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J M Vose

Publications and source records attributed to J M Vose.

At least 19 recordsLinked to original sources

Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents.

We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.

Adolescent

Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up.

Of 364 patients with lymphoid malignancy who underwent high-dose therapy with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT), 169 patients have had progressive disease after the procedure. The median survival from the time of relapse for patients with Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma (NHL) patients (P = .0036). After failing transplantation, 56 patients were treated with further chemotherapy, 35 with involved field irradiation therapy, and 18 patients were treated with combination chemotherapy and irradiation. Seven patients received biologic therapy and seven patients underwent a second bone marrow transplant. The remainder of the patients were believed to be too ill for further therapy or chose not to receive further treatment for their recurrent lymphoid malignancy. Sixty of the 169 patients with progressive disease after the transplant are still alive; however, only 18 patients are alive off therapy without evidence of active disease after their relapse. Ten of the 18 patients are still less than 12 months past their posttransplant salvage therapy and are at high-risk for relapse. Five patients are progression free at 15 to 36 months after their posttransplant relapse. Only three patients (two NHL and one HD) treated with other modalities after autologous transplant failure are alive without evidence of disease and have been observed at least 4 years postrelapse. Although a few patients will have a durable response to subsequent therapy, the majority of patients who have progressive disease after an autologous transplant for lymphoid malignancy will succumb to recurrent disease within a short period of time.

Adult

Long-term sequelae of autologous bone marrow or peripheral stem cell transplantation for lymphoid malignancies.

The study was made to evaluate the long-term physical and psychosocial changes after high-dose therapy and autologous bone marrow or peripheral stem transplantation for recurrent lymphoid malignancies. Patients who had undergone high dose therapy and autologous bone marrow or peripheral stem cell transplantation for recurrent lymphoid malignancies at least 1 year previously were contacted by phone interview regarding their status after the transplant. The patients' comments were confirmed by checking medical records when possible. Fifty patients who had undergone transplantation at the University of Nebraska Medical Center at least 1 year before the interview were available for interview and willing to answer questions. After transplant, many patients noticed temporary changes in their appearance, which usually returned to normal within 1 year. Few patients reported remarkable cardiovascular, gastrointestinal, or pulmonary changes after transplantation. However, up to one-third of the patients reported changes in sexual function or desire. The most common infectious problem after transplant was Herpes zoster, which occurred in 25% of the patients. Overall, the patients had a positive outlook after high-dose therapy and transplantation, with most being able to return to work and enjoy a normal life style. Ninety-six percent of the patients stated that they would be willing to undergo high-dose therapy and transplantation again under the same circumstances.

Body Image

Histologic grade does not predict prognosis in optimally treated, advanced-stage nodular sclerosing Hodgkin's disease.

Forty-two patients with advanced-stage nodular sclerosing Hodgkin's disease (NSHD) were treated uniformly with combination chemotherapy and radiation therapy at the University of Nebraska Medical Center between 1982 and 1987. The cases were subclassified into low-grade (13 cases) and high-grade (29 cases) categories using the British National Lymphoma Investigation (BNLI) histologic criteria. After a median follow-up interval of 48 months, no significant differences with regard to the complete remission rate (100% versus 90%), remission durability (85% versus 96%), or predicted 4-year actuarial survival (92% versus 86%) were observed between the two groups, respectively. It was concluded that the BNLI grading scheme for NSHD does not predict the clinical outcome of patients with advanced-stage NSHD who receive optimal therapy.

Adolescent

Airway inflammation predicts diffuse alveolar hemorrhage during bone marrow transplantation in patients with Hodgkin disease.

