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Julie M Vose

Publications and source records attributed to Julie M Vose.

At least 37 records · Page 2Linked to original sources
PubMed2005

Response assessment of aggressive non-Hodgkin's lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography.

PURPOSE: To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS: By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION: Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

Adult↗
PubMed2005

Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab.

The incidence of treatment-related myelodysplastic syndromes and acute myeloid leukemia (tMDSs/tAML) after tositumomab and iodine I(131) tositumomab administration to previously treated and untreated patients with non-Hodgkin lymphoma (NHL) was evaluated. A total of 1071 patients were enrolled in 7 studies: 995 with relapsed/refractory low-grade NHL, +/- transformation (median, 3 prior regimens [range, 1-13 regimens]) and 76 patients with previously untreated low-grade follicular NHL. A single dose of iodine tositumomab and I(131) tositumomab was administered. For tMDS/tAML patients, baseline and posttherapy peripheral blood and marrow specimens were reviewed in a blinded fashion. Median follow-up was 6 years from diagnosis and 2 years from radioimmunotherapy (RIT) for previously treated patients, and 4.6 years from radioimmunotherapy for previously untreated patients. tMDS/tAML was reported in 35 (3.5%) of 995 patients (annualized incidence, 1.6%/y [95% confidence interval, 1.0%-2.0%/y]), and 52% of the tMDS/tAML diagnoses of tMDS/tAML were confirmed in a blinded review (annualized incidence of 1.1%/y [95% confidence interval, 0.7%-1.6%/y]). Of the 25 cases, 10 patients (40%) were diagnosed with tMDS/tAML prior to receiving radioimmunotherapy; 2 (8%) had no pathologic or clinical evidence to support such a diagnosis; and 13 (52%) were confirmed to have developed tMDS/tAML following RIT. This incidence is consistent with that expected on the basis of patients' prior chemotherapy for NHL. With a median follow-up approaching 5 years, no case of tMDS/tAML has been reported in any of the 76 patients receiving iodine I(131) tositumomab as their initial therapy (P = .011 compared with previously treated patients).

Adult↗
PubMed2005

Prognostic factors of chronic graft-versus-host disease after allogeneic blood stem-cell transplantation.

Allogeneic hematopoietic stem cells in peripheral blood transplantation (alloPBSCT) or bone marrow transplantation (alloBMT) have different biological characteristics which may affect differently prognostic factors for incidence and severity of chronic graft-versus-host disease (cGVHD). To determine the prognostic factors of cGVHD in patients receiving alloPBSCT, data on 87 patients who survived at least 100 days after matched related donor myeloablative transplantation were analyzed. Factors significantly associated with higher incidence of cGVHD after alloPBSCT included CMV-positive donor, acute skin GVHD, and diagnoses other than lymphoma. Factors predictive for poor survival following cGVHD diagnosis included platelet count < 100,000/mm3 and history of acute liver GVHD. Acute liver GVHD and etoposide in the preparative regimen significantly increased risk of death due to cGVHD after alloPBSCT. All alloPBSCT multivariate models were fit to an independent cohort of comparable matched related donor alloBMT patients (n=75). After alloBMT, only acute skin GVHD and diagnoses other than lymphoma retained prognostic significance for predicting cGVHD. Low platelet count was the only variable predictive for poor survival in cGVHD patients after alloBMT. Acute liver GVHD was the only factor that retained prognostic significance for risk of death due to cGVHD after alloBMT. These data suggest there are some cGVHD prognostic factors that may be unique to recipients of alloPBSCT. More studies are needed to determine whether cGVHD prognostic systems should be used interchangeably in patient populations receiving different stem-cell products.

Adolescent↗
PubMed2005

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma.

We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-beta), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P = 0.025) or PKC-beta (P = 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-beta had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P = 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-beta was an independent predictor of poor overall survival (P = 0.035). Cyclin D2 and PKC-beta expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.

Adult↗
PubMed2005

Follicular lymphoma: expanding therapeutic options.

The most common indolent lymphoma, follicular lymphoma comprises 35% of adult non-Hodgkin's lymphoma (NHL) in the United States and 22% worldwide. Features associated with adverse outcome include age, male gender, disease stage, and performance status, with the International Prognostic Index being the most widely used risk classification system. Long-term disease-free survival is possible in select patient subgroups after treatment, but very late relapses suggest that quiescent lymphoma cells might be harbored for long periods of time. Radiation therapy is the mainstay of treatment for limited-stage follicular lymphoma, but there is some experience with chemotherapy and combined chemoradiation. When to initiate treatment in patients with advanced disease is controversial, but options include various combined chemotherapy regimens, monoclonal antibodies, radiolabeled antibodies, and bone marrow or stem cell transplantation. Future directions in the treatment of follicular lymphoma include vaccines, antisense therapy, and proteasome inhibitors.

