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J M Vose

Publications and source records attributed to J M Vose.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of monocyte-dependent T cell inhibitory activity in GM-CSF vs G-CSF mobilized PSC products.

This study compares the immune properties of peripheral blood stem cell (PSC) products mobilized with different hematopoietic growth factors (HGFs) as well as apheresis products and peripheral blood leukocytes (PBL) from normal individuals. We found that monocytes in mobilized PSC products appear to inhibit T cell function independent of whether granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for mobilization. In addition, the GF used to mobilize the stem cell product may be less important to the CD4:CD8 ratio than the extent of prior chemotherapy, as we found an inverse correlation between chemotherapy and the CD4:CD8 ratio. In other observations, all apheresis products, whether mobilized or unmobilized, contained significantly more monocytes compared to normal PBL. The mononuclear cells (MNC) from G-CSF or GM-CSF mobilized PSC products had a similar T cell phytohemagglutinin (PHA) mitogenic response that was significantly lower (P = 0.001 and P = 0.005, respectively) than non-mobilized apheresis products. We also examined the T cell inhibitor (TI) activity of the MNC from the PSC products for allogeneic lymphocyte proliferation and found that PSC products significantly reduced the proliferation of allogeneic PBL to PHA. A significant correlation (P = 0.001, r = 0.517) between the frequency of monocytes and TI activity also was observed.

Adult↗
PubMed1999

Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy.

Adolescent↗
PubMed1999

Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group.

PURPOSE: To investigate whether primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathologic entity with a more aggressive course than other diffuse large B-cell lymphomas (DLBL). MATERIALS AND METHODS: All patients with CD20-positive DLBL who presented with a mediastinal mass measuring at least 5.0 cm and were treated with curative intent were identified. A control group of 352 patients with nonmediastinal DLBL was selected for comparison. RESULTS: The 43 patients with PMLBL had a male to female ratio of 20:23 and a median age of 42 years. Stage I/II disease was present in 58% of the patients, with only 9% having bone marrow involvement. A complete remission was achieved in 63% of the patients, and the 5-year overall and failure-free survivals were 46% and 38%, respectively. Among the clinical variables, an elevated serum lactate dehydrogenase level, a low performance score, more than one extranodal site, and an intermediate or high International Prognostic Index score were predictive of poor survival. When compared with the DLBL group, a younger median age was the only clinical feature that was significantly different in the PMLBL group. CONCLUSION: The clinical features of PMLBL do not appear to be significantly different from those of nonmediastinal DLBL. Although the younger age of onset, slight female predominance, mediastinal location, and size of the mass may justify the recognition of PMLBL as a clinical syndrome, additional evidence is needed to define it as a distinct disease entity.

Adolescent↗
PubMed1999

Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin's disease in children and adolescents.

PURPOSE: To determine the treatment outcome and clinical factors that are of prognostic significance for children and adolescents with relapsed or refractory Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Fifty-three consecutive children and adolescents 21 years of age or younger with relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after transplantation, 29 patients (55%) were in a complete remission or maintained a continuous complete response, six (11%) had a partial response, and 11 (21%) failed to respond or had progressive disease. The failure-free survival (FFS) at 5 years was 31%, and overall survival was 43%. Twenty-one patients died of progressive HD, and nine died secondary to transplantation-related complications, including two secondary leukemias. Prognostic factors important for FFS were normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%), compared with patients with elevated LDH levels (5-year FFS = 0%) (P < .001), and disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There was no statistically significant difference in FFS or overall survival between age subgroups that were analyzed (< 13, 13 to 18, 19 to 21) or in comparison with an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can result in long-term cures and should be considered for children and adolescents with relapsed HD.

Adolescent↗
PubMed1998

Allogeneic bone marrow transplantation for low-grade lymphoma.

