Biomedical subjects

Julie M Vose

Publications and source records attributed to Julie M Vose.

50 records · Page 3Linked to original sources

PubMed2003

Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma: a comparison with allogeneic and autologous transplantation--The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation.

PURPOSE: To compare results of syngeneic, allogeneic, and autologous hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: The databases of the International Bone Marrow Transplant Registry (IBMTR) and the European Group for Blood and Marrow Transplantation were used to identify 89 NHL patients who received syngeneic transplants. These patients were compared with NHL patients identified from the IBMTR and the Autologous Blood and Marrow Transplant Registry who received allogeneic (T-cell depleted and T-cell replete) and autologous (purged and unpurged) transplants. RESULTS: No significant differences in relapse rates were observed when results of allogeneic transplantation were compared with syngeneic transplantation for any histology. T-cell depletion of allografts was not associated with a higher relapse risk, but was associated with improved overall survival for patients with low-grade and intermediate-grade histology. Patients who received unpurged autografts for low-grade NHL had a five-fold (P =.008) greater risk of relapse than recipients of syngeneic transplants, and recipients of unpurged autografts had a two-fold (P =.0009) greater relapse risk than patients who received purged autografts. Among low-grade NHL patients, the use of purging was associated with significantly better disease-free survival (P =.003) and overall survival (P =.04) when compared with patients who received unpurged autografts. CONCLUSION: These analyses failed to find evidence of a graft-versus-lymphoma effect, but do provide indirect evidence to support the hypothesis that tumor contamination may contribute to lymphoma relapse, and that purging may be beneficial for patients undergoing autologous hematopoietic stem-cell transplantation for low-grade NHL.

Adolescent↗

PubMed2003

Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma.

In this article, we report on 904 patients undergoing transplantation for follicular lymphoma. A total of 176 (19%) received allogeneic, 131 (14%) received purged autologous, and 597 (67%) received unpurged autologous transplants. Five-year treatment-related mortality (TRM) rates were 30%, 14%, and 8% and 5-year recurrence rates were 21%, 43%, and 58% after allotransplantation, purged autotransplantation, and unpurged autotransplantation, respectively. In multivariate analyses, allotransplantation had higher TRM and lower disease recurrence. Purged autotransplantation had a 26% lower recurrence risk than unpurged autotransplantation. Five-year probabilities of survival were 51%, 62%, and 55% after allogeneic, purged autotransplantation, and unpurged autotransplantation, respectively. Advanced age, prolonged interval from diagnosis to transplantation, high lactate dehydrogenase (LDH), refractory disease, bone marrow involvement, low performance scores, and transplantation between 1990 and 1993 were associated with adverse outcomes. Total body irradiation was associated with higher TRM but lower recurrence. There was no association between acute or chronic graft-versus-host disease and recurrence after allotransplantation. We conclude that both allogeneic and autologous transplantation can induce durable remissions. There may be a benefit to graft purging in autologous transplantation. The decreased recurrence after allotransplantation is offset by increased TRM. We did not detect a correlation between graft-versus-host disease (GVHD) and recurrence. Finally, outcomes of transplantation for follicular lymphoma show improvement over the past decade.

Adult↗

PubMed2003

Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma.

Mutations have been described in the ataxia telangiectasia mutated (ATM) gene in small numbers of cases of lymphoid neoplasia. However, surveys of the ATM mutation status in lymphoma have been limited due to the large size (62 exons) and complex mutational spectrum of this gene. We have used microarray-based assays with 250,000 oligonucleotides to screen lymphomas from 120 patients for all possible ATM coding and splice junction mutations. The subtypes included were diffuse large B cell, mantle cell, immunoblastic large B cell, follicular, posttransplant lymphoproliferative disorder, and peripheral T cell lymphoma. We found the highest percentage of ATM mutations within the mantle cell (MCL) subtype (43%, 12 of 28 cases), followed by a lower level (10% of cases) in the other subtypes. A frame-shift ATM mutation was found in one peripheral T cell lymphoma patient. In six MCL cases examined, four ATM variants were due to somatic mutation in the tumor cells whereas two others seemed to be germ-line in origin. There was no difference in p53 mutation status in the ATM mutant and wild-type groups of MCL. There was no statistically significant difference in the median overall survival of patients with wild-type vs. mutated ATM in MCL. Additional mutational and functional analyses are needed to determine whether ATM mutations contribute to the development and progression of MCL or are just the consequence of genomic instability in MCL.

Ataxia Telangiectasia Mutated Proteins↗

PubMed2003

Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries.

