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J M Vose

Publications and source records attributed to J M Vose.

At least 73 records · Page 4Linked to original sources
PubMed1996

Phase I/II trial of PIXY321 to enhance engraftment following autologous bone marrow transplantation for lymphoid malignancy.

PURPOSE: A phase I/II study of PIXY321 following high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) was conducted to evaluate the safety and clinical potential of this agent. PATIENTS AND METHODS: Fifty patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) undergoing HDT and ABMT received PIXY321 post-ABMT in doses that ranged from 50 to 1,000 micrograms/m2/d either as intravenous (i.v.) or subcutaneous (SC) dosing until engraftment was reached. RESULTS: If all doses are considered together, the median time to reach an absolute neutrophil count (ANC) > or = 500/microL was 18 days and the median time to platelet transfusion independence was 21 days. At the estimated optimum dose of 750 micrograms/m2/d by SC injection once daily, the median time to reach an ANC > or = 500/microL was 15 days and the median time to platelet transfusion independence was 16 days. Historical control patients who received granulocyte-macrophage colony-stimulating factor (GM-CSF) had a median time to an ANC > or = 500/microL of 19 days and a median time to platelet independence of 26 days. CONCLUSION: The administration of PIXY321 post-ABMT was generally well tolerated and resulted in prompt engraftment in the majority of patients who underwent HDT and ABMT for lymphoid malignancies. The optimum dose and route of administration of PIXY321 suggested by this trial was 750 micrograms/m2/d by once-daily SC injection. Compared with historical control patients who received 2-hour i.v. GM-CSF, patients who received PIXY321 at 750 micrograms/m2/d by SC injection once daily had an improvement in the median days to neutrophil and platelet engraftment by 4 and 10 days, respectively.

Adult↗
PubMed1996

Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease.

PURPOSE: To determine the outcome of HLA-identical sibling bone marrow transplants in advanced Hodgkin's disease. PATIENTS AND METHODS: We reviewed the data on 100 consecutive patients with Hodgkin's disease who received HLA-identical sibling bone marrow transplants between April 1, 1982 and August 12, 1992, reported to the International Bone Marrow Transplant Registry (IBMTR). The median interval from diagnosis to transplant was 2.5 years (range, < 1 to 14). All had advanced disease. Eighty-nine of 100 patients were not in remission at the time of transplant. Fifty had pretransplant Karnofsky scores less than 90% and 27 had active infection in the week before transplant. Patients received a variety of conditioning regimens; 45 received total-body radiation. RESULTS: The 100-day probability of acute graft-versus-host disease (GVHD) was 35% (95% confidence interval [CI], 26% to 46%); the 3-year probability of chronic GVHD was 45% (95% CI, 31% to 59%). The 3-year probability of relapse was 65% (95% CI, 50% to 78%). The 3-year probability of survival was 21% (95% CI, 14% to 30%). The 3-year disease-free survival rate was 15% (95% CI, 9% to 24%). CONCLUSION: HLA-identical sibling bone marrow transplants have a limited role in advanced Hodgkin's disease.

Adolescent↗
PubMed1996

Single-photon emission computed tomography gallium imaging versus computed tomography: predictive value in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma.

PURPOSE: To evaluate the predictive value of computed tomography (CT) scanning and single-photon emission computed tomography (SPECT) gallium (Ga) scanning in the disease-free survival of patients receiving high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred forty-three patients undergoing transplant for NHL underwent CT scanning of chest, abdomen, and pelvis, and a SPECT Ga scan before transplantation and at day + 100 after transplant. The failure-free survival (FFS) by scan result was analyzed. RESULTS: In the diffuse aggressive lymphoma patients, the 1-year FFS for patients having a positive SPECT Ga scan at day + 100 was 15% compared with a 3-year FFS of 47% for those with a negative scan (P < .001). Patients with a positive CT scan at day + 100 had a 36% 3-year FFS, and those with a negative CT scan had a 39% 3-year FFS (P = not significant [NS]). An analysis of the combination of CT scan and SPECT Ga scan results at day + 100 posttransplant demonstrated a 3-year FFS of 14% if they were both abnormal; if the CT was positive and Ga was negative, the 3-year FFS was 68%; positive Ga with a negative CT was 25%; and both negative was 34% (P = .0015). For the patients with follicular NHL, those with a positive SPECT Ga at day + 100 had a 14% 1-year FFS compared with those with a negative scan, who had a 45% 3-year FFS (P < .001). In the follicular NHL patients, the 3-year FFS of those with a positive CT was 17% compared with a 64% 3-year FFS for patients with a negative CT scan (P < .001). CONCLUSION: The use of SPECT Ga scan at day + 100 posttransplant for evaluation of disease activity in patients with diffuse aggressive NHL was highly predictive of eventual outcome and was more predictive than the CT scan results. However, for patients with follicular NHL, the addition of SPECT Ga scanning to CT scanning did not add substantially to the evaluation of transplant outcome.