We determined risk factors present in patients with Hodgkin disease that predicted the development of diffuse alveolar hemorrhage syndrome (DAH) during autologous bone marrow transplantation (BMT). One hundred twenty-three patients with Hodgkin disease prospectively underwent bronchoscopy with bronchoalveolar lavage (BAL) before receiving BMT. The bronchitis index (BI) of the airways and bronchial and alveolar cell counts and differentials were determined in all patients and compared with 20 normal nonsmoking volunteers. Logistic regression analysis was used to determine factors that predicted for the development of DAH. Visual evidence of bronchial injury was observed regardless of smoking history (BI = 7.8 +/- 0.5 for BMT versus 2.3 +/- 0.5 for volunteers, p = 0.001). BMT patients who developed DAH (n = 14) had significantly greater numbers of bronchial neutrophils and eosinophils compared with DAH-negative (n = 109) patients (bronchial polymorphonuclear leukocytes (PMN), 33 +/- 7% versus 14 +/- 2%, p = 0.006; bronchial eosinophils, 0.9 +/- 0.3% versus 0.4% +/- 0.07%, p = 0.02). Logistic regression analysis revealed that the presence of bronchial PMN > 20% or bronchial eosinophils > zero% were predictive of DAH (p = 0.005 and 0.05, respectively). When both predictors were positive, the rate of DAH was 10 times greater than when both predictors were negative (43% versus 4% DAH occurrence). Survival was also significantly reduced when these predictors were positive. This study demonstrates that bronchial inflammation is present with or without intraluminal inflammatory cells in the majority of patients with Hodgkin disease before BMT. The subgroup of these patients with increased bronchial inflammatory cells are at greatly increased risk for development of DAH and death.

Academic Medical Centers

Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer.

BACKGROUND: The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS: We conducted a randomized, double-blind, placebo-controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty-eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS: No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS: In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration.

Adolescent

High-dose cyclophosphamide, carmustine, and etoposide followed by autologous peripheral stem cell transplantation for patients with relapsed Hodgkin's disease.

Between February 1986 and March 1990, 56 patients with relapsed Hodgkin's disease treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) received an autologous peripheral stem cell transplantation (PSCT) rather than an autologous bone marrow transplantation (ABMT) because each patient had a marrow abnormality, either hypocellularity or tumor involvement. At least 6.5 x 10(8) [corrected] mononuclear cells/kg patient weight were collected from the peripheral blood of each patient, cyropreserved, and returned intravenously following CBV administration. Three patients had an early death 2, 22, and 25 days after PSCT. The actuarial event-free survival for these 56 patients at 3 years was 37% and was at least as good as that reported for relapsed Hodgkin's disease patients treated with CBV and ABMT. The 30 patients who had no marrow metastases at the time of PSC harvesting had an actuarial event-free survival of 47%, while those 26 patients with marrow metastases had a significantly different actuarial event-free survival of 27% (P = .02). CBV and PSCT for patients with relapsed Hodgkin's diseases who have marrow hypocellularity in traditional harvest sites or histopathologic evidence of BM metastases can result in long-term event-free survival.

Adult

The present status of therapy for patients with aggressive non-Hodgkin's lymphoma.

The aggressive non-Hodgkin's lymphomas include some of the malignancies most frequently cured with chemotherapy. However, not all patients are cured, and the best treatment approach remains uncertain. The most common aggressive non-Hodgkin's lymphomas are diffuse large-cell lymphoma and immunoblastic lymphoma. Most recent studies suggest no useful difference between these two groups. When these lymphomas are localized at presentation they are highly curable. Earlier studies showed that radiotherapy alone had a high relapse rate. Chemotherapy alone has been found to have an excellent cure rate, but when followed by radiotherapy, the amount of chemotherapy can be reduced with the same good result. A number of chemotherapy regimens have been shown to cure approximately 50% of patients with disseminated large-cell lymphoma. It appears that a number of regimens including m-BACOD, MACOP-B, LNH-84, ProMACE-CytaBOM, CAP-BOP, COP-BLAM, F-MACHOP, and perhaps full-dose CHOP achieve similar results when prognostic factors are taken into account. Currently the most important area for therapeutic research (unless new drugs are found) is in identifying those patients likely to be cured with our present treatments and those patients for whom alternative therapies such as bone marrow transplantation need to be considered as part of the primary treatment. This is true not only for large-cell lymphoma but also for the less common aggressive non-Hodgkin's lymphomas such as lymphoblastic lymphoma, small noncleaved-cell lymphoma, and peripheral T-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols

Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease.