Mantle cell lymphoma (MCL) has an aggressive clinical course with a median survival < 3 years and is incurable with conventional chemotherapy. A large multicentre study with adequate follow-up may clarify the role of significant factors affecting outcome in autologous stem cell transplantation for MCL. Patients receiving an autologous transplant for MCL between 1988 and 1998, and reported to the European Blood and bone Marrow Transplant (EBMT) registry or Autologous Blood and Marrow Transplant Registry (ABMTR), were included. Expert haematopathology review was required on all identified patients. Disease and transplant details were requested from the transplant centres, and the final cohort of patients with verified pathology, adequate clinical information and follow-up was analysed. One hundred and ninety-five patients were included in the analyses (149 EBMT, 46 ABMTR) with a median follow-up of 3.9 years. The 2 year and 5 year overall survival were 76% and 50%, and progression free survival was 55% and 33% respectively. Disease status at transplant was the most significant factor affecting survival: patients with chemosensitive disease but not in first complete remission (CR1) were 2.99 times (95% CI: 1.66-5.38, P < 0.001) more likely to die than patients transplanted in CR1. Autologous transplantation probably improves survival in patients with MCL especially if performed in first CR.

Adult↗

PubMed2003

Circulating CD20 and CD52 in patients with non-Hodgkin's lymphoma or Hodgkin's disease.

The cell surface proteins CD20 and CD52 differ significantly in their structures and are expressed on the majority of B cells. Both circulating CD20 (cCD20) and circulating CD52 (cCD52) have been recently documented in patients with chronic lymphocytic leukaemia. A retrospective study to establish whether cCD20 and/or cCD52 were detectable in patients with lymphoma, and the clinical associations of these soluble antigens if detected, was conducted. cCD20 and cCD52 levels were analysed in a cohort of 65 patients with non-Hodgkin's lymphoma (NHL) and 37 with Hodgkin's disease (HD). Patients with NHL had elevated pretherapy levels of cCD20 and cCD52 compared with normal individuals. Patients with HD had significantly lower than normal pretherapy levels of both cCD20 and cCD52. cCD20 levels were marginally elevated post-therapy in NHL patients while in patients with HD, cCD20 levels remained significantly lower than normal after therapy. Serum cCD52 levels became significantly lower than normal post-therapy in NHL patients, and remained significantly lower than normal in HD patients. No predictive effects were found for pretherapy or post-therapy levels of cCD52 on survival for either cohort of patients. Post-therapy cCD20 levels independently highly correlated with survival in patients with NHL. Prospective evaluation will be required to establish if cCD20 and cCD52 may be used as biomarkers in the diagnosis, prognostic categorization, and monitoring of the clinical course in patients with lymphoma. The clinical significance of circulating antigen in patients receiving monoclonal antibody therapy directed against CD20 and/or CD52 warrants study.

Adolescent↗

PubMed2003

Establishing an institutional model for the administration of tositumomab and iodine I 131 tositumomab.

Radioimmunotherapy with radiolabeled anti-CD20 antibodies is a promising new treatment approach for low-grade non-Hodgkin's lymphoma. However, the administration of radiolabeled antibodies presents some added complexity. At the University of Nebraska Medical Center (Omaha, NE), an institutional model has been developed that ensures the efficient and safe delivery of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA and GlaxoSmithKline, Philadelphia, PA). An integrated, multidisciplinary treatment team is responsible for managing all aspects of treatment. Using this model, it is possible to administer tositumomab and iodine I 131 tositumomab safely and effectively in the outpatient setting. Patients can usually be released immediately after treatment. Guidelines and instructions for patient release have been developed and validated and are provided herein. These instructions ensure that radiation exposure of family members and caregivers who are exposed to the patient is maintained as low as reasonably achievable and well within regulatory limits.

Antibodies, Monoclonal↗

PubMed2003

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's disease (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, six patients presented with both nodal and extranodal involvement, and five 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 five-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. In conclusion, 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↗

PubMed2002

A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma.

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P =.002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P =.05; and 34% versus 56%, P =.004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%, P =.82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P =.01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P =.09; 44% versus 39%, P =.47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Adolescent↗

PubMed2002

A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival.