Adolescent↗
PubMed1996

Phase I trial of recombinant fusion protein PIXY321 for mobilization of peripheral-blood cells.

PURPOSE: Mobilization of peripheral-blood cells (PBC) with cytokines alone results in rapid hematopoietic recovery and avoids the potential morbidity associated with mobilization by chemotherapy. PIXY321, a fusion protein that consists of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), has enhanced hematopoietic colony-forming activity as compared with individual or equimolar combinations of the two cytokines. A phase I trial of PIXY321 for mobilization of PBC in patients with malignant lymphoma was performed. PATIENTS AND METHODS: Thirteen patients with malignant lymphoma who were eligible for high-dose therapy (HDT) were enrolled onto the trial. All patients were ineligible for autologous bone marrow transplantation due to overt metastatic disease in the marrow or to severe marrow hypocellularity. PIXY321 was administered at three dose levels of 250, 500, and 750 micrograms/m2/d by continuous infusion until completion of PBC collections. Collections were initiated when the WBC count was greater than 10 x 10(9)/L or 4 days after the initiation of PIXY321, whichever came first. Collections were continued until a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg patient weight were obtained. RESULTS: PIXY321 was generally well tolerated. Side effects associated with PIXY321 administration did not exceed grade 2 and included fever (85%), chills/sweats (54%), myalgias (38%), fatigue (31%), nausea/vomiting (31%), headache (31%), edema (23%), and rhinorrhea (23%). The median numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the graft products for the three dose levels were 0.31, 2.94, and 2.88 x 10(4)/kg, respectively; the median numbers of burst-forming units-erythroid (BFU-e) were 0.20, 6.94, and 12.78 x 10(4)/kg, and the median numbers of CD34+ cells were 2.30, 0.74, and 0.39 x 10(6)/kg. Following transplantation, the median times to an absolute neutrophil count (ANC) > 0.5 x 10(9)/L were 12, 15, and 12 days, respectively, and the median times to platelet transfusion independence were 30, 19, and 15 days. CONCLUSION: PIXY321 can be safely administered and effectively mobilizes PBC in patients with bone marrow defects. PIXY321-mobilized PBC autotransplants result in rapid and sustained hematopoietic recovery.

Adult↗
PubMed1996

Dose-intensive ifosfamide for the treatment of non-Hodgkin's lymphoma.

Patients with non-Hodgkin's lymphoma (NHL) who either fail to achieve or relapse following an initial complete remission have a poor prognosis with conventional salvage chemotherapy. Patients with chemotherapy-sensitive NHL have a 45% chance of long-term disease-free survival with high-dose chemotherapy and autologous bone marrow transplantation (ABMT). Patients with chemotherapy-resistant NHL have a significantly reduced chance of long-term disease-free survival. Ifosfamide, a synthetic analogue of cyclophosphamide, has been evaluated in a few small trials of high-dose chemotherapy and ABMT in lymphoma. Because of their clinical synergy, ifosfamide has been combined with carboplatin and etoposide (ICE) and given with ABMT in several phase I/II dose-escalating studies. Maximum tolerated doses of the ICE regimen in these trials are 16 to 20.1 g/m2 ifosfamide, 1.8 g/m2 carboplatin, and 1.2 to 3.0 g/m2 etoposide. Renal, central nervous system, and cardiac toxicities have precluded further dose escalation. Sequential dosing protocols, administration of high-dose chemotherapy with peripheral blood progenitor cell support, and other approaches, possibly combining current treatment options, may be necessary to further improve the long-term survival of patients with relapsed NHL.

