AML, and 9 with CMML) were treated with DAC or 5AZA alone or in combination with other agents (primarily histone deacetylase inhibitors). 14 (33%) and 28 (67%) of the pts received 5AZA and DAC, respectively. The median number of courses was 4.5 (range 1–19). 9 pts (21%) required treatment delay or discontinuation, and 12 pts (28%) required dose reduction (DR). Overall, 25 (62%) had an objective response (OR), and 4 pts (9%) had complete response (CR). 15 (36%) and 7 (17%) of the pts experienced episodes of therapy-related infections and bleeding, respectively. Among 12 pts who had sCr > 2.0 mg/dL, 7 pts (58%) required DR due to myelosuppression (n = 3) and to worsening of renal function (n = 4). The incidence of complications, DA, and the response rate were not significantly different for pts with sCr > 2.0 mg/dL. Conclusions: The use of HA is well tolerated in pts with MDS and AML and RI who achieved comparable OR rates to those without RI. Dose adjustment might be required in some pts. [Table: see text] [Table: see text]
Patients with secondary myelodysplastic syndromes (MDS) who are enrolled in AVIDA, a longitudinal registry for patients receiving azacitidine (AZA)
Authors: Grinblatt D. L. , Narang M. , Malone J. M. , Sweet D. A. , Dunne T. S. , Sullivan K. A. 
Published: August 2020

7094 Background: Prevalence of secondary MDS (sMDS) is increasing because of improved survival of patients treated with chemotherapy or radiotherapy and aging of the population. Methylation of cell cycle regulators is common in sMDS, thus the hypomethylating agent AZA may have a role in the treatment of these patients. AVIDA is a longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of patients receiving AZA. AVIDA patients with sMDS were investigated and compared with registry patients with primary MDS (pMDS). Methods: Baseline demographics and disease characteristics were obtained at enrollment. Transfusion requirements and onset of transfusion independence were recorded. Transfusion independence was defined as no transfusions for at least 56 days. The first day of the 56-day period with no transfusions was noted as the time at which patients first achieved transfusion independence. Results: As of October 8, 2008, 23 patients with sMDS due to exposure to radioiodine (18), benzene (2), radiation (1), or other (2) have received AZA. Median time since diagnosis was 1 month versus 4 months for pMDS patients (n = 203). At baseline, patients with sMDS had a similar median age (71 yrs) compared with pMDS patients (75 yrs). However, a higher proportion of patients with sMDS had a poor-risk karyotype (44% vs. 11%), 2 to 3 cytopenias (78% vs. 52%), and an International Prognostic Scoring System (IPSS) risk score of intermediate-2/high (57% vs. 23%) compared with pMDS patients. Patients with sMDS have received 93 cycles of AZA, and as of this analysis, have received a median of 4 cycles (range, 1–13). Most common dose and schedule was 75 mg/m2 (81%), 7 days on treatment (39%) for patients with sMDS vs 75 mg/m2 (88%), 5 days on (47%) for pMDS patients. Six of 15 (40%) sMDS patients with ≥ 56 days treatment duration had received a red blood cell (RBC) transfusion during the 6 months prior to AVIDA. Of these patients, 4/6 (67%) have achieved RBC transfusion independence. Conclusions: Patients with sMDS are being treated with AZA in the community-based setting with early data demonstrating substantial benefit in transfusion independence. [Table: see text]
Exploratory analysis describing ultrasonic (US) evaluation of spleen size during peripheral blood progenitor cell (PBPC) mobilization by filgrastim in normal donors
Authors: Stiff P. J. , Hansen K. S. , Dreiling L. , Guo M. , Artz A. S. 
Published: August 2020

