bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional assessment of performance status in patients with myelofibrosis (MF): Utility and feasibility of the 6-minute walk test (6MWT)
Authors: Mesa R. A. , Kantarjian H. , Tefferi A. , Cheville A. , Pardanani A. , Levy R. , Erickson-Viitanen S. , Thomas D. , Cortes J. , Borthakur G. , Verstovsek S. 
Published: August 2020

7083 Background: Patients with Myelofibrosis (MF) suffer from significant fatigue, constitutional symptoms and splenomegaly (Mesa et. al. Cancer 2007) not improved by current therapy. The 6MWT measures functional status in cardio-pulmonary clinical trials. We undertook a prospective feasibility study of the 6MWT in MF patients for use in therapeutic clinical trials. Methods: MF patients (able to walk, normal vitals, not on a JAK2 inhibitor) were eligible. Baseline features and the MF symptom assessment form (MFSAF: Mesa et. al. Blood 2008) was administered. The 6MWT was administered in standardized fashion (American Thoracic Society: observed laps of a 30 - 35 meter long course, indoors, level, without encouragement), and then repeated for further validation. Results: Safety of the 6MWT: Fifty five MF patients were enrolled with only 2 patients (3%) stopping the 6MWT early secondary to fatigue. There were no adverse events attributable to undergoing the 6MWT in test subjects. Results of the 6MWT: Current results of our ongoing study demonstrate compared to age matched healthy volunteer controls, males with MF walk approximately 90 meters less and females with MF walk approximately 60 meters less (Table). Correlation of 6MWT Results to Patient Reported Symptoms (MFSAF): Results from the MFSAF demonstrated the fatigue (as assessed by the brief fatigue inventory (Medoza et. al. Cancer 1999) embedded in the MFSAF) showed patients with a higher BFI (i.e., more fatigued) had more impairment in the 6MWT than those with low BFI scores. Symptomatic burden as assessed by the MFSAF were typical for MF, correlation of individual symptom severity with 6MWT will require a larger trial for adequate power. Conclusions: The 6MWT can be safely performed in un-selected MF patients, and demonstrates a functional deficit compared to published controls. Validation of the ability of the 6MWT to measure functional improvements in MF patients as a response to novel therapy trials is planned. [Table: see text] No significant financial relationships to disclose.
Persistence of complete molecular remission in chronic myeloid leukemia after imatinib discontinuation: Interim analysis of the STIM trial
Authors: Mahon FX F. , Rea D. , Guilhot F. , Legros L. , Guilhot J. , Aton E. , Dulucq S. , Reiffers J. , Rousselot P. 
Published: August 2020

7084 Background: Imatinib (IM) has greatly improved survival in chronic myeloid leukemia (CML). However, IM must be continued for an indefinite period of time. A multicenter trial “Stop Imatinib” (STIM) was initiated in July 2007, in order to evaluate the persistence of complete molecular remission (CMR) after stopping IM and determine factors associated with CMR persistence. Methods: Inclusion criteria were IM treatment duration ≥3 years and sustained CMR, defined as BCR-ABL transcripts below a detection threshold of a 5-log reduction (undetectable by RQ-PCR) for ≥2 years. Molecular relapse was defined as RQ-PCR positivity confirmed on 2 successive occasions. In case of relapse, pts were rechallenged with IM at 400 mg daily. Molecular monitoring was performed according to international recommendations. Results: Sixty-nine pts were recruited among which 60 with a follow-up >1 month, including 22 males and 38 females. Median age was 62 (29–80), 31 pts had been treated with IFN prior to IM and 29 with IM frontline (de novo). Median follow-up was 5 months (1–16). Relapse occurred in 37 pts within 6 months of IM discontinuation. Only 1 pt relapsed after 6 months (M7). All patients in molecular relapse were sensitive to IM reintroduction. At last follow-up in December 2008, CMR was sustained in 8 pts at M14 and 3 pts at M16. No differences in terms of demography, duration of IM treatment and CMR duration were found between pts who relapsed and those who did not. At M9, the probability of persistent CMR was 46% (95% CI: 32–59%), 53% (95% CI: 33–69%) for previously IFN-treated pts and 39% (95% CI: 20–58%) for de novo pts (p = 0.54). A trend for a lower probability of relapse in low Sokal score pts was observed. Conclusions: Our data confirm that CMR can be long-lasting after discontinuation of IM. Using stringent criteria, it is possible to stop IM in patients with sustained CMR, even in those treated with IM as a single agent. Updated follow-up will be presented. No significant financial relationships to disclose.
Treatment patterns of chronic myelogenous leukemia patients with suboptimal responses to imatinib
Authors: Guérin A. , Guo A. , Williams D. , Yu A. P. , Wu E. , Latremouille-Viau D. , Tsaneva M. , Signorovitch J. , Griffin J. D. 
Published: August 2020