PURPOSE: High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkin's disease. Because patients with relapsed Hodgkin's disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkin's disease. PATIENTS AND METHODS: We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS: The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION: ABMT is a more effective therapy when used early for patients with relapsed Hodgkin's disease.

Adolescent

Central nervous system involvement in patients with diffuse aggressive non-Hodgkin's lymphoma.

Central nervous system (CNS) involvement was evaluated in 277 consecutive patients with aggressive non-Hodgkin's lymphoma treated by the Nebraska Lymphoma Study Group. Three patients (1.1%) developed CNS involvement at presentation and 11 (4.0%) at relapse. The involvement was meningeal in 8 patients and documented by CSF cytology; it was parenchymal in 2 patients and proven by biopsy; and it was in the cauda equina in 1 patient at autopsy. Factors significantly associated with a greater likelihood of CNS relapse were age less than 60 years and epidural disease. Other factors, including tumor histology, extranodal disease at presentation, response to therapy, sex, and symptom type, were not significantly associated with a higher risk of CNS relapse. Survival of the patients presenting with CNS disease (6, 26, and 27+ months) was longer than patients whose CNS disease relapsed (median 2 months).

Adolescent

Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs.

The objectives of this study were to determine prognostic factors for response to treatment, freedom-from-relapse (FFR) survival, and overall survival of 737 aggressive malignant lymphoma patients treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, methotrexate with leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH-84) regimen; to construct a prognostic index with factors isolated by multivariate analyses; and to validate this prognostic index with another set of patients. Complete response (CR) was reached in 75% of LNH-84 patients, and 30% of them relapsed. With a median follow-up of 36 months, median FFR survival and median overall survival were not reached. Low serum albumin level, high tumoral mass, weight loss, bone marrow involvement, greater than or equal to 2 extranodal sites, and increased lactic dehydrogenase (LDH) level were associated with a low response rate. Advanced stage, increased LDH level, and nonlarge-cell histologic subtypes (diffuse mixed, lymphoblastic, and small non-cleaved) were statistically associated with a high relapse rate and short FFR survival. Increased LDH level, low serum albumin level, tumoral mass larger than 10 cm, greater than or equal to 2 extranodal sites, advanced stage, and age older than 65 years were statistically associated with short overall survival. Four of these parameters, namely, LDH level, stage, number of extranodal sites, and tumoral mass, were put together to construct a prognostic index. This index partitioned LNH-84 patients into three subgroups of good, intermediate, and poor prognosis (P less than .00001): CR rates of 93%, 83%, and 61%; relapse rates of 12%, 25%, and 45%; 3-year FFR survival of 87%, 73%, and 53%, and 3-year survival of 88%, 71%, and 41%, respectively. This prognostic index was applied to a test set of patients: 155 patients treated on protocols of the Nebraska Lymphoma Study Group. Using this index, these patients had 3-year FFR survival of 70%, 40%, and 22% (P = .0002) and 3-year survival of 79%, 52%, and 31% (P = .005). In patients with aggressive lymphomas, this simple prognostic index could distinguish between patients requiring intensive treatment such as autologous bone marrow transplantation in first complete remission and those who could be treated with standard regimens.

Adolescent

CHLVPP chemotherapy with involved-field irradiation for Hodgkin's disease: favorable results with acceptable toxicity.