7102 Background: Filgrastim is used to mobilize CD34+ cells into the peripheral blood that are collected by apheresis for allogeneic transplantation. We prospectively evaluated spleen size during PBPC mobilization Methods: Donors ≥18 yrs eligible to be PBPC donors per institutional guidelines enrolled. Splenic assessments were done before, during, and after PBPC mobilization. Filgrastim dose and schedule and leukapheresis (LK) procedures were per local practice. Spleen size by US was measured in 3 dimensions: longitudinal (craniocaudal), transverse, and diagonal (perpendicular to transverse). Splenic volume was estimated by taking the cross-product of 3 dimensions and multiplying by 0.52, approximating an ellipse volume. Stiff (ASH 2007) reported the primary endpoint, fold change from baseline in splenic volume during mobilization. Exploratory analyses, including a linear regression evaluating the effect of age and baseline spleen size on fold-change, were performed. Results: 309 enrolled, median age 44yrs, 56% male. Median fold volume change from baseline to first LK was 1.47, resolving to near baseline 1 week after last LK. No significant clinical sequelae, including splenic rupture, were reported. Older donors appeared to have the smallest baseline spleen volume and the largest fold change (table). Linear regression analyses indicated age was a significant predictor for both baseline spleen volume (p=0.0031) and spleen volume fold change from baseline at first LK (p=0.0499). Conclusions: During mobilization, spleen volume transiently increased from baseline to day of 1st LK and returned to near baseline 1 week after last LK. Older donors tended to have smaller baseline splenic volume and greater fold changes in spleen size. Preclinical models suggest decreasing hematopoietic stem cell homing after mobilization with aging (Morrison 1996; Wagers 2002), which could result in splenic accumulation of progenitor and stem cells. [Table: see text] [Table: see text]
Effects of glucocorticoid treatment on the functional capacity of stem cell transplant recipients entering a rehabilitation program
Authors: Scheetz J. S. , Morris G. S. , Brueilly K. E. , Brannan E. A. , Del Fabbro E. 
Published: August 2020

7104 Background: Emerging data strongly supports the concept that stem cell transplant (SCT) recipients derive psychological and physiological benefit from participation in exercise training programs. Many SCT recipients receive glucocorticoids (GC) for prolonged periods, increasing their risk for proximal muscle damage and raising the possibility that SCT recipients on GC may differ from those SCT recipients not receiving GC in terms of their exercise/functional capacity. This becomes an important reconditioning issue because exercise prescription and progression is predicated on initial exercise capacity. Therefore the purpose of this study was to compare the initial functional capacity of outpatient STC recipients receiving GC to STC recipients not receiving GC. Methods: The medical records of 163 successive SCT recipients referred to Rehabilitation Services for reconditioning were retrospectively reviewed for demographic information and measures of exercise/functional capacity (6-min walk test, 50-ft fast walk, and repeated sit-to-stand times) collected at the initial physical therapy visit. Data from SCT recipients on GC (ON) were compared with that of SCT recipients not on GC (OFF) by means of an unpaired t-test (α=0.05). Data are presented as mean + standard deviation. Results: Demographic and functional measures are presented in the following tables. Significant differences between group means are denoted by an asterisk. Conclusions: STC recipients on steroids have comparable endurance capacity to those STC recipients not on steroids, but are less capable of performing lower extremity activities requiring rapid movement and receive rehabilitation services later in the post transplant recovery course. These results suggest rehabilitation strategies are 1) needed for STC patients, 2) should be individualized according to the patient's drug regime, and 3) should be initiated soon after the stem cell transplant. [Table: see text] No significant financial relationships to disclose.
Phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small cell lung cancer: CALGB 30407
Authors: Govindan R. , Bogart J. , Wang X. , Hodgson L. , Kratzke R. , Vokes E. E. 
Published: August 2020