7090 Background: Imatinib is the first-line therapy for Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Patients with suboptimal responses may have the dose of imatinib escalated or may be switched to an alternative kinase inhibitor such as dasatinib. The aim of this study is to examine the real-world treatment patterns of imatinib and dasatinib in CML patients. Methods: Two large U.S. administrative claims databases from January 1999 to March 2008 were combined (MarketScan and Ingenix Impact) to extract de-identified information of patients diagnosed with CML (ICD-9 code: 205.1) who were initiated on imatinib. Patients were followed from the first observed imatinib prescription to the end of data availability. Patients who increased imatinib dose to >400 mg/day were defined as dose escalators, while patients who initiated on imatinib and further switched to dasatinib were considered as switchers. Rates of imatinib dose escalation and switching to dasatinib were estimated. Kaplan-Meier (KM) survival analyses were used to estimate the rate of imatinib discontinuation, defined as a lack of imatinib supply for at least 90 days. Among switchers, the rate of switching back to imatinib was also estimated using KM survival analysis. Results: Among the 5,159 CML patients initiated with imatinib, 1,144 patients either had dose escalation of imatinib (839) or were switched to dasatinib (305) during the study period. Of the 5,159 patients, 12.1% patients discontinued imatinib by the end of the first year, and 25.4% discontinued by the end of the third year. Among the 305 switchers, 115 (37.7%) had an imatinib dose increase prior to the switch, and 66 (21.6%) were escalated to 800 mg of imatinib before switching. 51 patients (16.7%) had used imatinib for <6 months before switching, and 17.1% switched back to imatinib within 6 months of dasatinib treatment. Conclusions: This study showed that great variability was observed in the real world treatment pattern of CML patients. Most CML patients who initiated on imatinib did not dose increase or switch during the study period. Of those who switched to dasatinib, most did not attempt to increase the dose before switching, and a sizeable portion of patients had to switch back to imatinib. [Table: see text]
Mortality and hospitalization in myelodysplastic syndromes (MDS) using the SEER-Medicare linked database
Authors: Lindquist K. , Danese M. , Knopf K. , Mikhael J. 
Published: August 2020

7091 Background: Mortality in patients with MDS is high, and most require transfusions, emergency department (ED) visits, and hospitalizations. The relationship between these outcomes with the key complications of MDS (anemia, neutropenia, thrombocytopenia) has not been well studied. Methods: Patients who were ≥ 66 years at MDS diagnosis in 2001 or 2002 were identified from SEER registries. Those with both Medicare Part A and B were followed until death or the end of 2005. Mortality, transfusions, ED visits, and hospitalizations were based on Medicare data. The presence of complications was based on diagnosis codes, transfusions, and medication use. Kaplan-Meier incidence was estimated for each outcome. Factors associated with each outcome were based on multivariable Cox models with baseline age, gender, race, co-morbidity level, socio-economic status indicators, and time-varying covariates for each complication. Results: In 1,863 MDS patients, the 3-month incidence of transfusion, ED and hospitalization was 45%, 41%, and 62%, and 3-year incidence was 75%, 87%, and 91% respectively. Median survival was 22 months. The 3-year incidence of anemia, thrombocytopenia and neutropenia was 89%, 37%, and 15% respectively. See table for multivariate results. Conclusions: Starting shortly after diagnosis, MDS patients have high rates of transfusions, ED visits, and hospitalizations. Diagnoses of anemia, neutropenia, and thrombocytopenia are strongly associated with this utilization. The presence of anemia and thrombocytopenia are important independent risk factors for death. [Table: see text] [Table: see text]
Adverse events associated with escalating imatinib versus switching to dasatinib in patients with chronic myelegenous leukemia
Authors: Wu E. , Guo A. , Williams D. , Guérin A. , Yu A. P. , Latremouille-Viau D. , Tsaneva M. , Signorovitch J. , Griffin J. D. , Bollu V. 
Published: August 2020