Antineoplastic Agents↗
PubMed1996

Cardiopulmonary function and autologous bone marrow transplantation: results and predictive value for respiratory failure and mortality. The University of Nebraska Medical Center Bone Marrow Transplantation Pulmonary Study Group.

Cardiopulmonary complications are a major cause of morbidity and mortality in patients undergoing high-dose therapy with stem cell transplant support. Since exercise tolerance testing (ETT) assesses the cardiopulmonary reserve of an individual, we hypothesized that ETT performed prior to transplant would predict respiratory failure and mortality and would be a superior predictor over resting cardiopulmonary function tests. We performed a retrospective study of 191 lymphoma patients who underwent ETT prior to transplant between 1 June 1990 and 31 December 1992 and compared the results of ETT with resting pulmonary function tests (PFT) and resting cardiac ejection fraction (EF). ETT revealed that cardiac, pulmonary and combined cardiopulmonary limitation were observed in 31, 20 and 16% of the patients, respectively, with a gas diffusion-type limitation being the most common exercise limitation. Resting PFT were abnormal in 58% of patients with a diffusion defect being the most common abnormality. Low EF was observed in 6.8% of patients. Twelve patients eventually required mechanical ventilation post-transplant with only the resting diffusion PFT predictive of this complication. There were five early deaths that were attributable to respiratory failure and neither resting nor ETT studies were predictive of these deaths. ETT and EF performed prior to transplant in lymphoma patients undergoing autologous transplant do not predict for either respiratory failure or short-term mortality. Our findings may be due to the rather low incidence of respiratory failure (6.3%) and low early mortality from cardiopulmonary complications (2.6%) seen in our patient population.

Adolescent↗
PubMed1996

Use of continuous infusion granulocyte-macrophage colony-stimulating factor alone or followed by granulocyte colony-stimulating factor to enhance engraftment following high-dose chemotherapy and autologous bone marrow transplantation for lymphoid malignancies.

We evaluated the differences in engraftment and toxicities post-autologous transplant using granulocyte-macrophage colony stimulating factor (GM-CSF) as a continuous infusion either alone or in a sequential manner with granulocyte colony-stimulating factor (G-CSF). Patients receiving high-dose chemotherapy and autologous bone marrow transplantation (ABMT) for lymphoid malignancies participated in two phase II trials evaluating either continuous infusion GM-CSF (GM-CSF (CI)) or continuous infusion GM-CSF followed by sequential G-CSF (GM-CSF/G-CSF) administered post-ABMT. These patients were compared to similar historical control patients receiving GM-CSF administered as a 2-h intravenous (i.v.) infusion (GM-CSF (2-h)). Patients receiving GM-CSF (CI) and GM-CSF/G-CSF had a median day to reach an absolute neutrophil count of 500/microliter post-ABMT of 12 and 11 days, respectively. This compared to a median day of 22 in the GM-CSF (2-h) historical control patients. The median day to platelet independence was 18, 18 and 30 days, respectively. The incidence of toxicities such as incidence of infection, pleural effusions, and rash did not differ greatly between the groups. We conclude that the use of continuous infusion GM-CSF either alone or sequentially with G-CSF produced improved engraftment times compared to historical control patients treated with GM-CSF as a 2-h i.v. infusion. The toxicities at a reduced dose of 125 micrograms/m2 given as a continuous infusion appear to be similar to those seen in patients receiving GM-CSF as a 2-h infusion.

Adult↗
PubMed1995

Multiple organ dysfunction syndrome in bone marrow transplantation.