7505 Background: Cisplatin, etoposide and concurrent thoracic radiation has remained the standard treatment for locally advanced unresectable non small cell lung cancer (NSCLC) over the past two decades. The Cancer and Leukemia Group B (CALGB) conducted a phase II study using a novel chemotherapy regimen administered in systemically active doses with thoracic radiation (CALGB 30407). We previously reported the preliminary safety results (ASCO 2008, abstract 7518). Methods: Eligible patients with previously untreated stage III NSCLC received thoracic radiation (70 Gy) along with carboplatin (AUC 5) and pemetrexed 500 mg/m2 on day 1 administered intravenously every 21 days for 4 cycles (arm A) or the same chemotherapy regimen with weekly cetuximab for 6 weeks concurrent with radiation (arm B). All patients received four additional cycles of pemetrexed (500 mg/m2 every 21 days) as consolidation therapy. The primary endpoint was the percentage of patients who lived longer than 18 months after starting initial treatment. We planned to study the regimen (s) further if the 18 month survival rates equaled or exceeded 55%. Results: Characteristics of the 99 eligible pts (48 in arm A and 51 arm B) enrolled from 09/05 to 1/08: male 62%, 22% were 70 yrs or older. The most common histological type was adenocarcinoma (46% in Arm A and 41% in Arm B). Updated toxicity data (grade 3 or greater, %) by arms (arm A/arm B) for 106 pts: neutropenia 40/47; febrile neutropenia 8/6, thrombocytopenia 36/34, nausea/vomiting 8/10, esophagitis 32/24, skin rash 2/21 and fatigue 22/17. The median follow up time is 17 months. Preliminary efficacy data by arms (arm A/arm B) for 99 pts: complete or partial response 73% (95% CI 59–83)/71% (95% CI 57–81%), median failure free survival (months) 12.9 (95% CI 8.6–18.0)/10.3 (95% CI 8.7–18.9); 18 month survival 57% (95% CI 41–79)/47% (95% CI 33–67) and median survival (months) 22.3/18.7. Conclusions: The combination of pemetrexed, carboplatin and thoracic radiation has met the protocol-specified criteria for further study. Although it does not appear that the addition of cetuximab confers additional benefit in this setting, further follow-up is necessary. [Table: see text]
Phase II feasibility trial of induction chemotherapy (ICT) followed by extrapleural pneumonectomy (EPP) and postoperative radiotherapy (PORT) for cT3N1M0 or less malignant pleural mesothelioma (MPM) (EORTC 08031)
Authors: Van Schil P. E. , Baas P. , Gaafar R. , Maat A. P. , van de Pol M. , Hasan B. , Klomp H. M. , Abdelrahman A. M. , Welch J. , Van Meerbeeck J. 
Published: August 2020

7509 Background: MPM is a highly lethal disease and the role of EPP in the treatment of early stage, potentially resectable MPM remains controversial. EORTC 08031 phase II trial investigated the feasibility of trimodality therapy (TMT) consisting of ICT followed by EPP and PORT. Methods: Eligibility criteria were cT3N1M0 or less, proven MPM, < 70 years, PS 0–1, fit for TMT. ICT consisted of 3 courses of cisplatin 75mg/m2 and pemetrexed 500mg/m2 q3weeks. Non-progressing patients (pts) underwent EPP followed by PORT (54Gy, 30 fractions). Primary endpoint was “success of treatment” defined as a patient receiving the full protocol treatment, still alive 90 days after end of treatment without progression and without grade (G) 3–4 toxicity. Using a one step Fleming design 52 patients and 26 successes were required. Secondary endpoints were toxicity of TMT, overall and progression-free survival. Results: 59 pts were registered between 07/26/05 and 08/24/07, 1 was ineligible. Median age was 57 years (range 26–67), M/F 46/12, all proven MPM (31 epithelial, 18 mixed, 9 other). All pts underwent mediastinoscopy, cT1/T2/T3: 36/16/6, cN0/N1: 57/1. 55 pts received 3 cycles of ICT. G3–4 toxicity related to ICT was rare. 46 pts (79%) were operated, 42 (74%) had EPP. R0/1/2: 30/10/3, 6 were re-operated, pT0/1/2/3/4: 2/5/19/15/4, pN0/1/2/3: 34/2/6/2, 90-day mortality: 3 pts (6.5%); in 38 pts (83%) postoperative complications occurred. PORT was initiated in 38 pts and completed in 37 (65%). After PORT 2 pts (3.5%) died due to infection. Persisting G3/4 toxicity after 90 days: 3 pts (5.3%) due to radiation pneumonitis and bronchopleural fistula. After median follow- up of 19.3 months (mos) median overall survival time was 18.4 mos (95% CI 14.8-NR) and median progression-free survival was 13.9 mos (95% CI 10.9–17.1). Only 24 pts (42%) met the definition of success (one-sided 90% CI 0.36–1.00). Conclusions: EORTC 08031 investigated the feasibility of TMT in pts with proven MPM. Due to the low proportion of “successes” this TMT is not considered to be feasible. Although overall results were similar to other series, adjustments to this TMT are necessary. No significant financial relationships to disclose.
Integration of mRNA and microRNA profiles as prognostic and predictive markers in lung adenocarcinoma
Authors: Strickler J. H. , Mostertz W. , Kim W. , Walters K. , Stevenson M. , Acharya C. , Onaitis M. , Nevins J. , Potti A. 
Published: August 2020