Patients with Hodgkin's disease who were previously untreated with chemotherapy received the chlorambucil, vinblastine, procarbazine, and prednisone (CHLVPP) regimen plus limited involved-field radiation therapy for treatment of Hodgkin's disease through the Nebraska Lymphoma Study Group. One hundred patients, 87 with newly diagnosed Hodgkin's disease and 13 who relapsed after receiving previous radiation therapy, were treated with this regimen between 1982 and 1989. Complete remissions (CRs) were obtained in 88 of 100 patients (88%), and there have been a total of eight relapses. The overall 3-year failure-free survival was 76%, with good-prognosis patients (ie, Karnofsky performance status greater than or equal to 80) having a 3-year failure-free survival of 87%. Toxicity with this regimen was minimal, with neutropenic fevers reported in 13% of the patient population, moderate alopecia in 5%, and mild to moderate nausea and vomiting in 11% of the patients. As primary induction therapy for Hodgkin's disease, CHLVPP is an effective regimen with a high patient acceptance profile.

Adolescent

The use of recombinant human granulocyte-macrophage colony stimulating factor for the treatment of delayed engraftment following high dose therapy and autologous hematopoietic stem cell transplantation for lymphoid malignancies.

To test the value of recombinant human granulocyte-macrophage colony stimulating factor for the treatment of delayed engraftment following high dose therapy and autologous hematopoietic stem cell transplantation, we enrolled 12 patients with recurrent non-Hodgkin's lymphoma or Hodgkin's disease having an absolute granulocyte count less than 150 x 10(6)/l on day 30 after autologous hematopoietic stem cell infusion in an open-label, nonrandomized study. These patients were compared to 21 similar historical control patients who were not treated with colony stimulating factor. Overall, the patients treated with granulocyte-macrophage colony stimulating factor had a mean absolute granulocyte count of 704 x 10(6)/l on day 44 after stem cell infusion compared to a mean absolute granulocyte count of 408 x 10(6)/l in historical controls (p = 0.008). The number of documented bacterial and fungal infections occurring after day 30 (9 vs 0, p = 0.01) was significantly reduced in the study group. The toxicity attributed to the granulocyte-macrophage colony stimulating factor was minimal with only one patient experiencing chills. Recombinant human granulocyte-macrophage colony stimulating factor appears to be effective for the treatment of delayed engraftment following high-dose therapy and autologous hematopoietic transplantation for lymphoid malignancies, with most patients having accelerated granulocytic recovery and a reduced incidence of infections.

Adolescent

High-dose therapy and autologous peripheral stem cell transplantation for patients with bone marrow metastases and relapsed lymphoma: an alternative to bone marrow purging.

Throughout a 4-year period, we reinfused autologous peripheral stem cells rather than purged autologous bone marrow following high-dose therapy to 57 patients with relapsed lymphoma and bone marrow metastases. Approximately 7 x 10(8) circulating mononuclear cells/kg patient weight were collected for each patient with 6-19 4-h apheresis procedures while hemopoiesis was unperturbed. Following collection, the cells were cryopreserved. Administration of high-dose therapy, which included either combination chemotherapy or combination chemotherapy plus total body irradiation, was followed by i.v. administration of the thawed autologous stem cells. The rate of hemopoietic recovery varied with the specific high-dose therapy administered. Sixty-two percent of 50 evaluable patients had a clinical complete response. The actuarial event-free survival for these patients 4 years after transplantation was 30%, and the projected survival at 4 years was 51%. Patients with relapsed lymphoma and bone marrow metastases who receive high dose therapy followed by peripheral stem cell transplantation can experience long-term event-free survival. Whether similar patients would fare as well with the same high-dose therapy followed by a purged autologous bone marrow transplantation would require a randomized prospective study.

Adult

The therapy of non-Hodgkin's lymphomas. Introduction and overview.

Non-Hodgkin's lymphomas represent a diverse group of diseases that require an extensive knowledge base in order for physicians to utilize state-of-the-art therapies. This introduction outlines the current classification schemes and combination chemotherapy plans utilized for the non-Hodgkin's lymphomas.

Antineoplastic Combined Chemotherapy Protocols