Julie M Vose

The Nebraska Medical Center, Omaha, Nebraska, United States

Are you Julie M Vose?

Claim your profile

Publications (384)3093.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Central nervous system complications (CNSCs) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (ALLO-HSCT). We aimed to determine the incidence of CNSCs and its impact on survival. Methods This retrospective cohort study included patients with hematological disorders, who received ALLO-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. Results Of the 351 patients identified, forty-five patients developed CNSCs (12.8%). The 100-day cumulative incidence of CNSCs was 8% (95% confidence interval [CI] 8-15%). The most common CNSCs included: posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSCs (14% vs. 44%, p=0.0004). In multivariate analysis, the risk of mortality for patients with versus without CNSCs was significantly higher (hazard ratio 1.56, 95% CI 1.03–2.36, p= 0.04). Conclusions The occurrence of CNSCs after ALLO-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection and management of CNSCs post ALLO-HSCT is needed to improve outcomes.
    Clinical Lymphoma, Myeloma and Leukemia 06/2015; DOI:10.1016/j.clml.2015.06.004 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease. We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients treated across 19 North American centers. Forty-three percent of patients presented with mediastinal disease (MGZL), while 57% did not (NMGZL). NMGZL patients were older ((50 versus 37 years,) (P) (=0.0001); more often had) bone marrow involvement (19% versus 0%, P=0.001); >1 extranodal site (27% versus 8%, P=0.014); and advanced stage disease (81% versus 13%, respectively, P=0.0001); but less bulk (8% versus 44%, respectively, P=0.0001). Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, MGZL outcomes appeared similar compared with NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P=0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (HR 1.88, 95%CI 1.03-3.83, P=0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (HR 0.35, 95%CI 0.18-0.69, P=0.002). Collectively, GZL is a heterogeneous and likely more common entity that includes non-mediastinal presentation, while outcomes appear superior when treated with a rituximab-based, DLBCL-specific regimen. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    American Journal of Hematology 06/2015; DOI:10.1002/ajh.24082 · 3.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mediastinal involvement is considered essential for the diagnosis of primary mediastinal large B-cell lymphoma (PMBL). However, we have observed cases of diffuse large B-cell lymphoma (DLBCL) with features of PMBL but without detectable mediastinal involvement. The goal was to assess our previously established gene expression profiling (GEP) signature for PMBL in classifying these cases. In a large series of DLBCL cases, we identified 24 cases with a GEP signature of PMBL, including 9 cases with a submission diagnosis of DLBCL consistent with PMBL (G-PMBL-P) and 15 cases with a submission diagnosis of DLBCL. The pathology reviewers agreed with the diagnosis in the 9 G-PMBL-P cases. Among the other 15 DLBCL cases, 11 were considered to be PMBL or DLBCL consistent with PMBL, 3 were considered to be DLBCL, and 1 case was a gray-zone lymphoma with features intermediate between DLBCL and classical Hodgkin lymphoma. All 9 G-PMBL-P and 9 of the 15 DLBCL cases (G-PMBL-M) had demonstrated mediastinal involvement at presentation. Interestingly, 6 of the 15 DLBCL cases (G-PMBL-NM) had no clinical or radiologic evidence of mediastinal involvement. The 3 subgroups of PMBL had otherwise similar clinical characteristics, and there were no significant differences in overall survival. Genetic alterations of CIITA and PDL1/2 were detected in 26% and 40% of cases, respectively, including 1 G-PMBL-NM case with gain of PDL1/2. In conclusion, PMBL can present as a nonmediastinal tumor without evidence of mediastinal involvement, and GEP offers a more precise diagnosis of PMBL.