7522 Background: Lung adenocarcinoma (ADC) is a distinct biologic entity with unique gene amplifications (Weir B, Nature 2008). Yet, comprehensive transcriptomic analysis, including microRNAs, specific to lung ADC are lacking. Methods: Using mRNA expression data from a discovery cohort of 154 patients with histologically proven early stage (I and II) lung ADC, signatures of oncogenic pathway and tumor microenvironment status were applied and further organized by hierarchical clustering to develop a metagene model. Further, using in vitro assays in a large cohort of lung ADC cell lines (n = 42) with corresponding mRNA and microRNA data, novel microRNAs associated with a poor prognosis and their relationship to cisplatin resistance was elucidated. Results: In the discovery cohort of 154 patients with early stage disease, activation of oncogenic pathways associated with wound healing (angiogenesis), chromosomal instability, and STAT signaling were associated with an increased risk of recurrence (p<0.001). Utilizing the extremes of survival to identify cohorts of patients as high and low risk phenotypes, using bayesian regression, a 100 gene signature (‘metagene') that captured the diversity of signaling pathways unique to patients at increased risk of recurrence was identified and validated in an independent cohort (n = 364) of lung ADC samples with 78.3% accuracy. Kaplan Meier survival analysis and multivariate analysis further confirmed the independent prognostic value of the 100 gene signature (p= 0.007). Using in vitro cell proliferation assays, predicted high risk lung ADC cell lines were identified as being more resistant to cisplatin therapy than those predicted to be low risk (p=0.001). In a novel manner, we also identified several microRNAs (miR-215, miR-98, miR- 643, let-7b, miR-665, miR-629) associated with a high risk of recurrence and more importantly cisplatin resistance. Conclusions: mRNA and microRNA profiles reflect unique aspects of individual tumors and may characterize histology-specific tumor heterogeneity in lung ADC, providing an opportunity to better characterize the oncogenic process and refine therapeutic options. No significant financial relationships to disclose.
Evaluation of class III beta-tubulin (bTubIII) expression as a prognostic marker in patients with resectable non-small cell lung cancer (NSCLC) treated by perioperative chemotherapy (CT) in the phase III trial IFCT-0002
Authors: Zalcman G. , Levallet G. , Bergot E. , Antoine M. , Creveuil C. , Brambilla E. , Dumontet C. , Morin F. , Depierre A. , Milleron B. 
Published: August 2020

7526 Background: IFCT-0002 phase III trial compared two timings of CT in early lung cancer, all before surgery (PRE) versus PERIoperative, and two CT regimens, CDDP-Gem vs. CBDCA-Pac. 528 patients were randomized. Paraffin embedded post- chemo pathological specimens were collected in the 490 non complete responder patients for tissue expression of the putative biomarker beta-tubulin III (bTubIII). Methods: 423 surgical pathological specimens with enough remaining viable tumor tissue after neoadjuvant chemo were processed for immunohistochemistry as published in the Bio-IALT study. A semi-quantitative score was attributed taking account the number of stained cells and the intensity of staining. Semi-quantitative scores were studied as continuous variables, without any pre- determined cut-off. Multivariate analysis for progression-free (PFS) and overall survival (OS) were corrected with Bonferroni-Holm method for multiple analyses. Median follow-up was 42 months. Results: bTubIII was the only IHC marker significantly associated with poor PFS in univariate (p=0.014) or multivariate analysis, adjusted for histology, T and stage (HR= 1.50 [1.07–2.10]; p=0.020). In patients with a pathological specimen showing a bTubIII positive immunostaining, median PFS was 30.6 months, versus 60.1 months (HR=1.46 [1.08–1.99]) for bTubIII negative patients. bTubIII IHC score remained predictive of poor OS in univariate (p= 0.0065) as in multivariate analysis (p=0.019 with Bonferroni correction, HR=1.75 [1.15–2.68] ). Median OS was not reached for bTubIII negative patients whereas it was 71.7 months in patients with bTubIII immunostaining of any intensity score (HR=1.61, [1.11–2.35]). Conclusions: This study showed a dramatic negative prognostic impact for bTubIII immunostaining in resectable early lung cancer. A subset of bTubIII expressing patients with poor prognosis did not take any advantage from perioperative chemo. Hence, those patients could rather have beneficiated from personalized adjuvant treatment with alternative approaches. No significant financial relationships to disclose.