Outpatient regimen rituximab plus ifosfamide, carboplatin and etoposide (R-ICE) for relapsed non-Hodgkin's lymphoma.
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Adult↗
Biomedical subjects
J Vose
Publications and source records attributed to J Vose.
The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of diffuse large cell B-cell non-Hodgkin's lymphoma: an evidence-based review.
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Antineoplastic Agents↗
Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation.
This study evaluated whether cytokine-induced blood stem cell mobilization also mobilized lymphoma cells and whether lymphoma cell mobilization affected outcome post autologous blood stem cell transplant. Blood stem cell collections from 26 non-Hodgkin's lymphoma (NHL) patients harvested during steady-state (non-mobilized) and from 35 NHL patients harvested after cytokine administration (mobilized) were studied. The harvests were cultured and molecularly evaluated for clonal markers of the primary lymphoma. All patients underwent high-dose chemotherapy and autologous transplantation. Graft products from mobilized patients were more likely to contain lymphoma than graft products from non-mobilized patients (37% vs 19%) but this difference was not significant (P = 0.16). In a multivariate analysis, lymphoma contamination was not associated with patient age, gender, tumor grade, prior radiotherapy, duration of prior chemotherapy, mononuclear cell count, or the number of aphereses performed to obtain the product. Heavily pre-treated patients were less likely to have lymphoma-contaminated harvests (P = 0.064). Lymphoma contamination was positively associated with the number of progenitor cells collected (P = 0.047). In multivariate analyses, the only significant independent predictor of lymphoma contamination was the number of mononuclear cells collected (P = 0.031). Lymphoma contamination of transplanted apheresis products had no apparent impact on event-free and overall survival.
Adult↗
Mitoxantrone and fludarabine in the treatment of patients with non-Hodgkin's lymphoma failing primary therapy with a doxorubicinor mitoxantrone-containing regimen.
Patients with recurrent lymphoma of any grade were treated with mitoxantrone (12 mg/m2 given intravenously (IV) over 15-30 minutes on day 1) followed by fludarabine at a dose of (25 mg/m 2 given IV over 30 minutes on days 1-3) every 28 days fludarabine at a dose of (25 mg/m2 given IV over 30 minutes on days 1-3) every 28 days. All patients had failed one prior chemotherapy regimen that contained either doxorubicin or mitoxantrone, total dose not exceeding 350 mg/m2 doxorubicin or 80 mg/m2 mitoxantrone. mitoxantrone. Thirty one patients (22 with intermediate- or high-grade and 9 with low-grade NHL) were enrolled. Median age was 63 years (range: 21 to 87). The objective response rate for patients with intermediate/high-grade NHL was 55% (27% with CR) and 89% (56% with CR) for patients with low-grade NHL. Median time to disease progression was 5.1 months for patients with intermediate/high-grade NHL and 10.8 months for patients with low-grade NHL. Median time to death for patients with intermediate/high-grade disease was 11.4 months. Median time to death for patients with low-grade NHL was not calculable as only one death (due to respiratory failure) occurred in this group 6.5 months after study start. The regimen was well tolerated. Grade 3/4 neutropenia was reported in 80% (24 of 30) of patients and Grade 3/4 thrombocytopenia in 19% (6 of 31) of patients. Nine hospitalizations for adverse events (primarily fever and neutropenia) occurred among eight patients, all with intermediate/high-grade NHL, during a total of 118 cycles of therapy. Further studies of this combination regimen in patients with intermediate/high-grade NHL and studies combined with monoclonal antibodies in low-grade NHL are warranted.
Adult↗
A phase II multicenter study of CAMPATH-1H antibody in previously treated patients with nonbulky non-Hodgkin's lymphoma.
CAMPATH-1H is a humanized antilymphocyte monoclonal antibody (mAb) directed against the CD52 antigen expressed on normal and malignant lymphocytes. We report the results of a multicenter phase II trial using intravenous CAMPATH-1H in previously treated patients with nonbulky non-Hodgkin's lymphoma (NHL) or minimal residual NHL. Sixteen previously treated patients with nonbulky NHL and two patients with minimal residual NHL, were treated with CAMPATH-1H. Changes in peripheral blood lymphocyte subsets were analyzed by multiparameter flow cytometric techniques in eleven patients. The 18 patients enrolled in the studies received CAMPATH-1H for a median duration of 6 weeks (range, 3 to 14 weeks), and a median cumulative dose of 470 mg (range, 180 to 1185 mg). Two of the sixteen patients with nonbulky NHL achieved a complete response (CR) and one patient achieved a partial response (PR). One of the two patients with minimal residual NHL achieved a molecular CR. Infusional complications were seen with the majority of patients but were more common with initial infusions. Significant hematologic toxicity was also observed with grade (3/4) thrombocytopenia (n=10), grade (3/4) neutropenia (n=4) and grade 3 anemia (n=3). Due to excessive infectious complications observed with the patients enrolled, the trials were terminated early. Anti-tumor activity was demonstrated in a small subset of previously treated low-grade lymphoma patients with nonbulky or minimal residual disease. Future studies evaluating the effect of different drug schedules, modes of mAb administration, and concurrent use of prophylactic antibiotics/antiviral/antifungal agents to optimize anti-tumor activity and limit infectious toxicities are planned.
