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  • 1
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5509-5509
    Abstract: Multiple prognostic models for patients with advanced Hodgkin’s disease have been developed in an effort to identify high-risk individuals for ASCT and predict outcomes of high dose therapy and transplant. The utility of four of these models was examined in a cohort of patients transplanted in our program between 1993 and 2005. A total of 113 patients with relapsed or refractory Hodgkin’s disease received ASCT. Forty-five patients received a conditioning regimen of busulfan, melphalan, and thiotepa (BuMelTT) whereas 68 patients received other standard conditioning regimens (SCR) including Cy/TBI/VP (23), CBV (39), and other (6). Median age is 34.5 years for BuMelTT and 34.0 years for SCR patients. Ninety-eight percent of patients receiving BuMelTT had at least two or more prior regimens compared with 86% SCR patients. Eighty-seven percent of BuMelTT and 93% of SCR patients had chemosensitive disease prior to transplant. Median followup is 113 weeks for BuMelTT patients versus 201 weeks for SCR patients. To date 37% of the BuMelTT and 56% of SCR patients have relapsed (p 〈 0.05) with a median time to relapse of 30 and 36 weeks (p=NS) respectively. Statistically significant factors differentiating the BuMelTT and SCR groups included median followup post-ASCT, total percent relapse after transplant, death after transplant, relapse in prior radiation field, and stage at salvage therapy pre-ASCT. Median OS, EFS, and RFS have not yet been reached for BuMelTT patients compared with 439 (p=0.03), 67 (p=NS), and 74 (p=NS) weeks for the SCR patients. TRM was five percent in both groups at five years. We investigated the predictive value of four prognostic models on the entire group, BuMelTT and SCR cohorts. Models evaluated included Roswell Park (RPCI), Memorial Sloan-Kettering, German Hodgkin’s Study Group, and Southwestern Oncology Group (SWOG). Each of these models has identified three negative prognostic indicators on the basis of multivariate analysis. Patients who had 0 or 1 factor were considered good risk and those that had 2 or 3 factors poor risk. Only the SWOG model ( 〉 2 prior regimens, relapse in previous radiation field, extranodal disease) was predictive for OS for the entire group (p 〈 0.01) and for the BuMelTT (p=0.05) and SCR (p 〈 0.01) cohorts. The SWOG model was also able to differentiate EFS between good and poor risk patients for the entire group (p=0.02) and SCR group (p=0.05) but not for the BuMelTT cohort. None of the models could differentiate between good and poor risk patients with regard to RFS. When good and poor risk were defined as 0 factors versus 1 to 3 factors, the RPCI model (chemotherapy-resistant disease, poor performance status, and 3 or more chemotherapy regimens prior to transplant) was predictive of OS (p=0.02) and EFS (p=0.02) but only for the BuMelTT cohort. These results suggest that BuMelTT may improve long-term outcomes in patients with advanced Hodgkin’s disease. The prognostic models evaluated had limited utility in our patient cohort with only the SWOG model being predictive of outcome. Large multi-institutional studies are needed to improve prognostic models for transplantation in advanced Hodgkin’s disease.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3021-3021
    Abstract: No randomized trials have compared autologous HCT (autoHCT) to allogeneic HCT (alloHCT) for DLBCL. We analyzed the outcomes of 916 patients (pts) (837 autoHCT and 79 alloHCT) ages 18–60yrs after a first autoHCT or HLA-identical sibling alloHCT for DLBCL between 1995 and 2003 reported to the CIBMTR. Pts receiving T-cell depleted allografts or reduced-intensity conditioning were excluded. There were significant baseline differences between the groups in disease stage, B symptoms, extranodal disease and marrow involvement. AlloHCT pts were significantly more likely to have 〉 3 chemo regimens prior to HCT (53 vs 40%), and resistant induction failure or relapse (39 vs 16%). At 1yr, treatment-related mortality (TRM) was higher after alloHCT (41%, 95% CI, 30–52%) than after autoHCT (11%, 95% CI, 9–14%, p 〈 0.001), but risks of relapse/progression were similar (30%, 95% CI, 21–41%) and (33%, 95% CI, 29–36%, p=0.69), respectively. Cumulative incidence of outcomes and univariate probabilities of progression free (PFS) and overall survival (OS) at 5 yrs are summarized in table 1. In multivariate analysis, allo and autoHCT had differential early and late effects on