OBJECTIVE: To define the frequency and outcome of organ dysfunction in bone marrow transplantation (BMT) and to determine if patients with organ dysfunction have lower levels of protein C (PC) and/or antithrombin III (ATIII) than those without organ dysfunction. DESIGN: Inception cohort of patients undergoing BMT, followed for 28 days, until hospital dismissal, or until death. SETTING: Bone marrow transplant department of a university hospital. PATIENTS: A total of 199 consecutive patients admitted for BMT. INTERVENTIONS: Standard supportive care was given to all patients. MAIN OUTCOME MEASURES: Definitions of organ dysfunction were arrived at prior to beginning the study. They include pulmonary, central nervous system (CNS), hepatic, and renal dysfunction. Protein C and ATIII levels were measured prior to beginning the preparative regimen and weekly thereafter. RESULTS: Single organ dysfunction, manifesting as pulmonary, CNS, or hepatic dysfunction, occurred in 93 (48.5%) of the 199 patients and was a strong predictor of multiple organ dysfunction syndrome (MODS) and death. Death occurred in 14 (7.0%) of the patients. Cause of death was precisely identified in only four patients. Low levels of either PC or ATIII were associated with death and pulmonary, CNS, and hepatic dysfunction. Multivariate analysis showed ATIII and PC levels were associated with single organ dysfunction independent of the type of transplant, the type of preparative regimen, and the presence of bacteremia. CONCLUSIONS: Single organ dysfunction during BMT is a marker for a systemic abnormality that has a high likelihood of progressing to MODS, similar to that seen in other critically ill patient populations. MODS is the leading cause of death in series of BMT patients. Low levels of ATIII and PC are markers of and may be involved in the pathogenesis of MODS in BMT.

Adolescent↗
PubMed1995

Prognostic value of cellular proliferation and histologic grade in follicular lymphoma.

The clinical usefulness of histologic grading in follicular lymphoma (FL) is controversial and is further compromised by the subjective nature and poor reproducibility of most systems in current use. Therefore, we decided to objectively evaluate the importance of cellular proliferation in FL, along with the current grading systems. We studied 106 patients with FL who were uniformly staged and aggressively treated. A proliferative index (PI) was determined quantitatively using an automated image analyzer and a new Ki-67 antibody that stains archival paraffin tissues. The cases were also subclassified according to the Berard, Rappaport, Luke-Collins, and Jaffe methods, and survival analysis was performed. Patients with a low PI (< 40%) had a significantly longer overall survival (OS) than those with a high PI (> or = 40%), but the PI did not predict failure-free survival (FFS). The mean PI correlated well with the subgroups in each of the various classifications. All four of the classification methods were predictive of OS, but only the Berard method appeared to predict FFS and suggest that a proportion of patients with FL may be curable. In multivariate analysis, histologic classification was the only independent predictor of OS (Berard method: relative risk, 3.1) and the International Prognostic Index was the only independent predictor of FFS (relative risk, 2.3). We conclude that the Berard method for grading of FL is clinically useful and, along with the International Prognostic Index, should be included in future clinical studies of FL. The measurement of cellular proliferation does not appear to add additional useful information in FL.

Adult↗
PubMed1995

Granulocyte-macrophage colony-stimulating factor as adjunct therapy in relapsed lymphoid malignancy: implications for economic analyses of phase III clinical trials.

With the increasing concern over the high cost of health care, policy makers have incorporated economic analyses into phase III clinical trials as the randomized clinical trials can provide important information on the efficacy and potential cost-effectiveness of new pharmaceutical agents. Economic analyses of single-hospital experience during phase III trials of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy for high dose chemotherapy with autologous stem cell support found significant shortening of neutropenia with GM-CSF at each hospital, but shortened hospitalization (and lower costs) at only two of three hospitals. In this study, we added data from three additional hospitals and found that the 103 patients who received GM-CSF had, on average, 5.7 days shorter durations of severe neutropenia than the 95 patients who received placebo (p < 0.0001) and 3.4 days shorter in hospitalization (p = 0.06). However, the duration of hospitalization, the primary determinant of health care costs, was shorter for GM-CSF patients in only four of the six centers and the duration of hospitalization of placebo patients was shorter at the other two centers. Careful analyses must be carried out when phase III clinical trial results are used to derive estimates of cost-effectiveness of new pharmaceutical agents. The interpretation of economic analyses of phase III clinical trials raises issues related to the perspective of the investigators, study design, collection of data on resource utilization, learning curve effects and generalizability of the results to other settings.