Advanced low-grade lymphomas are usually incurable with conventional-dose chemotherapy. It is uncertain whether cures are possible with high-dose therapy and bone marrow transplant from a human leukocyte antigen (HLA)-identical sibling. We sought to determine the outcome of HLA-identical sibling bone marrow transplants in advanced low-grade lymphoma in an observational study of 113 patients conducted at 50 centers participating in the International Bone Marrow Transplant Registry (IBMTR). The median patient age was 38 years (range, 15 to 61). Eighty percent had stage IV disease at the time of transplantation. The median number of prior chemotherapy regimens was two (range, 0 to 5). Thirty-eight percent had refractory disease and 29% a Karnofsky performance score (KPS) less than 80%. All patients underwent allogeneic bone marrow transplantation from a HLA-identical sibling donor. The conditioning regimen included total-body irradiation (TBI) in 82% of patients; cyclosporine was used for graft-versus-host disease prophylaxis in 74%. Survival, disease-free survival, recurrence rate, treatment-related mortality, and causes of death were determined. Three-year probabilities of recurrence, survival, and disease-free survival were 16% (95% confidence interval [CI], 9% to 27%), 49% (95% CI, 39% to 60%), and 49% (95% CI, 39% to 59%), respectively. Higher survival was associated with pretransplant KPS >/=90%, chemotherapy-sensitive disease, use of a TBI-containing conditioning regimen, and age less than 40 years. We conclude that high-dose therapy followed by transplantation from a HLA-identical sibling leads to prolonged survival in some patients with advanced low-grade lymphoma. Most mortality is treatment-related, and recurrences are rare.

Adolescent↗
PubMed1998

A multicenter study of platelet recovery and utilization in patients after myeloablative therapy and hematopoietic stem cell transplantation.

An observational study was conducted at 18 transplant centers in the United States and Canada to characterize the platelet recovery of patients receiving myeloablative therapy and stem cell transplantation and to determine the clinical variables influencing recovery, determine platelet utilization and cost, and incidence of hemorrhagic events. The study included 789 evaluable patients transplanted in 1995. Clinical, laboratory, and outcome data were obtained from the medical records. Variables associated with accelerated recovery in multivariate models included (1) higher CD34 count; (2) higher platelet count at the start of myeloablative therapy; (3) graft from an HLA-identical sibling donor; and (4) prior stem cell transplant. Variables associated with delayed recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic veno-occlusive disease; and (4) use of posttransplant growth factors. Disease type also influenced recovery. Recipients of peripheral blood stem cells (PBSC) had faster recovery and fewer platelet transfusion days than recipients of bone marrow (BM). The estimated average 60-day platelet transfusion cost per patient was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was found that 11% of all patients had a significant hemorrhagic event during the first 60 days posttransplant, contributing to death in 2% of patients. In conclusion, clinical variables influencing platelet recovery should be considered in the design and interpretation of clinical strategies to accelerate recovery. Enhancing platelet recovery is not likely to have a significant impact on 60-day mortality but could significantly decrease health care costs and potentially improve patient quality of life.

Antigens, CD34↗
PubMed1998

High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

BACKGROUND: High-dose therapy followed by autologous stem-cell transplantation (autoSCT) induces complete remissions in the majority of patients with advanced B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma (B-CLL). However, the long-term utility of this therapy for B-CLL is unknown. PATIENTS AND METHODS: Sixteen previously treated patients with B-CLL were transplanted using autologous blood (n = 13) or bone marrow (n = 3). The median age of the patients was 49 f1p4s (range 44-60 years), and the median number of prior chemotherapy regimens was two. Patients were eligible for transplantation if they had chemosensitive disease and no morphologic evidence of malignant cells in the graft. Preparative regimens included cyclophosphamide and total-body-irradiation, with or without cytarabine, or BEAC. RESULTS: All patients engrafted and achieved a complete remission posttransplant. Ten patients were alive at a median of 41 months (range 22-125 months), and five were disease-free. Eight patients have relapsed and six have died (three from progressive malignancy). The projected three-year overall survival, failure-free survival and relapse rates were 68%, 37%, and 56%, respectively. CONCLUSIONS: AutoSCT for advanced B-CLL is associated with a high relapse rate. Whether this therapy can prolong life or produce cures is uncertain.

Adult↗
PubMed1998

Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.

Forty-one patients were studied at set times after allogeneic blood stem cell transplantation (alloBSCT) for recovery of lymphocyte numbers and function. Cells were mobilized with G-CSF from HLA-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate; G-CSF was administered post-transplant. Median time to absolute lymphocyte count (ALC) >500/microl was 17 days vs 41 and 49 days in historical alloBMT patients with G-CSF (n = 23) or no cytokine (n = 29) post-transplant, respectively (P < 0.0001). CD4/CD8+ ratio was 1.9 on day 28 after alloBSCT, then gradually declined to 0.8 at 1 year due to more rapid CD8+ cell recovery. Mean phytohemagglutinin-induced T cell responses were lower than normal on day +28 (P < 0.05), then tended to recover towards normal values. Natural-killer cytotoxicity remained low from day +28 to 1 year post-alloBSCT, but considerable lymphokine-activated killer cytotoxicity was induced from cells already obtained on day +28. Faster lymphocyte recovery correlated with better survival in alloBSCT patients (median follow-up 287 days, P = 0.002), ALC recovery was not affected by acute GVHD, CMV infections or doses of infused cells. ALC recovery did not correlate with survival in either historical alloBMT group. These data suggest that after alloBSCT lymphocyte reconstitution is faster than after alloBMT, and that quicker lymphocyte recovery predicts better survival in the alloBSCT setting.