7092 Background: After initial therapy with imatinib, some chronic myelegenous leukemia (CML) patients may require dose escalation or switching to another BCR/ABL kinase inhibitor to achieve the desired response. This study compared adverse events associated with either escalation of imatinib or switching to dasatinib. Methods: Two large administrative claims databases were combined (MarketScan and Ingenix Impact) to extract deidentified information on 17,382 patients diagnosed with CML (ICD-9 code: 205.1) from January 1999 to March 2008. 474 patients (dose escalators) had their dose of imatinib increased at some point to >400 mg/day but were never given dasatinib, while 175 patients were switched to dasatinib with or without dose escalation of imatinib (switchers). Patients were followed from the index date to treatment discontinuation or end of eligibility. Cox proportional-hazard models were used to compare the risk of common adverse events (AEs) associated with escalation or switching to dasatinib, controlling for demographics, imatinib treatment patterns, and prior therapies at baseline. Patients with the studied AEs at baseline were excluded from analyses of the corresponding AEs. Results: Switchers experienced significantly higher risk of the following AEs than escalators: fluid retention (HR 3.22 p < 0.0001), pleural effusion (HR 4.90 p < 0.0001), thrombocytopenia (HR 3.25 p = 0.0044), neutropenia (HR 3.40 p = 0.0009), and some non-hematologic adverse events (HR 2.38 p < 0.0001), dyspnea (HR 4.02 p < 0.0001), constipation (HR 5.79 p = 0.0041), nausea and vomiting (HR 2.40 p = 0.0100), and congestive heart failure (HR 5.01 p < 0.0001). No statistically significant differences in risk of other common AEs associated with imatinib and dasatinib were identified. Conclusions: 15.4% of CML patients treated with ≤400mg of imatinib initially either had dose escalation or switch to dasatinib. Significantly more AEs were associated to those who switched to dasatinib than those who dose escalated. Further study is warranted to examine the causality of the difference in these AEs. [Table: see text]
Lymphocyte reconstitution in multiple myeloma patients after allogeneic G-CSF-mobilized hematopoietic progenitor cells transplantation from HLA-identical siblings
Authors: Martino M. , Fedele R. , Irrera G. , Messina G. , Cuzzola M. , Gareffa C. , Console G. , Dattola A. , Iacopino P. 
Published: August 2020

7098 Background: Allogeneic transplantation of G-CSF-mobilized hematopoietic progenitor cells (HPC) results in rapid and complete engraftment in a large proportion of patients and in relatively fast immune recovery. Methods : We have analyzed by flow cytometry the immune reconstitution in 19 patients (pts) affected by multiple myeloma undergone to allogeneic HPC transplant from HLA-identical related donors after nonmyeloablative conditioning regimen with fludarabine 90 mg/m2 and cyclophosphamide 900 mg/m2. In each patient a comparable number of mononuclear cells, CD3+ T lymphocytes and CD34+ progenitor cells was infused. To evaluate the kinetics of the immune reconstitution, the overall number of total lymphocytes, T, B and NK cells of each patient were assessed before and 1, 2, 3, 6, 12, 18, 24, 30, 36 months after allogeneic HPC transplant. Results: Overall T cell reconstitution was in all the pts at 3 months, since at that time the CD3+ T cell median number was 880 cells/microl (r. 589–1,357). However, in all pts high numbers of CD3+ T cells were achieved at 12 months after transplant (median 1,326 cells/microl, r. 850–2,309). The CD4+ T cell median number was 281 cells/microl (r. 185–433) at 6 months, 391 cells/microl (r. 303–505) at 12 months, 603 cells/microl (r. 433–736) at 18 months. The CD8+ T cell median number was increased from the transplant to 18 months in which it was 1,489 cells/microl (r. 760–1,976). The decrease of CD8+ T cells with the normalization of CD4+/CD8+ ratio was observed at 30 months when CD4+ T cells were 650 cells/microl (r. 370–989) and CD8+ T cells were 690 cells/microl (r. 445–1,743). B cells recovery was observed at 18 months with a median number of 194 cells/microl (r. 40–404). The faster reconstitution was documented for NK cells with a median number of 314 cells/microl (r. 61–647) at 2 months. Conclusions: the complete immune reconstitution in our pts was achieved at 30 months after transplant. Our objective is to evaluate if this slow immune recovery is associated with a high incidence of infectious diseases and a low incidence of chronic GVHD. No significant financial relationships to disclose.
Plerixafor (AMD3100) in myeloma and lymphoma patients undergoing autologous stem cell transplantation
Authors: Moreb J. S. , Salmasinia D. , Cline C. , Rosenau E. 
Published: August 2020