    The American journal of surgical pathology 05/2015; DOI:10.1097/PAS.0000000000000473 · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated the significance of MYC, BCL2 and BCL6 gene abnormalities in a cohort of 205 diffuse large B-cell lymphoma (DLBCL) patients studied by conventional and/or fluorescence in situ hybridization cytogenetic analysis. Combining these methods, 172 cases (84%) were classified as MYC-, 17 (8%) were MYC+/BCL2-/BCL6-, and 16 (8%) were double/triple-hit lymphomas (i.e. MYC+/BCL2+, MYC+/BCL6+, or MYC+/BCL2+/BCL6+). We found a significant difference in EFS among the three groups (p=0.02), with the double/triple-hit group having the worst EFS. Patients who were MYC+, but BCL2- and BCL6-, had the best EFS. We conclude that patients with MYC+ DLBCL, but without BCL2 or BCL6 abnormalities, do not have a worse outcome when compared to those who are MYC-. However, patients with double/triple-hit DLBCL have a very poor outcome and should be treated with aggressive or novel therapies.
    Leukemia & lymphoma 04/2015; DOI:10.3109/10428194.2015.1034699 · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of hematopoietic cell transplantation (HCT) in the therapy of Hodgkin lymphoma (HL) in pediatric and adult patients is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are included and were reached unanimously by a panel of HL experts. Both autologous and allogeneic HCT offer a survival benefit in selected patients with advanced or relapsed HL and are currently part of standard clinical care. Relapse remains a significant cause of failure after both transplant approaches and strategies to decrease the risk of relapse remain an important area of investigation. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2015; 21(6). DOI:10.1016/j.bbmt.2015.02.022 · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the mortality patterns of patients with lymphoma and myeloma, who have undergone autologous hematopoietic stem cell transplantation (ASCT) might identify improvement opportunities. The present retrospective study included patients with lymphoma and myeloma, aged ≥ 18 years, who had undergone ASCT from 1983 to 2010 at the University of Nebraska Medical Center. Of the 2284 patients, 972 had died within first 5 years after ASCT. The patients were divided into 3 cohorts according to the time of transplantation: 1983 to 1990 (cohort I), 1991 to 2000 (cohort II), and 2001 to 2010 (cohort III). Using Cox proportional hazards regression analysis, the risk of cause-specific mortality was compared across the 3 cohorts. Of a total of 1215 deaths, 972 (80%) occurred within the first 5 years after ASCT. Disease relapse (73.4%), organ failure (7.8%), infection (4.7%), and secondary malignancy (4.2%) accounted for most of the deaths. The risk of death from infection (P < .0001), but not from relapse (P = .26), organ failure (P = .68), or secondary malignancy (P = .15), had declined in the more recent cohorts. The 5-year overall survival of patients undergoing ASCT has improved significantly owing to a decline in infectious mortality. Our results highlight that the mortality from relapse remains the most common cause of death, warranting investigation of different strategies to reduce the incidence of relapse and improve the therapy for relapse after ASCT. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical lymphoma, myeloma & leukemia 03/2015; DOI:10.1016/j.clml.2015.02.024 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, which are managed in the same way. The advent of novel monoclonal antibodies (ofatumumab and obinutuzumab) led to the development of effective chemoimmunotherapy regimens. The recently approved small molecule kinase inhibitors (ibrutinib and idelalisib) are effective treatment options for CLL in elderly patients with decreased tolerance for aggressive regimens and in patients with poor prognostic features who do not benefit from conventional chemoimmunotherapy regimens. This portion of the NCCN Guidelines for Non-Hodgkin's Lymphomas describes the recent specific to the incorporation of recently approved targeted therapies for the management of patients with newly diagnosed and relapsed or refractory CLL/SLL. Copyright © 2015 by the National Comprehensive Cancer Network.