Adult↗
PubMed1998

Epstein-Barr virus-associated lymphoproliferative disorder after autologous bone marrow transplantation: report of two cases.

Epstein-Barr virus-associated lymphoproliferative disorders have been frequently reported as a complication of solid organ and allogeneic bone marrow transplantation. Their occurrence is rare after autologous bone marrow transplantation (BMT) with only five published reports in the literature. We report two cases of post-transplant lymphoproliferative disorder occurring after autologous BMT for Hodgkin's disease and non-Hodgkin's lymphoma. Post-transplant lymphoproliferative disorders can occur after autologous BMT and should be included in the differential diagnosis of patients with persistent fever, adenopathy or pulmonary infiltrates.

Adult↗
PubMed1998

High-dose chemotherapy and hematopoietic stem cell transplantation for relapsed or refractory diffuse large-cell non-Hodgkin's lymphoma.

The use of high-dose chemotherapy and transplantation for chemotherapy sensitive relapsed diffuse large-cell non-Hodgkin's lymphoma is now the gold standard for patients who are candidates for such therapy. Recent data also demonstrates the relative effectiveness of this approach for patients who are induction failures but are continuing to respond to conventional therapy at the time of transplantation. Newer approaches such as the use of novel agents to modify the transplant regimen, newer cytokines, or alternative sources of hematopoietic stem cells need to be tested in order to improve the outcome in patients with chemotherapy resistant disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Effect of follicularity on autologous transplantation for large-cell non-Hodgkin's lymphoma.

PURPOSE: This study evaluated the outcomes of patients who received high-dose chemotherapy (HDC) and autologous hematopoietic stem-cell transplantation (ASCT) for large-cell non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a diffuse histology. PATIENTS AND METHODS: The prognostic factors in 289 patients who underwent HDC and ASCT for large-cell NHL between May 1983 and December 1996 were analyzed. RESULTS: With a median follow-up duration of 24 months for surviving patients (range, 3 to 131 months), 112 of 289 (39%) were alive and 82 of 289 (28%) were failure-free. In a multivariate analysis, the factors associated with a poorer failure-free survival (FFS) included a lactic dehydrogenase (LDH) level greater than normal (P < .0001), three or more prior chemotherapy regimens received (P < .01), a mass > or = 10 cm at transplant (P < .01), and diffuse histology at the time of transplant (P = .026). Patients who received HDC and ASCT for large-cell NHL in the good-prognosis category (normal LDH, < three prior chemotherapy regimens, no large mass, and not chemotherapy-resistant) had a 5-year survival rate of 45%. Within the good-prognosis group, patients with diffuse large-cell NHL had a 5-year survival rate of 42% compared with 58% for patients with follicular large-cell (FLC) lymphoma (P = .05). CONCLUSION: Good-prognosis patients with FLC histology who receive HDC and ASCT have an improved survival compared with good-prognosis patients with a diffuse large-cell histology.

Adolescent↗
PubMed1998

Lymphoma cells associated with bone marrow stromal cells in culture exhibit altered growth and survival.

The detection of clonal populations of lymphoma cells in histologically negative bone marrow using culture techniques is a predictor of poor outcome for patients undergoing high dose therapy and autologous transplantation. In positive cultures, lymphoma cells were observed as outgrowths in association with adherent stromal cells, whilst only stromal cells were observed in negative long-term cultures. This study developed an experimental model to further study the interactions occurring between lymphoma cells and stromal cells. Using random dot graticule analysis, 86% and 74%, respectively, of patient lymphoma cells grew in association with stromal cells in leukapheresis and bone marrow harvest cultures with the formation of cobblestone areas at sites of interaction between lymphoma cells and stromal cells. Secondary cultures showed that individual stromal cells were able to support the growth of a small number of lymphoma cells. Coculture of the human lymphoma cell lines with a murine bone marrow stromal cell line, MS-5 also resulted in the formation of cobblestone areas, which corresponded with the suppression of nonadherent cell production by the lymphoma cell lines. Upon interacting with MS-5 cells, the lymphoma cell lines formed pseudopodia and underwent pleiomorphic nuclear changes. Contiguous linear homotypic associations between lymphoma cells were evident, as opposed to focal contacts occurring in the heterotypic interactions between lymphoma cells and MS-5 cells. An increasing proportion of supernatant lymphoma cells underwent apoptosis as time in culture increased. These results demonstrate that bone marrow stromal cells alter the pattern of growth of lymphoma cells and may have an important role in the maintenance of occult lymphoma by inhibiting apoptosis.