Antibodies, Monoclonal↗
PubMed2004

Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma.

PURPOSE: To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-three patients with chemotherapy-refractory or multiply-relapsed B-cell NHL were treated in a phase I trial combining iodine-131 tositumomab (ranging from 0.30 to 0.75 Gy total-body dose [TBD]) with high-dose BEAM followed by ASCT. RESULTS: The complete response rate after transplantation was 57%, and the overall response rate was 65%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 38 months (range, 27 to 60 months), the overall survival (OS) rate was 55%, and the event-free survival (EFS) rate was 39%. CONCLUSION: There were no significant added toxicities apparent with the addition of iodine-131 tositumomab up to a dose of 0.75 Gy TBD to high-dose BEAM chemotherapy followed by ASCT. The EFS and OS were encouraging in this group of chemotherapy-resistant or refractory B-cell NHL patients. A follow-up phase II trial with iodine-131 tositumomab at the dose of 0.75 Gy TBD with BEAM is currently ongoing.

Adult↗
PubMed2004

Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry.

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

Adolescent↗
PubMed2004

Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma.

Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium ((90)Y; 15 mCi/m(2))/(111)In (5 mCi)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T(1/2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. (90)Y/(111)In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of (90)Y-DOTA-biotin in this format is warranted.

Adult↗
PubMed2004

Prognostic factors influencing survival in patients with B-cell small lymphocytic lymphoma.

The term "B-cell small lymphocytic lymphoma" (B-SLL) is generally reserved for patients with lymph node masses that show the histology and immunophenotype of B-cell chronic lymphocytic leukemia (B-CLL) but who are not leukemic. The aim of our study was to define clinical factors that predict for survival in B-SLL. Thirty-nine patients with B-SLL and with less than 5,000 mature-appearing lymphocytes/microL in the peripheral blood were studied. The median follow-up of survivors was 6.6 years (range, 1.6-12.3 years). The estimated 5-year overall survival (OS) and failure-free survival (FFS) were 66% and 23%, respectively. In the univariate analysis, significant adverse predictors for OS were age > or =60 years, B symptoms, elevated serum LDH, low hemoglobin (<11 g/dL), and high International Prognostic Index (IPI) score (3-5). In multivariate analysis, the IPI score was the only significant predictor of OS. Anemia and B symptoms were additionally predictive of poor OS in patients with low IPI scores.

Adult↗
PubMed2004

Autologous transplantation for diffuse aggressive non-Hodgkin lymphoma in first relapse or second remission.

We evaluated the results of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with diffuse aggressive non-Hodgkin lymphoma (NHL) in first relapse (Rel 1) or second complete remission (CR 2). Data were evaluated from the Autologous Blood and Marrow Transplant Registry on 429 patients with diffuse aggressive NHL who underwent transplantation in Rel 1 or CR 2. Transplantations were performed between 1989 and 1996 and were reported to the Autologous Blood and Marrow Transplant Registry by 93 centers in North and South America. The probability of 3-year survival was 44% (95% confidence interval [CI], 33%-55%). The probability at 3 years of progression-free survival was 31% (95% CI, 27%-36%). Patients who underwent transplantation in CR 2 had a 3-year probability of progression-free survival of 38% (95% CI, 30%-46%) compared with 28% (95% CI, 22%-33%) for those who were not in remission at the time of transplantation (P <.001). In multivariate analysis, chemotherapy resistance, increased lactic dehydrogenase at diagnosis, an interval of <12 months from diagnosis to relapse, age >or=40 years, and use of myeloid growth factors to accelerate posttransplantation bone marrow recovery were adverse predictors of survival. High-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with diffuse aggressive NHL in CR 2 or Rel 1 resulted in better outcome for patients with chemotherapy-sensitive disease, longer relapse-free intervals, and age <40 years. Exposure to myeloid growth factors to accelerate recovery for recipients of bone marrow grafts may increase the risk of disease progression or death.

Adolescent↗
PubMed2004

Graft-versus-host disease: how to translate new insights into new therapeutic strategies.