Adult↗
Detection of gamma-butyrolactone (GBL) as a natural component in wine.
The compound gamma-butyrolactone (GBL) was found in extracts from samples of unadulterated wines. This finding indicates that GBL is a naturally occurring component in some wines and may be present in similar products. The concentration detected was approximately 5 microg/mL and was easily observed using a simple extraction technique followed by GC/MS analysis. These results illustrate the need to carefully examine an allegedly adulterated sample's matrix before determining a sample was laced with GBL.
4-Butyrolactone↗
A phase I trial of recombinant human thrombopoietin in patients with delayed platelet recovery after hematopoietic stem cell transplantation.
Delayed platelet recovery is a significant complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). A multicenter, phase I dose-escalation study of recombinant human thrombopoietin (rhTPO) was conducted to assess its safety and to obtain preliminary data on its efficacy in patients with persistent severe thrombocytopenia (<20,000/microL) >35 days after HSCT. Thirty-eight patients, 37 of whom were evaluable, were enrolled in the study from April 1996 through January 1997. rhTPO was administered at doses of 0.6, 1.2, and 2.4 microg/kg as a single dose (group A) or in multiple doses every 3 days for a total of 5 doses (group B). No significant adverse effects were observed. Ten patients had recovery of platelet counts during the 28-day study period; 3 of these 10 had an increase in marrow megakaryocyte content 7 days after completing treatment with rhTPO. When all baseline marrows were compared with samples after rhTPO treatment, there was no difference in marrow megakaryocyte content (P = 0.49). This study design could not answer the question of whether the recoveries of platelet counts observed in some patients were spontaneous or influenced by rhTPO treatment; nonetheless, the authors found no correlation between the dose of rhTPO and the recovery of platelet counts. Increases in serum TPO levels were dose-dependent and remained significantly elevated for up to 72 hours after treatment. To evaluate response, further studies of treatment strategies with rhTPO in patients with delayed platelet recovery are required.
Adolescent↗
Costs of care associated with high-dose therapy and autologous transplantation for non-Hodgkin's lymphoma: results from the University of Nebraska Medical Center 1989 to 1995.
The purpose of this paper was to (1) comprehensively analyze transplant-related costs for predicted temporal cost shifting and (2) to evaluate whether previous findings of decreasing costs of care persisted using a cost analysis of 353 NHL patients who received autologous stem cell transplantation (SCT) at the University of Nebraska Medical Center. All transplant-related costs between the patient's initial consult and program dismissal were obtained and inflated to constant 1995 dollars. Homogeneous resources were categorized into six cost-drivers and subdivided into outpatient, transplant, and additional inpatient time periods in order to evaluate resource utilization and cost shifting patterns. Between 1989 and 1991 both the average length of stay and comprehensive costs decreased 4.9 days and 14%, respectively. By 1995 additional decreases of 25.7 days and 51% led to an overall 7 year cost decline of 65%. Percent contributions of the six cost-drivers remained similar demonstrating uniformed suppression in transplant-related resource consumption. In contrast, the timing of resource utilization changed dramatically, with transplant hospitalization costs accounting for 83% of the overall costs in 1989, 71% by 1992, and only 45% in 1995, while total outpatient's contribution was 14%, 26% and 49%. Before 1991 ebbing costs were likely related to the development of new technologies such as hematopoietic growth factors and peripheral SCT, while the three-fold larger improvement in costs reported by 1995 are presumably associated with learning curve effects such as organizational changes, increased use of coordinated outpatient facilities, and the more cost-effective use of laboratory tests and pharmaceuticals.
Adolescent↗
Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group.
Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.
Clinical Trials as Topic↗
A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation.
Many of the complications of high-dose therapy with hematopoietic stem cells are caused by or lead to the multiple-organ dysfunction syndrome (MODS). In hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII) deficiency is independently associated with MODS to the exclusion of transplant type, preparative regimen, and bacteremia. In experimental settings, replacement of ATIII can ameliorate the severity of MODS that develops in response to a variety of pathologic stimuli, suggesting that ATIII supplementation might improve the clinical course of MODS in patients undergoing HSCT. We performed a study to determine if ATIII can improve the morbidity of MODS in HSCT. Forty-nine patients undergoing HSCT, who developed pulmonary dysfunction (oxygen saturation of <90%), central nervous system dysfunction (drop of >4 points in the mini-mental status exam), or hepatic dysfunction (bilirubin >34 micromol/L [2.0 mg%], weight gain of >5% over baseline, and abdominal pain, possibly of hepatic origin) with a concomitant ATIII activity of <84% were double-blind randomized to receive ATIII concentrate, 70 units/kg within 24 hours of recognition of initial organ dysfunction followed by 50 units/kg 8, 16, 48, and 72 hours later, or albumin placebo. The group randomized to ATIII had a lower severity-of-illness score (15.7 +/- 19.2 vs. 28.6 +/- 25.2, p = 0.03), shorter duration of hospitalization (14.9 +/- 16.7 vs. 25.7 /- 17.9 days, p = 0.03), and lower hospital charges ($138,700 +/- $23,500 vs. $206,400 +/- $34,000). ATIII concentrate was associated with improved morbidity of MODS in patients undergoing HSCT when given early in the evolution of the syndrome.