    Journal of the National Comprehensive Cancer Network: JNCCN 03/2015; 13(3):326-62. · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extranodal natural killer/T-cell lymphoma, nasal type (NKTL) is an uncommon aggressive subtype of non-Hodgkin lymphoma, which is significantly more common in East Asia and Latin America. Three-quarters of patients present with stage I/II disease, and half of patients have a low-risk International Prognostic Index score. Although additional factors including natural killer/T-cell lymphoma prognostic index and peripheral blood Epstein-Barr virus load influence the outcomes, the modality of treatment largely differs according to stage (based on nonrandomized studies). In early-stage disease, a combination of chemotherapy and involved-field radiotherapy (IFRT) appears to improve outcome compared with chemotherapy alone. Radiotherapy dose > 50 Gy, concurrent or sequential chemoradiation, and early use of IFRT results in better outcomes than doses < 50 Gy and delay in initiation of IFRT. In late-stage NKTL, chemotherapy alone is the mainstay of treatment. Compared with the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, newer regimens containing L-asparaginase and gemcitabine result in better outcomes; however, toxicity might be an issue. Stem cell transplant has been used as salvage and consolidation therapy with some benefit, particularly in patients with advanced-stage disease in remission at the time of transplant; however, further confirmatory studies are needed. In the past decade, we have seen a significant growth in our understanding of the disease process and an increase in our armamentarium of effective therapeutics; however, further development of novel therapies and optimal selection of available therapy options via randomized trials are necessary to improve the outcomes of this aggressive lymphoma. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Lymphoma, Myeloma and Leukemia 01/2015; 15(5). DOI:10.1016/j.clml.2014.12.014 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied the global miRNA expression in diffuse large B-cell lymphoma (DLBCL; n=79), Burkitt lymphoma (BL; n= 36), primary mediastinal B-cell lymphoma (PMBL; n=12), B-cell lines (n=11), and normal subsets of naïve B-cells (N), centroblasts (CB), and peripheral blood B-cells along with their corresponding gene expression profiles (GEP). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared to ABC-DLBCL (p=0.002). We identified a 27-miRNA signature that included MYC targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155 which significantly associated with R-CHOP response failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to AKT inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL. Copyright © 2014 American Society of Hematology.
    Blood 12/2014; DOI:10.1182/blood-2014-04-566778 · 10.43 Impact Factor
  • Vijaya Raj Bhatt, Julie M. Vose
    [Show abstract] [Hide abstract]
    ABSTRACT: Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. Copyright © 2014 Elsevier Inc. All rights reserved.
    Hematology/Oncology Clinics of North America 12/2014; DOI:10.1016/j.hoc.2014.08.015 · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study describes the supply of cancer care providers-physicians, nurse practitioners (NPs), and physician assistants (PAs)-in Nebraska and analyzes changes in the supply over a 5-year period.
    Journal of Oncology Practice 11/2014; 11(1). DOI:10.1200/JOP.2014.001565
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The maximum tolerated dose of SAR245409, a pan-Class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, was determined in a phase 1 dose-escalation study in advanced solid tumors. We report safety, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of SAR245409 capsules 50 mg twice daily in an expansion cohort of 16 patients with relapsed/refractory lymphoma. The most common treatment-related adverse events (AEs) were nausea (31.3%) and diarrhea (25.0%). The most common grade 3/4 treatment-related AE was increased alanine aminotransferase (12.5%). PK results were consistent with solid tumors, confirming a relatively short steady-state half-life (mean 4.61 hours). Among 12 evaluable patients, one complete response and two partial responses (PRs) were achieved in patients with and without PI3K/mTOR pathway alterations. In a patient with mantle cell lymphoma achieving PR, SAR245409 was associated with significant inhibition of PI3K/mTOR and ERK pathways. Preliminary efficacy warrants further evaluation of SAR245409 in lymphoma.
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND The treatment and outcomes of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma (HL) continue to evolve. The International Prognostic Score (IPS) is used to predict the survival of patients with advanced-stage HL, but it has not been validated in patients with HIV infection.METHODS This was a multi-institutional, retrospective study of 229 patients with HIV-associated, advanced-stage, classical HL who received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus combination antiretroviral therapy. Their clinical characteristics were presented descriptively, and multivariate analyses were performed to identify the factors that were predictive of response and prognostic of progression-free survival (PFS) and overall survival (OS).RESULTSThe overall and complete response rates to ABVD in patients with HIV-associated HL were 91% and 83%, respectively. After a median follow-up of 5 years, the 5-year PFS and OS rates were 69% and 78%, respectively. In multivariate analyses, there was a trend toward an IPS score >3 as an adverse factor for PFS (hazard ratio [HR], 1.49; P=.15) and OS (HR, 1.84; P=.06). A cluster of differentiation 4 (CD4)-positive (T-helper) cell count <200 cells/μL was associated independently with both PFS (HR, 2.60; P=.002) and OS (HR, 2.04; P=.04). The CD4-positive cell count was associated with an increased incidence of death from other causes (HR, 2.64; P=.04) but not with death from HL-related causes (HR, 1.55; P=.32).CONCLUSIONS The current results indicate excellent response and survival rates in patients with HIV-associated, advanced-stage, classical HL who receive ABVD and combination antiretroviral therapy as well as the prognostic value of the CD4-positive cell count at the time of lymphoma diagnosis for PFS and OS. Cancer 2014. © 2014 American Cancer Society.
