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Biomedical subjects

Peter McLaughlin

Publications and source records attributed to Peter McLaughlin.

At least 19 recordsLinked to original sources
PubMed2007

Experience with heat shock protein-peptide complex 96 vaccine therapy in patients with indolent non-Hodgkin lymphoma.

BACKGROUND: The objective of this phase II trial was to investigate the safety and efficacy of autologous heat shock protein-peptide complex 96 (HSPPC-96) vaccines prepared from tumor specimens of patients with newly diagnosed or previously treated indolent non-Hodgkin lymphoma (NHL). METHODS: The study was for patients with indolent B-cell NHL with measurable lesions. HSPPC-96 vaccines were prepared from patients' resected tumor specimens and administered as a 25-microg intradermal injection in the absence of disease progression every week for 4 weeks and then every 2 weeks until the vaccine supply was exhausted. RESULTS: Twenty patients were enrolled in this trial. The median patient age was 59 years. Ten patients had been treated previously (median, 2 regimens; range, 1 to 7). Eighteen (90%) patients had stage III or IV disease. Autologous vaccines were successfully prepared for 17 (85%) patients and all received at least 1 dose. The treatment was very well tolerated. One patient experienced a response with biopsy-proven clearance of the lymphoma cells in 2 of the skin nodules at 3.0 months that lasted for 7.0 months. Eight patients had stable disease for 6.0 to 19.8 months. The median failure-free survival duration in patients who received vaccine therapy was 5.2 months. CONCLUSIONS: HSPPC-96 can be prepared from tumor specimens for the majority of lymphoma patients, but it had limited efficacy in inducing responses in patients with active diseases. Further studies of HSPPCs, therefore, should be considered in adjuvant settings or in combination with other immunomodulatory agents to assess survival benefit.

Aged↗
PubMed2006

Dose-related safety and immunogenicity of baculovirus-expressed trivalent influenza vaccine: a double-blind, controlled trial in adult patients with non-Hodgkin B cell lymphoma.

In 27 patients randomized to receive commercial trivalent influenza vaccine (TIV) containing 15 microg of the hemagglutinin (HA) of influenza A (H3N2 and H1N1) and B virus or a recombinant vaccine (rHAO) containing 15, 45, or 135 microg of each HA, reactogenicity was minor. Among patients with similar prevaccination titers, 40% given 45 microg and 60% given 135 microg of rHAO developed an increase in influenza A/H3 neutralizing antibody levels; there were no increases in 4 given TIV. For each vaccine, the highest frequencies of increases in neutralizing antibody levels and the highest mean titers occurred in those given the 135- microg vaccine.

Antibodies, Viral↗
PubMed2006

Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center.

PURPOSE: Advanced-stage follicular lymphoma is considered incurable. The pace of improvements in treatment has been slow. This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002. METHODS: Five consecutive studies (two were randomized trials) involving 580 patients were analyzed for overall survival (OS), failure-free survival (FFS), and survival after first relapse. A proportional hazards analysis, and subset analyses using the follicular lymphoma international prognostic index (FLIPI) score were performed. Treatment regimens included: cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin (CHOP-Bleo); CHOP-Bleo followed by interferon alfa (IFN-alpha); a rotation of three regimens (alternating triple therapy), followed by IFN-alpha; fludarabine, mitoxantrone, dexamethasone (FND) followed by IFN-alpha; and FND plus delayed versus concurrent rituximab followed by IFN-alpha. RESULTS: Improvements in 5-year OS (from 64% to 95%) and FFS (from 29% to 60%) indicate steady progress, perhaps partly due to more effective salvage therapies, but the FFS data also indicate improved front-line therapies; these observations held true after controlling for differences in prognostic factors among the cohorts. The FLIPI model adds rigor to and facilitates comparisons among the different cohorts. An unexpected finding in this study was a trend toward an apparent FFS plateau. CONCLUSION: Evolving therapy, including the incorporation of biologic agents, has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma. The apparent plateau in the FFS curve, starting approximately 8 to 10 years from the beginning of treatment, raises the issue of the potential curability of these patients.

Adult↗
PubMed2006

The role of cardiac catheterization in adult congenital heart disease.