Grade 3 follicular lymphoma (FL3) is thought to have an aggressive clinical course. On the basis of possible biologic differences, the new World Health Organization (WHO) classification of lymphoma suggests further subdivision of FL3 into grades 3a and 3b and states that the percentage of involvement by diffuse large B-cell lymphoma (DLBCL) should also be reported. However, the clinical implications of these features are unclear. Therefore, we studied 190 newly diagnosed patients with lymph node-based FL3 who received anthracycline-containing combination chemotherapy. The follicular component was subclassified as grade 3a (FL3a) or grade 3b (FL3b) according to the WHO criteria, or as follicular large cleaved cell type (FLC). The percentage of a diffuse component, if present, was also recorded. Of the 190 cases, there were 107 FL3a (56%), 53 FL3b (28%), and 30 FLC (16%) cases. Diffuse areas were seen in 72 cases (31 FL3a, 28 FL3b, and 13 FLC). There were no significant differences in the clinical characteristics, overall survival, or event-free survival between patients with grades FL3a, FL3b, or FLC. However, those cases with a predominant diffuse component (> 50% diffuse) had a significantly worse overall survival (P =.0037) and event-free survival (P =.012). Therefore, we conclude that the subdivision of FL3 into cytologic subtypes does not appear to be important clinically. However, patients with FL3 having a diffuse component of more than 50% have an inferior survival that is similar to the survival of those with DLBCL.

Adolescent↗

PubMed2002

Autologous transplantation for aggressive non-Hodgkin's lymphoma: results of a randomized trial evaluating graft source and minimal residual disease.

PURPOSE: To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) for aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Of 105 high-risk, persistent, or relapsed NHL patients slated for an autologous HSCT entered onto this trial, 93 eligible patients were randomized to receive cytokine-naive autologous bone marrow transplantation (ABMT) (n = 46) or mobilized peripheral-blood stem-cell transplantation (PBSCT) (n = 47). All patients received carmustine, etoposide, cytarabine, and cyclophosphamide as the conditioning regimen. PBSCT patients also received identical mobilization with granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/d, and both groups received G-CSF 5 microg/kg/d after the infusion of the stem-cell product until neutrophil engraftment. RESULTS: PBSCT patients had significantly faster engraftment of all cell lineages: median time to absolute neutrophil count > or = 500/microL, 10 days versus 13 days on the ABMT arm; median time to platelet count greater than 20,000/microL untransfused, 11 days versus 15 days on the ABMT arm; and median time to RBC transfusion independence, 8 days versus 16 days on the ABMT arm. The complete response rate was 72% for PBSCT and 54% for ABMT. The death rate before posttransplant day 100 was 2% on the ABMT arm and 6% on PBSCT arm. Event-free survival was 37% for PBSCT and 37% for ABMT. However, overall survival for PBSCT was 61% compared with 43% for ABMT. CONCLUSION: Patients with aggressive NHL receiving HSCT randomized to PBSCT demonstrated improved neutrophil engraftment and platelet and RBC transfusion independence. The complete response rate and EFS were not statistically different by randomization arm. Patients whose harvests were positive for minimal residual disease by molecular analysis had poorer EFS.

Adult↗

PubMed2002

Hodgkin's disease in the elderly: improved treatment outcome with a doxorubicin-containing regimen.

PURPOSE: Hodgkin's disease (HD) is a malignancy that displays a bimodal age distribution. Previous reports of treatment in patients greater-than-or-equal 60 years have found a poor outcome, particularly in patients with advanced disease. Because of an improved side-effect profile, the regimen of chlorambucil, vinblastine, procarbazine, and prednisone (ChlVPP) has been proposed for use in elderly patients. PATIENTS AND METHODS: From September 1982 to May 1998, 262 patients with previously untreated HD received either ChlVPP (n = 176) or ChlVPP plus doxorubicin/bleomycin/vincristine (ChlVPP/ABV hybrid; n = 86). Fifty-six patients were greater-than-or-equal 60 years old, and 206 were younger than 60 years. RESULTS: The 5-year overall survival (OS; 87% v 39%) and the 5-year event-free survival (EFS; 75% v 31%) favored patients younger than 60 years of age. Prognostic factors analyzed in patients greater-than-or-equal 60 years of age, other than type of therapy, included sex, stage, Karnofsky performance score, lactic dehydrogenase, number of extranodal sites, B symptoms, size of largest mass, and histologic subtype. In patients older than 60 years, none of the clinical features was a statistically significant predictor of EFS; however, ChlVPP/ABV hybrid was associated with a decreased risk of an event (relative risk, 0.40; 95% confidence interval, 0.19 to 0.83; P =.014) compared with ChlVPP. The 5-year OS for patients greater-than-or-equal 60 years who received ChlVPP was 30%, compared with 67% for those patients receiving the ChlVPP/ABV regimen (P =.0086) CONCLUSION: Patients greater-than-or-equal 60 years with HD who require chemotherapy are better treated with ChlVPP/ABV hybrid than with ChlVPP alone.

Age Factors↗

PubMed2002

CNOP for diffuse aggressive non-Hodgkin's lymphoma: the Nebraska lymphoma study group experience.