Apoptosis↗
PubMed1998

Current approaches to the management of non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) is a complex malignancy with many different clinical presentations, histologies, and varied treatment options depending on the histologic type and other prognostic factors. This article focuses on the major histologic subtypes of NHL with discussion of the natural history of each and information on various treatment options.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Rapid immunologic reconstitution following transplantation with mobilized peripheral blood stem cells as compared to bone marrow.

A majority of patients with intermediate or high-grade non-Hodgkin's lymphoma (NHL) who are treated with high-dose chemotherapy (HDT) and hematopoietic stem cell transplantation subsequently relapse. Until recently, transplantation was associated with high morbidity and mortality and the focus was on improving the safety of this procedure. However, the use of growth factors and other supportive measures has successfully reduced treatment mortality to less than 5%. Therefore, new strategies need to be developed to eliminate the growth of any occult tumor cells reinfused with the stem cell products and the tumor cells remaining in the patient. One approach is to improve the immune function of the patients by a more rapid immune reconstitution and augmentation of effector cell function. We report studies comparing immune recovery following HDT and autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT). These studies examined patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) who were treated with HDT and PSCT (n = 56) or ABMT (n = 60). The PSCT patients had a significantly faster recovery of circulating monocytes (CD14+ cells), natural killer ((NK) CD56+) cells, T helper (CD4+) cells, TCR gamma/delta cells, and naive T lymphocytes (CD45RA+). Following ABMT there was a significantly more rapid increase in the frequency of T suppressor/effector (CD8+) cells, B (CD19+) cells, CD34+ cells, polymorphonuclear leukocytes (PMN) and memory T lymphocytes (CD45RO+). The CD4:CD8 and CD45RA:CD45RO ratios were consistently higher in the PSCT group as compared to ABMT suggesting an improved ratio of T helper to T effector/suppressor cells and naive T cells. The differences in cellular phenotype translated into improved T cell function (PHA mitogenesis) and T cell help (pokeweed mitogenesis). In addition, there as an accelerated reconstitution of NK cell activity following PSCT as compared to ABMT. The more rapid reconstitution of NK and T cells in patients rescued with PSCT as compared to ABMT may contribute to an improved clinical outcome. Further, patients receiving a PSCT may be more responsive to adjuvant immunotherapy following transplantation.

Adult↗
PubMed1997

High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin's lymphoma.

PURPOSE: This study evaluated the results of high-dose therapy followed by autologous bone marrow or peripheral-blood stem-cell transplantation for patients with follicular low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: We performed a retrospective review of 100 patients undergoing autologous transplantation for follicular low-grade lymphoma between April 22, 1983 and December 31, 1993. RESULTS: Sixty-seven patients remained alive and 48 were failure-free. The median follow-up duration of surviving patients was 2.6 years (range, 1.0 to 11.7). There were eight (8%) deaths within 100 days of transplantation. Six additional patients died of nonrelapse causes up to 912 days after transplantation. Overall survival at 4 years was estimated to be 65% (95% confidence interval [CI], 54% to 75%) and failure-free survival was estimated to be 44% (95% CI, 33% to 55%). There was no definite evidence of a plateau in the failure-free survival curve. The only factor significantly associated with overall survival and failure-free survival was the number of chemotherapy regimen received before transplantation. No significant differences in outcome were observed between patients with follicular small cleaved-cell lymphoma and follicular mixed lymphoma, or between patients who received peripheral-blood stem-cell transplants and unpurged autologous bone marrow transplants. CONCLUSION: Prolonged failure-free survival is possible following high-dose therapy and autologous hematopoietic rescue for follicular low-grade lymphoma. It is unclear whether patients are cured with this therapy or if survival is prolonged.

Adult↗
PubMed1997

Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor.

PURPOSE: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration. PATIENTS AND METHODS: The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS: Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg. CONCLUSION: Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.

Adult↗
PubMed1997

Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.

PURPOSE: To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. RESULTS: The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). CONCLUSION: In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.

Adult↗