    Cancer 09/2014; 121(3). DOI:10.1002/cncr.29066 · 4.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with double hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT), on outcomes of 311 patients with previously-untreated DHL. At median follow-up of 23 months, the median progression free survival (PFS) and overall survival (OS) among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at two years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (p=0.14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH> three times upper limit of normal, were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high, intermediate, and low risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.
    Blood 08/2014; 124(15). DOI:10.1182/blood-2014-05-578963 · 10.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22-44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free.Bone Marrow Transplantation advance online publication, 28 July 2014; doi:10.1038/bmt.2014.161.
    Bone Marrow Transplantation 07/2014; 49(11). DOI:10.1038/bmt.2014.161 · 3.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND The objective of this study was to compare the outcomes of patients with classical Hodgkin lymphoma (cHL) who achieved complete remission with frontline therapy and then underwent either clinical surveillance or routine surveillance imaging.METHODS In total, 241 patients who were newly diagnosed with cHL between January 2000 and December 2010 at 3 participating tertiary care centers and achieved complete remission after first-line therapy were retrospectively analyzed. Of these, there were 174 patients in the routine surveillance imaging group and 67 patients in the clinical surveillance group, based on the intended mode of surveillance. In the routine surveillance imaging group, the intended plan of surveillance included computed tomography and/or positron emission tomography scans; whereas, in the clinical surveillance group, the intended plan of surveillance was clinical examination and laboratory studies, and scans were obtained only to evaluate concerning signs or symptoms. Baseline patient characteristics, prognostic features, treatment records, and outcomes were collected. The primary objective was to compare overall survival for patients in both groups. For secondary objectives, we compared the success of second-line therapy and estimated the costs of imaging for each group.RESULTSAfter 5 years of follow-up, the overall survival rate was 97% (95% confidence interval, 92%-99%) in the routine surveillance imaging group and 96% (95% confidence interval, 87%-99%) in the clinical surveillance group (P = .41). There were few relapses in each group, and all patients who relapsed in both groups achieved complete remission with second-line therapy. The charges associated with routine surveillance imaging were significantly higher than those for the clinical surveillance strategy, with no apparent clinical benefit.CONCLUSIONS Clinical surveillance was not inferior to routine surveillance imaging in patients with cHL who achieved complete remission with frontline therapy. Routine surveillance imaging was associated with significantly increased estimated imaging charges. Cancer 2014. © 2014 American Cancer Society.
    Cancer 07/2014; 120(14). DOI:10.1002/cncr.28698 · 4.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The poor prognosis of diffuse large B-cell lymphoma (DLBCL) patients relapsing within 1-year of initial diagnosis after first-line rituximab-based chemoimmunotherapy has created controversy about the role of autologous transplantation (auto-HCT) in this setting. We compared auto-HCT outcomes of chemosensitive DLBCL patients between 2000 and 2011 in two cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1-year of initial diagnosis. The ERF cohort was compared with those relapsing >1-year after initial diagnosis (Late Rituximab Failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Non-relapse mortality (NRM), progression/relapse, progression-free survival (PFS) and overall survival (OS) of ERF vs. LRF cohorts at 3-years were 9% (95%CI 6-13) vs. 9% (95%CI 5-13), 47% (95%CI 41-52) vs. 39% (95%CI 33-46), 44% (95%CI 38-50) vs. 52% (95%CI 45-59) and 50% (95 CI 44-56) vs. 67% (95%CI 60-74), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk (RR) 1.31, p=0.34). ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR 2.08, p<0.001) and overall mortality (RR 3.75, p<0.001) within the first 9 months post auto-HCT. Beyond this period, PFS and OS were not significantly different between ERF and LRF cohorts. Auto-HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS 44%), and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2014; 20(11). DOI:10.1016/j.bbmt.2014.06.036 · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Published guidelines recommend baseline cardiac function testing before initiating anthracycline-based chemotherapy. These recommendations are based largely on consensus, and there is little information regarding how often testing leads to alterations in therapy or whether testing is able to predict subsequent cardiac toxicity.