Graft-versus-host disease occurs when transplanted donor-derived T lymphocytes recognize major or minor histocompatibility complex proteins and their associated peptides expressed by recipient antigen-presenting cells. A widely accepted paradigm for the pathophysiology of acute GVHD is based on the existence of 3 sequential steps: (1) injury to the host environment (as would occur during conditioning regimens); (2) donor T-cell activation, proliferation, and differentiation; and (3) damage to the target tissue caused by either cytotoxicity or indirectly by inflammatory cytokines. In order to reduce the incidence of GVHD, recent studies have focused on methods of prophylaxis as well as novel treatments for established GVHD. We review each phase in the development of acute GVHD and discuss recently developed interventions aimed to prevent or treat GVHD by interfering with these pathways.

Bone Marrow Transplantation↗
PubMed2004

Clinical relevance of circulating angiogenic factors in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma.

Vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and angiogenin are important angiogenic factors. In 65 patients with non-Hodgkin's lymphoma (NHL), pre-treatment VEGF, bFGF, and HGF levels were significantly elevated compared to normal individuals, while angiogenin levels were significantly subnormal. In 37 patients with Hodgkin's disease, pre-treatment levels of VEGF and HGF were significantly elevated, bFGF levels were normal, and angiogenin levels were significantly subnormal. In patients with NHL, post-therapy levels of angiogenin were independently predictive of survival. Both pre-therapy and post-therapy VEGF levels were independently predictive of survival in patients with HD.

Adolescent↗
PubMed2004

BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma.

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32;q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14;18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup.

Apoptosis Regulatory Proteins↗
PubMed2004

Diffuse large B-cell lymphoma arising in nodular lymphocyte predominant Hodgkin lymphoma: a report of 21 cases from the Nebraska Lymphoma Study Group.

We sought to investigate the clinical characteristics and pathologic features and survival outcome of patients with diffuse large B-cell lymphoma (DLBCL) arising in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), since controversy regarding their prognosis exists in the literature. Twenty-one patients with DLBCL arising either concurrently with (n = 7) or subsequent to (n = 14) a diagnosis of NLPHL were identified in the Nebraska Lymphoma Study Group Registry. The clinical and pathologic features of the cases were evaluated, and survival analysis was performed from the time of diagnosis of DLBCL. The median time to the development of DLBCL in those with prior NLPHL was only one year (range, 0.5-24 years). The median age of the patients at the time of diagnosis of DLBCL was 46 years (range, 18-72 years) and the male to female ratio was 17:4. Ten patients presented with nodal DLBCL only, 6 patients presented with both nodal and extranodal involvement, and 5 patients presented with only extranodal DLBCL. Eleven patients had limited stage (I/II) disease and 10 had advanced stage (III/IV) disease. The median overall survival (OS) and failure-free survival (FFS) of the entire group was 35 months and 11 months, respectively, and the predicted 5-year OS and FFS was 31% and 18%, respectively. There were no significant differences in the survival outcomes between patients with DLBCL arising in NLPHL and age- and sex- matched patients with de novo DLBCL. Our findings suggest that patients with DLBCL arising in NLPHL have a prognosis similar to those with de novo DLBCL and should be treated aggressively.

Adolescent↗
PubMed2004

Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin's lymphoma.

PURPOSE: Immunotherapy using monoclonal antibodies to specifically target B cells has provided new hope to many patients with indolent lymphomas, particularly those with chemotherapy-refractory disease. Lymphomas are extremely sensitive to radiation, and significant progress has been made over the last decade in the development of radioimmunotherapy with anti-CD20 antibodies. MATERIALS AND METHODS: Herein we review clinical experience with tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corporation; South San Francisco, CA; and GlaxoSmithKline; Philadelphia, PA) in patients with non-Hodgkin's lymphoma. RESULTS: Therapy with Bexxar has demonstrated high response rates and long durations of response compared with unconjugated anti-CD20 antibodies in patients with relapsed low-grade and transformed low-grade non-Hodgkin's lymphomas. Iodine-131 (I-131) has a long history of clinical experience, an excellent safety record, and favorable nuclear and pharmacologic properties. Importantly, the gamma emissions of iodine-131 facilitate accurate dosimetry to calculate the appropriate patient-specific therapeutic activity to deliver a predetermined total-body dose of radiation, thereby minimizing hematologic toxicity. In clinical trials of Bexxar, objective response rates ranged from 54%-71% in heavily pretreated patients. In the pivotal trial, the number of patients with a longer duration of response after treatment with Bexxar was significantly greater than the number of patients with a longer duration of response after their last qualifying chemotherapy regimen. In 76 newly diagnosed patients, the objective response rate was 97%, and 63% of patients achieved complete responses. CONCLUSION: These data suggest that Bexxar will become an important new option in the treatment of indolent lymphoma.

Antibodies, Monoclonal↗
PubMed2003

Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation.

Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.

Adult↗