Adult↗
The detection of minimal lymphoma by molecular and combined culture-molecular methods.
Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem cell (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14:18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14;18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of tumour detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.
Base Sequence↗
2-Chlorodeoxyadenosine as initial therapy for advanced low grade lymphomas.
In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA was initiated in patients with previously untreated advanced low grade lymphoma. Fourteen previously untreated patients with stage III and IV low grade lymphoma were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one complete response and nine partial responses for an overall response rate of 75%. Until now there have only been three responding patients who have had progressive disease, with a median follow-up time of 18 months. The major toxicity was bone marrow suppression and nine patients stopped therapy prior to a planned six cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50 cycles of therapy were associated with neutropenic febrile episodes and there was one septic death secondary to Listeriosis. It seems from this small group of patients that 2-CdA is an active agent in previously untreated low grade lymphoma. Myelosuppression is cumulative and limits the number of cycles of therapy which can be given. Future exploration of different doses or schedules of this active agent is warranted.
Adult↗
Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.
PURPOSE: A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS: The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION: High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.
Adolescent↗
Myelodysplastic syndrome after autologous transplant for lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗
Clinical outcome of peripheral blood stem cell support.
Two clinical results of peripheral blood stem cell support are commonly considered: (1) the effect on hematopoietic recovery and (2) the effect on the underlying malignancy. The dynamics of hematopoietic recovery after autologous bone marrow transplantation and after autologous peripheral blood stem cell transplantation in a clinical setting are similar if no exogenous cytokines are administered and the peripheral stem cells are collected while their numbers are not deliberately increased (mobilised). If mobilized peripheral stem cells are transplanted, hematopoietic recovery is accelerated. In some circumstances, patients who receive peripheral stem cell transplantation may experience an improved progression-free survival after high-dose therapy when compared with similar patients who receive autologous bone marrow transplantation. Explanations for such a survival advantage might include (1) a lower likelihood of occult tumor cells capable of restoring disease in peripheral stem cell autograft products than in bone marrow harvests, (2) a greater number of cytotoxic effector cells capable of destroying occult tumor cells in the peripheral stem cell collections than in bone marrow harvests, and (3) a different and advantageous pattern of immunologic recovery following autologous peripheral stem cell transplant compared to autologous bone marrow transplant.
Hematopoietic Stem Cell Transplantation↗
Hospitalized teens. Ambulatory care utilization patterns.
Twelve- to eighteen-year-olds enrolled in a federally qualified HMO in Central Massachusetts who had an admission to a hospital with a diagnosis of trauma or mental health problems were identified. Routine and episodic health care utilization for a 24-month period of each study case was determined and compared with the same for a comparison group matched for age, sex and length of enrollment. Although information on health habits and lifestyle was often missing from the charts, it was determined that the study cases were less likely to be in school and living with their parents and used episodic care more frequently, especially in the 6 months prior to admission. Both hospitalized and non-hospitalized youth had a higher average number of visits to office-based providers than their national counterparts. The study suggests that (1) greater awareness of morbidity and health care utilization patterns and risk behaviors may enhance prevention efforts; (2) use of instruments to capture more information on health habits and lifestyle may facilitate preventive interventions; (3) collaborations among pediatric primary care providers, the Information Services (IS) and Quality Management (QM) departments may facilitate this type of research in a managed care setting.
Adolescent↗
Laparoscopic cholecystectomy. A clinical and financial analysis of 280 operations.
Two hundred eighty patients underwent laparoscopic cholecystectomy (LC) and were compared with 304 patients who underwent traditional "open" cholecystectomy (OC). Laparoscopic cholecystectomy was performed electively in 72.5% of cases and urgently in 27.5% of cases. Conversion from LC to OC was required in 14 patients (5%), six of whom required common bile duct exploration. Common bile duct stones were managed with video-laparoscopic techniques in 11 patients, with percutaneous transhepatic laser lithotripsy in three patients, and with laparotomy in six patients. Hospital stay was significantly shorter and complications were significantly fewer for LC compared with OC. Hospital expenses for LC were significantly higher than for OC because of longer duration of operation and higher operating room expenses. Patients who underwent elective LC returned to work an average of 31 days earlier than patients who underwent OC (10 days vs 41 days). These data indicate that LC can be performed safely although at a higher cost than OC, and that patients as well as employers benefit from a short length of hospital stay.
Adult↗