7100 Background: Poor peripheral blood stem cell (PBSC) mobilization has been reported as an obstacle to autologous stem cell transplant (ASCT). Plerixafor (AMD3100) has been recently approved as a mobilization agent for PBSC in the setting of ASCT. Methods: We retrospectively analyzed the data on patients who received plerixafor in our institution over two-year period. Four lymphoma patients received the drug in their first cycle of mobilization and 17 patients (hard to mobilize, HTM) as a rescue after failing to achieve cell target using G-CSF alone. These patients include 8 multiple myeloma (MM) and 9 lymphoma patients. A control group of 26 randomly picked MM and lymphoma patients who were good mobilizers and received ASCT during the same period were used for comparison. Results: Sixteen of the 17 HTM patients proceeded to ASCT with median CD34+ cell dose of 3.68 X 106/kg (range, 1.88–5.01 X 106), and two of them had tandem transplants. All MM patients achieved minimum cell dose for two ASCTs. One MM patient died of progressive disease prior to ASCT. In comparison to the control group, plerixafor patients tended to have lower median CD34+ cell dose/kg collected and higher number of apheresis days, however the content of CFU-GM/kg on 1st day of apheresis was either equal or higher in the plerixafor group versus the control. The length of hospital stay, number of serious bacterial infection, time to granulocyte engraftment (AGC > 500) and long-term hematopoietic recovery at ≥ 12 mo post ASCT were not different among the two groups. Time to platelet recovery > 20,000/mm3 was similar for the MM patients, while more delayed for the plerixafor mobilized lymphoma patients (24 versus 12 days in the control group). One lymphoma patient in the control died of transplant-related complications before engraftment and none in the plerixafor group. Disease relapse at 12 months post ASCT was 0 and 10 % for plerixafor and control MM patients, respectively, and 46 and 20 % for lymphoma patients. However, the overall survival for both groups was not significantly different. Conclusions: all poor mobilizers were able to obtain adequate transplant CD34+ cell dose by using plerixafor and G-CSF. In general, patients mobilized with plerixafor had similar post transplant course and long-term outcome. [Table: see text]
Analyzing white blood cell subpopulation for quick and simple predictors for autologous stem cell collection
Authors: Gao Y. , Lim S. , Gao F. , Ng J. , Phoon Y. , Tham C. , Quek R. , Tao M. 
Published: August 2020

7101 Background: For patients undergoing peripheral stem cell harvesting, the current standard predictor for successful harvest is the peripheral blood (PB)CD34 count, which may have a slow turn-around time. Daily monitoring of CD34 count may not be cost-effective. This study aims to identify simple hematological parameters that can be used to predict for a single day CD 34+ stem cell yield of at least 1 x 10(6)/kg. Methods: 57 patients with lymphoproliferative malignancies who underwent autologous stem cell (ASC) harvesting were studied following DHAP, ICE or ESHAP chemotherapy. Eight main parameters were investigated to predict for a single day CD34 stem cell yield above 1x10(6)/kg: PB CD34+ cells, absolute monocyte count (AMC), AMC ratio, total white count (WBC), absolute lymphocyte count (ALC), ALC ratio, immature granulocyte count (IMC), IMC ratio and non-neutrophil cells (NNC). NNC was calculated by subtracting absolute neutrophil count from the total white count. The ratios were calculated by dividing the respective values on the first day of harvest with the values on the day before mobilizing chemotherapy started. Results: Linear regression showed a strong correlation between stem cell yield and CD34+ cells (R2=0.79, p<0.001), IMC ratio (R2=0.51, p<0.001) and AMC ratio (R2= 0.46, P<0.001). WBC and AMC showed a wide dispersion of results and were not reliable predictors of CD34 yield. On multivariate analysis, an IMC > 1 (p=0.03) and AMC ratio > 1 (p=0.002), ALC ratio > 1 (p=0.03) were independently predictive of a single day CD34 stem cell yield exceeding 1x10(6)/kgConclusions: Incorporating simple, routine hematolgic indices such as ALC and AMC ratio into a simple formula can be used to predict for ASC collection in addition to CD34+ count. This may be particularly useful when the turn-around-time to attain enumeration of CD34+ cells is slow or delayed on the same day of collection. No significant financial relationships to disclose.
A phase III trial of carboplatin, paclitaxel, and thoracic radiation therapy with or without thalidomide in patients with stage III non-small cell carcinoma of the lung (NSCLC): E3598
Authors: Schiller J. H. , Dahlberg S. E. , Mehta M. , Johnson D. H. 
Published: August 2020