    Clinical Lymphoma, Myeloma and Leukemia 06/2014; 15(1). DOI:10.1016/j.clml.2014.06.026 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PRO131921 is a third-generation, humanized anti-CD20 monoclonal antibody with increased antibody-dependent cytotoxicity and complement-dependent cytotoxicity compared to rituximab. In this phase I study, PRO131921 was administered as a single agent to patients with CD20+, relapsed or refractory, indolent non-Hodgkin's lymphoma (NHL) who had been treated with a prior rituximab-containing regimen. The primary aim of this study was safety and tolerability of PRO131921. The secondary aim of the study, and focus of this report, was to determine the pharmacokinetics (PK) profile of PRO131921 and establish a correlation between drug exposure and clinical efficacy. Patients were treated with PRO131921 by intravenous infusion weekly for 4 weeks and the dose was escalated based on safety in a 3+3 design. Twenty-four patients were treated with PRO131921 at doses from 25 mg/m(2) to 800 mg/m(2). Analysis of PK data demonstrated a correlation between higher normalized drug exposure (normalized AUC) and tumor shrinkage (p=.0035). Also, normalized AUC levels were higher among responders and subjects displaying tumor shrinkage versus subjects progressing or showing no regression (p=0.030). In conclusion, PRO131921 demonstrated clinical activity in rituximab-relapsed and refractory indolent NHL patients. The observation that higher normalized AUC may be associated with improved clinical responses has potential implications in future trials of monoclonal antibody-based therapies, and emphasizes the importance of early PK studies to optimize antibody efficacy.
    Clinical Immunology 06/2014; 154(1). DOI:10.1016/j.clim.2014.06.005 · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.
    Journal of Clinical Oncology 05/2014; 32(17). DOI:10.1200/JCO.2012.43.9273 · 17.88 Impact Factor

Publication Stats

20k Citations
3,093.58 Total Impact Points


  • 2000–2015
    • The Nebraska Medical Center
      Omaha, Nebraska, United States
  • 1989–2015
    • University of Nebraska Medical Center
      • • Division of Oncology and Hematology
      • • Department of Internal Medicine
      • • Department of Pathology and Microbiology
      Omaha, Nebraska, United States
  • 2002–2014
    • University of Nebraska at Omaha
      • • Department of Internal Medicine
      • • Department of Pathology and Microbiology
      Omaha, Nebraska, United States
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2012
    • University of Nebraska at Lincoln
      Lincoln, Nebraska, United States
  • 2011
    • University of Oslo
      Kristiania (historical), Oslo, Norway
    • Columbia University
      New York, New York, United States
  • 2010
    • Ente Ospedaliero Cantonale
      Bellinzona, Ticino, Switzerland
  • 2009
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, Massachusetts, United States
  • 2008
    • Creighton University
      Omaha, Nebraska, United States
  • 2002–2007
    • National Institutes of Health
      • • Center for Cancer Research
      • • Branch of Metabolism
      Bethesda, MD, United States
  • 2006
    • University of Rochester
      • James P. Wilmot Cancer Center
      Rochester, NY, United States
  • 2004
    • Northern Inyo Hospital
      BIH, California, United States
    • University of Texas MD Anderson Cancer Center
      • Department of Leukemia
      Houston, Texas, United States
    • Cornell University
      Итак, New York, United States
  • 2003
    • The Ohio State University
      Columbus, Ohio, United States
    • Duke University
      Durham, North Carolina, United States
  • 1998–2003
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, WI, United States
  • 2001
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 1991
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France