The role of heart catheterization continues to evolve as the sophistication of cardiac MRI and CT improves and the breadth of interventional catheter techniques widens. This analysis is approached from four perspectives: (1) planning of the procedure, including information required, potential pitfalls, and equipment; (2) performance of the procedure, including sample run, coronary arteriography, chamber angiography, and angiography of selected lesions; (3) current role of heart catheterization, considering the impact of echo, MRI, and CT on indications for catheterization procedures and current interventional procedures; and (4) new and emerging interventions and speculation as to the future role of diagnostic heart catheterization in patients who have adult congenital heart disease.

Adult↗
PubMed2006

Pegfilgrastim administered in a single fixed dose is effective in inducing neutrophil count recovery after paclitaxel and topotecan chemotherapy in patients with relapsed aggressive non-Hodgkin's lymphoma.

Pegfilgrastim is a pegylated form of a granulocyte colony-stimulating factor with a long half-life allowing for a single administration per chemotherapy cycle. The efficacy of a single dose of pegfilgrastim in supporting severely myelosuppressive regimens in previously treated cancer patients is unknown. Patients included in the present study had recurrent or refractory aggressive non-Hodgkin's lymphoma (NHL), had received two to three prior treatment regimens, and had good performance status and marrow reserve. Patients received intravenous paclitaxel 200 mg/m(2) on day 1 and topotecan 1 mg/m(2) daily for 5 days, repeated every 21 days for at least two cycles. On day 6, patients were given a single fixed dose of pegfilgrastim (6 mg) subcutaneously. Twenty patients were evaluable for analysis. After the first course of therapy, grade 4 neutropenia developed in all 20 patients. The median time to the neutrophil nadir was 9 days. The mean +/- SD duration of grade 4 neutropenia was 3.8 +/- 1.7 days. Nineteen (95%) patients received cycle 2 on time, on day 22. Five patients developed neutropenic fever (25%), which was associated with infection in one patient. In these previously treated patients with NHL, a single dose of pegfilgrastim was effective in promoting neutrophil count recovery after paclitaxel and topotecan, and allowed patients to receive the next planned dose on time.

Adult↗
PubMed2006

Phase 2 study of fludarabine and paclitaxel in patients with recurrent low-grade non-Hodgkin's lymphoma.

Although numerous options are available for patients with recurrent low-grade non-Hodgkin's lymphoma (NHL), responses are rarely durable. We previously conducted a phase I trial of fludarabine and paclitaxel in the treatment of recurrent low-grade lymphoma. The present phase II study was performed to determine the activity of fludarabine and paclitaxel in patients with recurrent low-grade NHL. Patients with histologically confirmed recurrent low-grade NHL were treated with fludarabine 20 mg/m2/day intravenously (i.v.) on days 1-5 plus paclitaxel 50 mg/m2 given by i.v. continuous infusion over 72 h starting on day 1. Treatment was repeated at 4-week intervals for a maximum of six courses. Twenty-eight evaluable patients were entered into this phase II trial. The median age was 53 years and the median performance status (Zubrod) was 1. Twenty-two (78%) patients had grade 1 or 2 follicular lymphoma, and six patients (21%) had small lymphocytic lymphoma. The median number of prior chemotherapy regimens was 1 (range, 1-3). Objective responses occurred in 16 patients (57%); nine patients (32%) achieved a complete remission with a median duration of 32 months (range 4-84+ months), and seven patients (25%) had a partial remission. Grade 3 and 4 toxicities included neutropenia (72%), neutropenic fever (34%), infection (13%), mucositis (7%), and neuropathy (3%). The combination of fludarabine and paclitaxel has clinical activity in patients with recurrent low-grade NHL.

Adult↗
PubMed2005

High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine.

PURPOSE: To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL). PATIENTS AND METHODS: This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles. RESULTS: Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred. CONCLUSION: Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.

Administration, Oral↗
PubMed2005

A prospective randomized study to compare the molecular response rates between central lymphatic irradiation and intensive alternating triple chemotherapy in the treatment of stage I-III follicular lymphoma.