Antineoplastic Agents↗
PubMed1995

Comparison of subcutaneous and intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor for peripheral blood stem cell mobilization.

In an effort to determine whether subcutaneous or continuous intravenous infusion administration of rhGM-CSF results in better hematopoietic progenitor mobilization, the findings of two sequential clinical trials were reviewed. Patients who had received prior chemotherapy for leukemia, lymphoma, multiple myeloma, breast cancer, or other solid tumors and were candidates for high-dose therapy received rhGM-CSF, 250 micrograms/m2/day, either as a continuous intravenous infusion (trial 1) or subcutaneously (trial 2) for stem cell mobilization. At least five apheresis collection procedures were performed to collect a target number of 6.5 x 10(8) mononuclear cells (MNC)/kg. For the 37 patients in trial 1, the collections contained a median of 7.99 x 10(8) MNC/L (range 6.42-21.36) and a median of 5.27 x 10(4) CFU-GM/kg (range 0.28-19.35). In trial 1, 25 patients were autografted with their cells and recovered 0.5 x 10(9) granulocytes/L at a median of 12 days (range 6-16). For the 33 patients in trial 2, the autograft product contained a median of 7.63 x 10(8) MNC/kg (range 6.51-22.66) and 6.31 x 10(4) CFU-GM/kg (range 0.06-60.4). In trial 2, 25 patients were autografted. The median time to reach 0.5 x 10(9) granulocytes/L was 11 days (range 9-26). All patients received rhGM-CSF after peripheral stem cell transplant. No significant differences in the collected products or the time to hematopoietic recovery was found between the two trials (p > 0.05). The mobilization effects of subcutaneous rhGM-CSF in these pretreated patients were similar to those of intravenous rhGM-CSF.

Adult↗
PubMed1995

The role of high-dose therapy and autologous hematopoietic stem cell transplantation for mantle cell lymphoma.

BACKGROUND: Although mantle cell lymphoma (MCL) is a distinct disease entity with well described clinical and pathological features, little information exists regarding its therapy. This paper will evaluate patients with MCL receiving either induction therapy with an anthracycline or high-dose chemotherapy and autologous hematopoietic stem cell transplantation for relapsed disease. PATIENTS AND METHODS: The cases of 14 previously untreated patients with MCL who received an anthracycline-containing combination chemotherapy regimen on Nebraska Lymphoma Study Group protocols from 3/83 to 2/92 were reviewed. During the same time period, a different set of nine patients with recurrent MCL were referred for high-dose chemoradiotherapy and autologous stem cell rescue as salvage therapy. RESULTS: The five year overall (OS) and failure-free (FFS) survivals from the initiation of chemotherapy for the patients receiving an induction therapy with an anthracycline containing regimen were 23% and 8%, respectively. At the time of this analysis, three of the nine transplant patients remain progression-free 7, 12, and 25 months post-transplant. Two year overall and FFS for all nine patients was 34%. CONCLUSIONS: Longer follow-up of greater patient numbers is required to determine whether high-dose therapy can overcome the chemoresistance and increase the cure rate of MCL. Since most patients with this disease have minimal chance of cure with standard chemotherapy, the optimal timing for high dose therapy may be as part of front-line treatment. Further clinical trials are required to investigate the potential benefits of high-dose therapy for patients with MCL.

Aged↗
PubMed1995

Clinical applications of hematopoietic growth factors.