The purpose of this study was to evaluate the CNOP regimen (cyclophosphamide, mitoxantrone, vincristine, and prednisone) throughout a community based oncology network with a large number of elderly non-Hodgkin's lymphoma (NHL) patients. Three hundred and seventy-three previously untreated patients with diffuse aggressive NHL received the CNOP regimen administered through a community oncology network, the Nebraska Lymphoma Study Group (NLSG). The complete response rate was 60% with an overall response rate of 73%. The estimated 4-year event-free survival for patients <60years was 44%, compared to 38% for those >age 60 (p = 0.18). However, the 4-year estimated overall survival for patients <60 years was 62% compared to 44% for those >60 years (p < 0.001). Prognostic factors predictive for a poor event-free survival were male gender, stage III/IV disease, Karnofsky score <80, and elevated lactic dehydrogenase (LDH). The lymphoma specific cumulative death rate was 29% for patients <60 years compared with 33% for patients >60 years (p = 0.07). After failing CNOP the 4-year overall survival (OS) was 19%. The estimated 4-year OS for patients who failed CNOP and went on to receive high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplant (ASCT) was 64% for patients < age 60 and 48% for those >60 years (p = 0.23). In conclusion, CNOP chemotherapy administered to patients with diffuse aggressive NHL in a community oncology network produces similar result to that reported for other anthracycline based regimens reported in the literature. Patients >age 60 had a higher rate of failure due to causes other than lymphoma which accounted for a worse survival long-term. However, patients of all ages who failed CNOP and who were able to receive HDC and ASCT demonstrated long-term disease survival after the transplant.

Adolescent↗

PubMed2002

Update on epidemiology and therapeutics for non-Hodgkin's lymphoma.

This chapter presents updated information on the trends and patterns of non-Hodgkin's lymphoma (NHL) diagnoses as well as new information on chemotherapeutic and immunotherapeutic options for NHL treatment. In Section I, Dr. Brian Chiu summarizes the current knowledge regarding the etiologic factors and patterns of NHL as well as suggests future epidemiologic studies based on these preliminary results. In Section II, Dr. Bruce Cheson and colleagues outline new chemotherapeutic and small molecule antineoplastic agents with unique mechanisms of action such as protease inhibitors, farnesyl transferase or histone deacetylase inhibitors, and antisense oligonucleotides. In Section III, Dr. Julie Vose reviews the anti-lymphoma effects of monoclonal antibodies, radioimmunoconjugates, idiotype vaccines, and immunologic enhancing adjuvants with respect to mechanisms of action, clinical trials, and their potential for patient therapy.

Antibodies, Monoclonal↗

PubMedDate not supplied

Combination therapy for non-Hodgkin's lymphoma: an opportunity for pharmaceutical care in a specialty practice.

OBJECTIVE: To describe the application of pharmaceutical care practices in the administration of new therapeutic radiopharmaceuticals used in the treatment of non-Hodgkin's lymphoma (NHL). PRACTICE DESCRIPTION: At the Antibody Labeling Facility at the University of Nebraska Medical Center, the nuclear pharmacist provides support in the formulation, preparation, and quality testing of radiopharmaceuticals. The nuclear pharmacist also provides direct patient care by assisting in the administration of radiopharmaceuticals, monitoring patients during their infusions, and counseling patients on radioimmunotherapy and radiation safety. PRACTICE INNOVATION: Expanding the role of the nuclear pharmacist in treating patients with NHL using radiolabeled monoclonal antibodies (MABs). INTERVENTIONS: The nuclear pharmacist provides specialized pharmaceutical care by being involved in planning patient care, administering diagnostic and therapeutic radiopharmaceuticals, performing individualized patient dose calculations, monitoring patients, and counseling patients. MAIN OUTCOME MEASURES: Number of patients treated with radiolabeled MABs. RESULTS: Since January 1996, 85 patients with NHL have been treated using 131I-tositumomab (Corixa, GlaxoSmithKline), an anti-B1 MAB, under various clinical research protocols requiring specialized pharmaceutical care. The nuclear pharmacist on the team provided direct patient care, assisting with the administration of diagnostic and therapeutic radiopharmaceuticals under a collaborative agreement with a nuclear medicine physician or a radiation oncologist. Other pharmaceutical care activities performed include calculating individual patient doses, obtaining medication histories, counseling patients on their therapy and on radiation safety after early release, and monitoring patients for adverse effects during medication infusion. Patients have responded favorably to nontraditional nuclear pharmacy activities. CONCLUSION: The nuclear pharmacist has become an important member of the health care team that provides a new and unique therapy for patients with NHL. To date, the nuclear pharmacist, in collaboration with the nuclear medicine physician or the radiation oncologist, has successfully administered the tositumomab and 131I-tositumomab combination therapy without significant incident.

Antibodies, Monoclonal↗