outcomes. In the first 12 mo after transplant, alloHCT was associated with higher TRM (RR 4.76, 95% CI, 3.14–7.22, p 〈 0.001), treatment failure (RR 2.08, 95% CI, 1.56–2.77, p 〈 0.001) and mortality (RR 2.78, 95% CI, 2.06–3.77, p 〈 0.001) but similar risk of progression (RR 1.14, 95% CI, 0.75–1.74, p=0.54) compared to autoHCT. Among pts surviving 12 mo post-transplant, no significant difference was observed between autoHCT and alloHCT for TRM, progression, PFS, or OS. Covariates that increased the risks of TRM and OS were older age (51–60 years), KPS 〈 90%, chemoresistance at transplant, and earlier transplant yr (before 2001 vs later). Older age and chemoresistance were also associated with progression and lower PFS. There were no significant interactions between graft type and other prognostic variables; in particular, relative risk of outcomes with allo vs autoHCT were similar for patients with chemosensitive and chemoresistant disease. In summary, myeloablative alloHCT increased risks of early TRM and mortaliy without an effect on progression (compared to autoHCT). Transplant type did not affect outcomes after 12 months post-transplant. AutoHCT was associated with superior survival (fig 1), and the difference was not explained by differences in chemosensitivity at the time of transplant. AutoHCT AlloHCT Outcomes (95%CI) (95%CI) AGVHD @ day 100 N/A 42 (31–53) CGVHD @ 5yrs N/A 27 (18–38) TRM @ 5yrs 18 (15–20) 45 (34–57) Relapse/progression @ 5yrs 39 (36–43) 33 (23–44) PFS @ 5yrs 43 (40–46) 26 (18–37) OS @ 5yrs 49 (46–53) 27 (18–27) Figure 1 Figure 1.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 3
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5237-5237
    Abstract: Background: Patients with diffuse large B-cell lymphoma (DLBCL) who present with extra-nodal involvement or histologic transformation from low-grade disease have lower rates of survival after conventional-dose therapy. The impact of these features on outcomes after high-dose therapy with autologous transplantation was investigated. Methods: We retrospectively reviewed the outcomes of 64 consecutive patients receiving autologous transplantation from 1995 to 2003 for the treatment of DLBCL. Variables considered were age, gender, histologic transformation, history of bone marrow involvement, history of central nervous system (CNS) involvement, time from diagnosis to transplant, number of pre-transplant regimens, chemosensitivity prior to transplant, conditioning regimen, year of transplant, and the use of peripheral blood or bone marrow stem cells. Survivals were estimated by the Kaplan-Meier method. The Cox proportional hazards regression model was used to test the significance of factors on survival. Univariate association between variables and survival were tested by the log-rank test. Correlation between variables was tested with Spearman’s rank coefficient. Results: The median age at transplant among 64 patients was 53.5 years (17–74). The median overall survival was 3.3 years. Among these patients, 12 had a history of CNS involvement, 10 had a history of bone marrow involvement, and 12 had transformed from low-grade lymphoma. A Cox regression model suggested age 〈 50 (log-rank, p=0.093), 〈 2 regimens prior to transplant (log-rank, p=0.052), and the lack of BEAM as conditioning regimen (log-rank, p=0.019) as multivariate factors for survival. However, the use of BEAM was highly associated with older age (R²= 0.42, p=0.001) and more prior chemotherapy regimens (R²=0.24, p=0.054). A history of extranodal involvement, including prior CNS involvement (p=0.842) or bone marrow involvement (p=0.518), was not associated with lower survival by univariate analysis. No significant association was found between survival and a history of transformation (p=0.484). Conclusions: A history of CNS involvement, bone marrow involvement, or histologic transformation is not associated with lower rates of survival among patients undergoing autologous transplantation for diffuse large B-cell lymphoma at our institution. Patients who present with such histories remain candidates for autologous transplantation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 4
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5460-5460