PURPOSE: This study was undertaken to compare the molecular response (MR) rates of 2 regimens, central lymphatic irradiation (CLI) and alternating triple therapy (ATT), in the treatment of Stage I-III follicular lymphoma. MR was defined as disappearance of t(14;18) (q32;q21) amplified by polymerase chain reaction (PCR). PATIENTS AND METHODS: Sixty-five patients with Stage I to III follicular lymphoma were randomized. CLI consisted of the mantle, abdomen, and pelvic radiation fields. ATT alternated among CHOD-Bleo, ESHAP, and NOPP for 12 courses. Bone marrow (BM) and peripheral blood (PB) samples were obtained before treatment for PCR analysis. PCR-positive patients were followed by PCR analysis. The random-effects logistic model was fitted to the data from the posttreatment PCRs. The factors included in the model were treatment arm, type of PCR (BM vs. PB), and time to PCR sample procurement from the date of registration. RESULTS: At a median follow-up of 71 months, the 5-year relapse-free survival (RFS) rates were 45% and 54% for CLI and ATT, respectively (p = 0.42). The probability of attaining an MR increased with time after registration (p = 0.007), was lower for BM compared with PB (p = 0.012), and was higher for ATT than for CLI (p = 0.020). CONCLUSION: ATT regimen achieved a higher MR than CLI, although both arms had similar 5-year RFS.

Adult↗
PubMed2005

Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma.

BACKGROUND: Oxaliplatin is a platinum derivative with a broad range of anticancer activity. The objective of the current Phase II trial was to investigate the activity of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma (NHL). METHODS: Patients with recurrent and refractory NHL who received a maximum of 3 previous chemotherapy regimens were considered eligible if they had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Oxaliplatin was administered in an outpatient setting at a dose of 130 mg/m(2) by 2-hour intravenous infusion every 21 days for < or = 6 cycles in the absence of disease progression. RESULTS: Thirty-one patients (23 with aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable for toxicity, response, and survival. The median patient age was 62 years, and 20% of the patients previously received platinum-containing therapy. Eighty-three percent of the patients were refractory to their last treatment regimens. Grade 3 and 4 toxic effects (according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence interval, 13-47%) of the patients. Responses were observed in platinum-naive patients as well as in those previously treated with platinum. The overall median failure-free survival duration was 3.0 months (range, 0.1-18.1 months). CONCLUSIONS: Oxaliplatin had favorable single-agent activity in previously treated patients with refractory lymphoma. The favorable safety profile and the ease of its administration in outpatient settings warrant investigating it in combination with other active drugs for the treatment of recurrent and refractory NHL.

Adult↗
PubMed2005

Immunosuppression and infectious complications in patients with stage IV indolent lymphoma treated with a fludarabine, mitoxantrone, and dexamethasone regimen.

BACKGROUND: Myelosuppression and immunosuppression occur with purine analogs. The objective of the current study was to investigate the effects of combined fludarabine, mitoxantrone, and dexamethasone (FND) followed by interferon/dexamethasone on myelosuppression (absolute neutrophil counts), immunosuppression (CD4 and CD8 counts), and infectious complications in patients with previously untreated, Stage IV indolent lymphoma. METHODS: Seventy-three patients were treated. All patients received Pneumocystis carinii pneumonia (PCP) prophylaxis. CD4 and CD8 counts, serum immunoglobulin (Ig) levels, and neutrophil counts were correlated with infectious complications. RESULTS: The median follow-up was 6.1 years. Sixty of 73 patients had CD4, CD8, or Ig measurements. The median baseline CD4 count was 764/microL. This CD4 level decreased to 238/microL at 1 year and to 264/microL at 2 years; and it rose to 431/microL by 3 years and to 650/microL at 4 years. CD8 counts did not change significantly. The median baseline serum IgG level was 989 mg/d, decreased to 536 mg/dL at 1 year and to 693 mg/dL at 2 years, and it rose to 949 mg/dL at 3 years and to 1080 mg/dL at 4 years. Fourteen patients (19%) developed Grade 3-4 infections, the majority during FND therapy with neutropenia and/or accompanied by CD4 counts < 200/microL. CD4, CD8, and neutrophil counts did not differ between patients who developed Grade 3-4 infections, Grade 1-2 infections, or no infections. CONCLUSIONS: Most infections with FND occurred during FND, in the setting of neutropenia, often with concurrent low CD4 counts. The overall safety profile for FND was good. However, patients should be monitored for opportunistic infections, and prophylactic antibiotics are recommended, particularly against PCP.

Adult↗
PubMed2005

Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin's lymphomas.