PURPOSE AND DESIGN: To review the current clinical uses, ongoing investigations, and future applications of hematopoietic growth factors. Approved cytokines, as well as cytokines not yet released for general use, are included in this review. RESULTS: Clinical applications of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin, the three recombinant hematopoietic growth factors currently commercially available for clinical use in the United States, are discussed. Macrophage colony-stimulating factor (M-CSF), interleukin-3 (IL-3), PIXY321, stem-cell factor (SCF), IL-1, IL-6, and IL-11 represent cytokines not yet approved; the majority of these newer agents have their principal action at an earlier time point in the hematopoietic cascade than the currently approved cytokines. Current clinical uses of hematopoietic growth factors include decreasing cytopenias associated with chemotherapy, those due to congenital or acquired bone marrow failure states, those that occur after high-dose chemotherapy and bone marrow transplantation, peripheral-blood progenitor mobilization, and supportive care of leukemia patients. CONCLUSION: Hematopoietic growth factors have made a significant impact on the prevention of infections associated with chemotherapy-induced neutropenia, shortening of neutropenia following high-dose chemotherapy and progenitor-cell transplantation, and chemotherapy-associated anemia. Cost-effectiveness and cost-benefit analyses in future phase III and pharmacologic studies will aid in the assessment of these agents.

Antineoplastic Agents↗
PubMed1995

Costs of care and outcomes for high-dose therapy and autologous transplantation for lymphoid malignancies: results from the University of Nebraska 1987 through 1991.

PURPOSE AND METHODS: High-dose therapy with autologous stem-cell support has become common treatment for relapsed or refractory lymphomas. We conducted a study of 178 patients with Hodgkin's disease and 149 patients with non-Hodgkin's lymphoma who received high-dose therapy with stem-cell support. We evaluated the following: (1) whether improvements in outcomes over time found for surgical procedures were also true for a new nonsurgical procedure, autologous bone marrow and peripheral stem-cell transplantation; and (2) whether such a relationship, if it existed, applied to both clinical and economic outcomes. RESULTS: Mortality rates for patients with Hodgkin's disease decreased from 20% in 1987 to 0% in 1991. For non-Hodgkin's lymphoma, the mortality rate decreased from 29% in 1987 to 4% in 1991. Multivariate analyses indicated that the number of previous transplants was the most important factor associated with survival and low-cost care. After controlling for differences in clinical factors, a logistic regression model predicted that patients with Hodgkin's disease had a 20% chance of dying after 30 cases and a 5% chance after 178 cases; patients with non-Hodgkin's disease had a 33% chance of dying after 14 cases and a 5% chance after 149 cases. For patients with Hodgkin's disease, the cost decreased at a rate of 10% per year from 1987 to 1991 (P = .001), while for patients with non-Hodgkin's lymphoma, the cost of transplants decreased at a rate of 8% per year. CONCLUSION: Survival rates improved and costs of care decreased over time for patients who received high-dose therapy with stem-cell support. These changes are most likely related to improvements in supportive care technologies, better patient selection, and experience of the transplant team.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Clinical and prognostic significance of bone marrow involvement in patients with diffuse aggressive B-cell lymphoma.

PURPOSE: We studied the effect of morphology and extent of bone marrow (BM) infiltrate on the survival of patients with diffuse aggressive B-cell non-Hodgkin's lymphoma (NHL), along with clinical features. PATIENTS AND METHODS: Sixty adult patients with diffuse aggressive B-cell NHL and BM involvement at the time of presentation were studied. All patients were uniformly staged and treated with a curative high-dose chemotherapy regimen. BM involvement was assessed according to the cytology, pattern of infiltration, and extent of involvement, and was correlated with overall survival (OS) and failure-free survival (FFS). RESULTS: Patients with BM involvement that consisted of > or = 50% large cells or BM involvement of > or = 70% had a poorer OS (P = .065 and P = .055, respectively). Those who presented with an infiltrate of less than 50% large cells and an international prognostic index (IPI) of < or = 3 had a significantly longer postrelapse survival time (P = .003). A diffuse or interstitial pattern of BM involvement was predictive of both poor OS and FFS (P = .008 and .009, respectively). Multivariate analysis indicated that only IPI (P = .0005) and pattern of BM infiltration (P = .009) were independent predictors of OS, and only the former was predictive of FFS (P = .03). CONCLUSION: The IPI is predictive of OS and FFS, while BM involvement with a diffuse or interstitial pattern is associated with significantly poorer OS. Patients with BM infiltration that involved > or = 70% of the marrow or contained > or = 50% large cells had poor OS, but more patients need to be studied to determine the significance. Two parameters, IPI < or = 3 and BM large cells less than 50%, identify a group of patients with long-term survival after relapse.

Adult↗