    Abstract: The inability to mobilize sufficient number of hematopoietic stem cells (HSC) using standard cytokine-assisted mobilization strategies excludes eligible patients from potentially curative autologous stem cell transplantation (ASCT). AMD3100, a novel antagonist of the SDF-1α / CXCR4 complex, has been reported to augment peripheral stem cell (PBSC) mobilization in patients undergoing their first planned stem cell collection attempt. AMD3100 can rapidly increase circulating CD34+ progenitor cells in preclinical murine models and healthy volunteers, alone or in combination with G-CSF. In phase II trials, when combined with G-CSF, AMD3100 appeared effective at mobilizing heavily pretreated patients during their first apheresis (Stiff, ASBMT, 2005). The ability of AMD3100 plus G-CSF to mobilize patients who were unable to collect significant CD34+ cells with G-CSF also has been observed. Patients undergoing their first attempt at PBSC mobilization were enrolled in a cross-over design trial comparing G-CSF with G-CSF and AMD3100 (Flomenberg, BLOOD, 2005). Nine patients did not mobilize PBSC when initially treated with G-CSF, but were subsequently collected when treated with AMD3100 plus G-CSF. In contrast, no patients on the AMD3100 + G-CSF arm failed to mobilize adequate PBSC. AMD3100 has been available on compassionate use for patients, otherwise eligible for ASCT but who have failed to mobilize adequate PBSC. Effective rescue of patients was been achieved in 〉 50% of the population (McGuirk, ASH, 2005). Our center has participated in this compassionate use program and seven patients (4 NHL, 1 Hodgkin’s Disease, 1 AILD, 1 myeloma) were enrolled in a local IRB- approved compassionate use protocol using AMD3100 in combination with G-CSF. A detailed analysis of these seven patients has been performed. Pretreatment characteristics include: patient median age was 58, median # of previous chemotherapy regimens was 3, and that five patients had failed chemotherapy + growth factor based PBSC mobilization strategies. Two patients had undergone previous autologous transplantation and that of the 5 patients for whom PBSC collection was attempted, the median # of CD34 progenitors collected was 0.53 × 106/kg. Results: 6 of seven patients had successful mobilization of CD34+ PBSC when treated with the combination treatment strategy with the median number of CD34+ progenitors/kg = 3.6 × 106 with a mean of 2.3 days for collection (median = 2 days). All six of the patients have since gone on to ASCT and all have had documented engraftment with median time to ANC of 500 by Day 12 and median time to platelet counts of 20,000 and 50,000 by Days 24 and 37, respectively. Only the myeloma patient who had previously undergone two independent ASCT, among other treatments, failed to mobilize PBSC and was unable to pursue ASCT. Thus, we confirm the ability to rescue G-CSF failures (1 patient) as well as demonstrate that patients who fail G-CSF plus chemotherapy mobilization attempts (5 of 6 patients) can effectively be rescued with a combination of AMD3100 and G-CSF. We have found this strategy safe and we recommend this combination mobilization strategy for patients with failed PBSC mobilization attempts to allow patients to pursue ASCT options.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5315-5315
    Abstract: Background: Vancomycin-resistant enterococci (VRE) have become increasingly important nosocomial pathogens in very ill and immunocompromised hospitalized patients (pts). Due to an increase in VRE clinical cultures including bacteremias on our institutional transplant/leukemia service in early 2004, active surveillance for VRE among this population was instituted in June 2004. We describe here the incidence and prevalence of VRE colonization and infection in this population over a two year study period, as well as selected pt demographics and mortality associated with VRE bacteremia. Methods: Between June 2004 and July 2006, active surveillance for VRE on inpatients on the transplant/leukemia service was performed by acquiring perirectal or stool swabs for VRE culture on hospital admission and on a weekly basis while inpatient. Acquisition of VRE was determined to be nosocomial if the initial culture was negative followed by a positive culture at any time during the hospital stay. Multiple sequential interventions as recommended by the Society for Healthcare and Epidemiology (SHEA) guidelines were implemented. Pt census data and daily isolation indicators were used to help determine VRE colonization rates and the prevalence of VRE on the units. Chart reviews were performed to obtain information on clinical pts related features and mortality of bacteremic pts. Results: Nineteen percent (193/1019) of pts screened were colonized with VRE with the monthly nosocomial colonization rate ranging from 2–12% (rate/1000 patient days). Eighteen