7503 Background: Thalidomide (T) is an oral angiogenesis inhibitor with anti-tumor activity in hematological malignancies. Given that antiangiogenic drugs such as bevacizumab have proven activity in advanced NSCLC, ECOG conducted a phase III study to compare the effects of the addition of thalidomide to paclitaxel/carboplatin/radiation therapy (PC/RT) on overall survival (OS) in pts with newly diagnosed stage III NSCLC. Secondary endpoints included time to progression (PFS) and toxicity. Methods: Pts were required to have inoperable stage IIIA or IIIB (no pleural effusion) NSCLC and a PS of 0 or 1. Pts were randomized to receive 2 cycles of P (225 mg/m2)+ C (AUC=6) every 3 wks or PC + thalidomide starting at 200 mg daily with the possibility of dose escalation. This was followed by weekly C (AUC=2), P (45 mg/m2) and concurrent RT (60 Gy) ± T. Pts on PC/RT + T continued thalidomide for 24 mo. or until disease progression. Results: 277 eligible pts were randomized to PC/RT and 272 pts to PC/RT + T. Median age was 63; 61% of pts had stage IIIB disease, 35% had squamous histology, and 46% were PS 0. The third planned interim analysis was conducted with 403 of 506 planned deaths (73.9%) for full analysis and the trial was stopped early by the ECOG Data Monitoring Committee for futility. The median overall survival for the no T arm was 15.3 mo. (12.4–20.2 mo.) compared to 16.0 mo for the T arm (14.4–18.3 mo.); hazard ratio = 0.985 (0.81–1.19); p = 0.88. Median PFS for the no T arm was 7.6 mo. (6.6–8.7 mo.) compared to 8.0 mo. for the T arm (7.1–9.1 mo.), p>0.05. The most common toxicity on both arms was myelosuppression. 11% of pts on the T arm had a grade 3–5 thrombosis/embolism, compared to <3% on the no T arm. Conclusions: The addition of thalidomide to PC/RT in pts with stage III NSCLC does not provide a clinically significant benefit. [Table: see text]
Verification of the newly proposed T category (7th edition of the TNM classification) from a clinicopathologic viewpoint in non-small cell lung cancer
Authors: Yano T. , Morodomi Y. , Ito K. , Miura N. , Takenaka T. , Kawano D. , Shoji F. , Maehara Y. 
Published: August 2020

7533 Background: The proposed revision of the TNM classification by the International Association for the Study of Lung Cancer (IASLC) has been determined and validated based on the overall survival data. In the present study, we verified the T classification, which was the major point of revision regarding the newly proposed TNM classification, from a viewpoint of the clinico-pathologic findings at the primary tumor site. Methods: The medical records of 621 patients with primary non-small cell lung cancer (NSCLC) who underwent a complete resection at our institution from 1990 through 2003 were reviewed for the clinico-pathologic variables. The patients ranged in age from 31 to 87 years old with a mean of 66.4. The male:female ratio was 382:239. The adenocarcinoma:non-adenocarcinoma ratio was 449:220. Results: According to greatest dimension of the primary tumors, the 5-year postoperative survival was 77.8% for T1a (2cm>; n=168), 63.3% for T1b (3cm>; n=169), 46.4% for T2a (5cm>; n=205), 38.8% for T2b (7cm>; n=48), and 21.4% for T3 (7cm<; n=31) (p<0.001). The incidence of lymphatic permeation within the primary tumor was 12.5% for T1a, 17.2% for T1b, 29.8% for T2a, 35.4% for T2b, and 32.3% for T3 (T1b vs. T2a p<0.05). The incidence of vascular invasion within the primary tumor was 17.8% for T1a, 24.9% for T1b, 35.3% for T2a, 54.2% for T2b, and 64.5% for T3 (T1b vs. T2a, T2a vs. T2b, p<0.05). On the other hand, the incidence of pleural invasion of the primary tumor was 18.1 % for T1a, 29.4% for T1b, 49.3% for T2a, 47.3% for T2b, and 87.5% for T3 (T1a vs. T1b, T1b vs. T2a, T2b vs.T3, p<0.05). Significant differences were observed among the newly revised T subsets in at least one incidence of lymphatic permeation, vascular invasion or pleural invasion. Conclusions: The newly revised T classification, which is based mainly on the tumor dimension, is therefore considered both effective and appropriate for the pathological findings of the primary tumor. No significant financial relationships to disclose.