PURPOSE: We investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m(2) and 7 days after chemotherapy at 1,000 mg/m(2)), together with granulocyte colony-stimulating factor 10 mug/kg and granulocyte-macrophage colony-stimulating factor 250 microg/m(2) administered subcutaneously daily. HD-R of 1,000 mg/m(2) was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab. RESULTS: With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to >/= 500 cells/microL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab. CONCLUSION: The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Adult↗
PubMed2005

Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha.

Treatment-related myelodysplasia (t-MDS) occurs less frequently with the nucleoside analogs than with DNA-damaging agents such as alkylators or topoisomerase II inhibitors. In a chemoimmunotherapy trial conducted between 1997 and 2003 in patients with stage IV indolent lymphoma, 202 patients were treated and 8 have developed MDS between 1 and 5 years after therapy, including 4 who received only fludarabine, mitoxantrone, and dexamethasone (FND) for 6 to 8 courses, with or without rituximab, followed by interferon alpha (IFN-alpha). Complex cytogenetic abnormalities were present in all patients. Abnormalities of chromosome 7 were present in 6 of the 8 patients, 3 of whom received only FND +/- rituximab and IFN-alpha. The abnormalities of chromosome 7 were monosomy 7 in 4 patients (1 of which had add 7p in the remaining chromosome); 1 del 7q; and 1 der 7. MDS with features classically associated with DNA-damaging agents can occur following therapy with FND, with or without rituximab, and IFN-alpha.

Adult↗
PubMed2005

Improvements in cardiac form and function after transcatheter closure of secundum atrial septal defects.

OBJECTIVES: We set out to study the effect of transcatheter closure of atrial septal defect (ASD) on right ventricular (RV) and left ventricular (LV) function assessed by myocardial performance index (MPI), as well as left atrial (LA) volumes. BACKGROUND: The hemodynamic response to the closure of ASD is well-documented in surgically treated patients. However, few studies have documented echocardiographic evaluation of ventricular function in patients undergoing transcatheter closure of ASDs. METHODS: Pre- and post-ASD device closure echocardiograms of 25 consecutive patients were retrospectively reviewed. Measurements of RV and LV MPI and LA volumes were made. RESULTS: Twenty-five patients with an average age of 45.5 +/- 16.3 years underwent transcatheter closure of ASD. There was statistically significant improvement in RV MPI (0.35 to 0.28, p = 0.004), LV MPI (0.37 to 0.31, p = 0.04), and LA volume index (25.7 to 21.8 ml/m(2), p < 0.001) after closure of ASD. CONCLUSIONS: Device closure of ASDs leads to improvement of both RV and LV function as well as reduction in LA volume. These hemodynamic improvements provide insights into the symptomatic benefits gained in closure of ASDs using the transcatheter approach.

Adult↗
PubMed2004

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.

Adult↗
PubMed2004

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.

Adult↗
PubMed2004

Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation.

PURPOSE: Allogeneic transplantation for patients with lymphoma who experience a recurrence after an autologous transplantation has been considered a hazardous therapeutic choice. We investigated the safety and efficacy of nonmyeloablative stem-cell transplantation in these patients. PATIENTS AND METHODS: Patients were required to have chemosensitive or stable disease. Twenty consecutive patients were treated in two sequential trials. Fifteen patients underwent a preparative regimen of fludarabine (30 mg/m(2) daily for 3 days), intravenous cyclophosphamide (750 mg/m(2) daily for 3 days), and rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m(2) continuous infusion daily for 4 days), fludarabine (30 mg/m(2) daily for 2 days), and cytarabine (1,000 mg/m(2) daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. RESULTS: All patients experienced engraftment of donor cells. One patient (5%) experienced grade 2 acute graft-versus-host disease, and no patients experienced a higher grade. One patient experienced disease progression at 115 days post-transplantation and responded to donor lymphocyte infusion. The remaining patients remained disease-free. One patient died at 10.5 months from a fungal infection. With a median follow-up time of 25 months, the estimated 3-year current progression-free survival rate was 95%. CONCLUSION: These data suggest that nonmyeloablative allogeneic stem-cell transplantation is an effective option in lymphoma patients with chemosensitive or stable disease who experience disease recurrence following autologous transplantation.

Adult↗