percent (31/189) of pts newly colonized with VRE became bacteremic, including 7/31 who had bacteremia as their primary presentation. Of the bacteremic pts, 24 (77.4%) died at a median of 20 days (range 2–208 days), 18 (75%) dying during their bacteremic hospitalization of multiple causes. Sixteen had acute leukemia, 11 non-Hodgkin’s lymphoma, and 3 other malignancies. Eighteen bacteremic pts had undergone allogeneic transplant & 5 autologous transplant. Fourteen of 18 allogeneic transplant pts had active GVHD and all 18 were on immune suppression therapy. Of all allogeneic transplants performed during the study period, 13% (18/140) were complicated by VRE bacteremia. Sixteen bacteremic pts required ICU stays, while 6 had C. difficile colitis and 5 mucositis during the same hospital stay. SHEA recommended interventions instituted at various times (e.g. enhanced contact and barrier precautions for colonized pts, “supercleans” of unit, written communication to staff, pts and families, gloving for all pt contacts) did not have a durable effect on these rates. However, the ratio of new nosocomial cases/overall prevalence of VRE in the units decreased 20% over the study period, suggesting some measure of control despite high colonization pressure. Assessment of response to intensive control strategies as well as delineation of risk factors for bacteremia and death in this population are ongoing and will be presented. Conclusion: Despite application of standardized guidelines for VRE control, affecting a marked and durable decrease in endemic VRE colonization on a complicated transplant/leukemia service is difficult. VRE bacteremia following colonization in transplant/leukemia pts is common and is associated with early mortality. VRE control remains critical, and new modalities and approaches are essential.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 6
    Online Resource
    Online Resource
    American Society for Microbiology ; 2009
    In:  Antimicrobial Agents and Chemotherapy Vol. 53, No. 2 ( 2009-02), p. 428-434
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 53, No. 2 ( 2009-02), p. 428-434
    Abstract: Daptomycin is the first antibacterial agent of the cyclic lipopeptides with in vitro bactericidal activity against gram-positive organisms, including vancomycin-resistant enterococci, methicillin-resistant staphylococci, and glycopeptide-resistant Staphylococcus aureus . The pharmacokinetics of daptomycin were determined in 29 adult oncology patients with neutropenic fever. Serial blood samples were drawn at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after the initial intravenous infusion of 6 mg/kg of body weight daptomycin. Daptomycin total and free plasma concentrations were determined by high-pressure liquid chromatography. Concentration-time data were analyzed by noncompartmental methods. The results (presented as means ± standard deviations and ranges, unless indicated otherwise) were as follows: the maximum concentration of drug in plasma ( C max ) was 49.04 ± 12.42 μg/ml (range, 21.54 to 75.20 μg/ml), the 24-h plasma concentration was 6.48 ± 5.31 μg/ml (range, 1.48 to 29.26 μg/ml), the area under the concentration-time curve (AUC) from time zero to infinity was 521.37 ± 523.53 μg·h/ml (range, 164.64 to 3155.11 μg·h/ml), the volume of distribution at steady state was 0.18 ± 0.05 liters/kg (range, 0.13 to 0.36 liters/kg), the clearance was 15.04 ± 6.09 ml/h/kg (range, 1.90 to 34.76 ml/h/kg), the half-life was 11.34 ± 14.15 h (range, 5.17 to 83.92 h), the mean residence time was 15.67 ± 20.66 h (range, 7.00 to 121.73 h), and the median time to C max was 0.6 h (range, 0.5 to 2.5 h). The fraction unbound in the plasma was 0.06 ± 0.02. All patients achieved C max /MIC and AUC from time zero to 24 h (AUC 0-24 )/MIC ratios for a bacteriostatic effect against Streptococcus pneumoniae . Twenty-seven patients (93%) achieved a C max /MIC ratio for a bacteriostatic effect against S. aureus , and 28 patients (97%) achieved an AUC 0-24 /MIC ratio for a bacteriostatic effect against S. aureus . Free plasma daptomycin concentrations were above the MIC for 50 to 100% of the dosing interval in 100% of patients for S. pneumoniae and 90% of patients for S. aureus . The median time to defervescence was 3 days from the start of daptomycin therapy. In summary, a 6-mg/kg intravenous infusion of daptomycin every 24 h was effective and well tolerated in neutropenic cancer patients.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2009
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 7
    In: Ultrasound in Medicine & Biology, Elsevier BV, Vol. 49, No. 1 ( 2023-01), p. 72-89
    Type of Medium: Online Resource
    ISSN: 0301-5629
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1498918-9
    SSG: 12
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  • 8
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 12856-12858
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e19503-e19503
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e19503-e19503
    Abstract: e19503 Background: Approximately 1.6 million new cancer cases are expected to be diagnosed in 2012 in the United States, making the need for generic cancer treatment drugs widespread. Methods: In late 2011, LIVESTRONG fielded the Drug Shortage Survey, which mirrored the questions from the American Hospital Association drug shortage survey for providers reworded for a patient audience. The primary goals of the brief survey were to 1) assess if survivors were aware of a generic drug shortage in the U.S. and 2) gauge the impact that the drug shortage has had on people affected by cancer. Individuals were asked to participate in this online survey through a number of means (including the LIVESTRONG Blog). Results: Between October 31, 2011 and January 30, 2012, 114 individuals completed the drug shortage survey, including 54 individuals who have been personally diagnosed with cancer. A little under half of the respondents (47%) felt they or a loved one had been impacted by the drug shortage, while an additional 30% were not sure if they had been impacted. Of the individuals impacted, the most commonly reported adverse effects of the drug shortage were not receiving medications needed for cancer treatment (40%) and receiving different medications (36%). The table highlights the reported effects. Conclusions: Results from this survey indicate that for cancer survivors who chose to participate in this survey who had been impacted by the drug shortage, the impact has been very significant. Additionally, results indicate that more information may need to be disseminated to the patient population about the drug shortage. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 9136-9136
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 9136-9136
    Abstract: 9136 Background: Treatment summaries (TS), a critical component of survivorship care plans, were identified as a tool to improve long-term outcomes for the 12 million cancer survivors alive in the US. Methods: In 2010, the Lance Armstrong Foundation fielded the LIVESTRONG Survey for People Affected by Cancer. Respondents were recruited through several channels including partnerships with national organizations such as ASCO. Over a 9 month period, more than people completed the survey, including 3,682 post-treatment cancer survivors (PTCS). The survey addressed post-treatment concerns including receipt of TS. Full survey results were presented at the 2011 ASCO Conference. Results: Receipt of TS data was available for 3042 PTCS: average age (50); female (65%); average time since diagnosis (6 years); received a TS (34%). PTCS who received TS reported that they were: Closer to time since diagnosis or since treatment ended (p 〈 0.01); more likely to have received chemotherapy (p 〈 0.01); more often receiving the majority of their health care from a medical oncologist (p 〈 0.05); experiencing significantly fewer (p 〈 0.05) post-treatment emotional concerns (including emotional distress; fears of recurrence; concerns about family risk; and appearance concerns) and were more likely to have received care; significantly less likely to say that they had “learned to live with” their concerns (p 〈 0.05) – the most common reason among participants for not receiving care. Finally, receipt of a TS was related to higher information efficacy (p 〈 0.01; which appeared to mediate the relationship between receipt of a TS and fewer emotional concerns). PTCS who received a TS more often reported that their needs were met including information received about possible late-effects; care they got during treatment; and care they received after treatment. Conclusions: These results support the provision of TS to PTCS. Receipt of TS was associated with a variety of positive outcomes; however, only about one-third of PTCS received one. Future studies focused on patient perspectives on care planning tools, such as treatment summaries and care plans, can help to improve optimal survivorship care delivery.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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