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As appropriations earmarks return to Congress, every legislator faces a decision: pursue or refuse congressionally mandated federal spending projects. This decision is likely influenced by public messaging concerns. We theorize that both credit claiming for federal projects and position taking against spending projects (“pork busting”) can benefit legislators as they look to improve future electoral returns. We field a nationally representative survey experiment to estimate the effect of credit‐claiming and pork‐busting messages on the perceived effectiveness, fiscal responsibility, and overall approval of an unnamed member of Congress. We find that respondents are likely to penalize the representative's approval assessment when presented with an out‐party message strategy. Conversely, respondents are likely to increase the representative's personal trait assessments when presented with an in‐party message strategy. We expand on these results in an additional analysis and find that these trends persist when controlling for other partisan and demographic factors. We discuss our results in light of traditional expectations, potential mechanisms, and future directions for related research.

ABSTRACTThe US Congress is unrepresentative of the people it serves, and reforming campaign finance law may be a path toward a more representative institution. We examine public opinion toward allowing candidates to use campaign funds for child care, theorizing gender conditions support due to the unequal burden child care places on women. Using an experiment, we find people are more supportive of candidates using campaign funds for child care when the hypothetical candidates are women. Women respondents are especially likely to vary their support for the policy based on candidate gender. This project is the first to explore public support for allowing candidates to use campaign funds for personal expenses, contributing to our understanding of support for reform that could transform the types of candidates willing to run.

We present the frequency-dependent geminal-screened electron–hole interaction kernel (FD-GSIK) method for describing electron–hole correlation in electronically excited many-electron systems. The FD-GSIK is a parameter-free, first-principles method derived from excited-state wave function that was both frequency-dependent and r12-explicitly correlated. The FD-GSIK avoids using unoccupied orbitals for kernel construction by performing an infinite-order summation of particle-hole excitation and representing it as a compact real-space operator. It bypasses the computationally demanding steps of evaluation, storage, and transformation of atomic-orbital integrals by directly evaluating molecular orbital integrals in real space using the stratified Monte Carlo method. We demonstrate and discuss the advantages of this method by presenting excitation and electron–hole binding energies of large nanoparticles including Pb140S140, Pb140Se140, Cd144Se144, and Cd72S72.

Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P= .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P= .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.

Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.

The overarching goal of this work is to investigate the size-dependent characteristics of the ionization potential of PbS and CdS quantum dots. The ionization potentials of quantum dots provide critical information about the energies of occupied states, which can then be used to quantify the electron-removal characteristics of quantum dots. The energy of the highest-occupied molecular orbital is used to understand electron-transfer processes when invesigating the energy-level alignment between quantum dots and electron-accepting ligands. Ionization potential is also important for investigating and interpreting electron-detachment processes induced by light (photoelectron spectra), external voltage (chemiresistance), and collision with other electrons (impact ionization). Accurate first-principles calculations of ionization potential continue to be challenging because of the computational cost associated with the construction of the frequency-dependent self-energy operator and the numerical solution of the associated Dyson equation. The computational cost becomes prohibitive as the system size increases because of the large number of 2particle-1hole (2p1h) and 1particle-2hole (1p2h) terms needed for the calculation. In this work, we present the Stratified Stochastic Enumeration of Molecular Orbitals (SSE-MO) method for efficient construction of the self-energy operator. The SSE-MO method is a real-space method and the central strategy of this method is to use stochastically enumerated sampling of molecular orbitals and molecular-orbital indices for the construction of the 2p1hand 1p2hterms. This is achieved by first constructing a composite MO-index Cartesian coordinate space followed by transformation of the frequency-dependent self-energy operator to this composite space. The evaluation of both the real and imaginary components of the self-energy operator is performed using a stratified Monte Carlo technique. The SSE-MO method was used to calculate the ionization potentials and the frequency-dependent spectral functions for a series of PbS and CdS quantum dots by solving the Dyson equation using both single-shot and iterative procedures. The ionization potentials for both PbS and CdS quantum dots were found to decrease with increasing dot size. Analysis of the frequency-dependent spectral functions revealed that for PbS quantum dots the intermediate dot size exhibited a longer relative lifetime whereas in CdS the smallest dot size had the longest relative lifetime. The results from these calculations demonstrate the efficacy of the SSE-MO method for calculating accurate ionization potentials and spectral functions of chemical systems.

CB1 antagonists, including rimonabant (SR 141716A), hold considerable therapeutic potential in the reduction of appetite and lipogenesis and in improving the metabolic profile of obese individuals and those with diabetes. However, rimonabant has not been approved in the USA because of its numerous side-effects, including depression and anxiety. Because of this, it is expected that fewer attempts will be made to introduce CB1 antagonists into the market. However, a ‘second generation’ of compounds has produced promising results in animal models in terms of these side-effects, and may pave the way toward new development and clinical testing of compounds that lack the side-effects of rimonabant. This new generation includes neutral CB1 antagonists, which likely have less intrinsic activity than clinically tested drugs, and peripherally restricted compounds. The current paper reviews the behavioral profile of rimonabant and related compounds, including a similarity in hypophagic effects with putative neutral antagonists and peripherally restricted antagonists. Emerging evidence of a lack of effects in models of nausea, anxiety, and depression is discussed. It is concluded that, with increasing emphasis on modeling the more troublesome side-effects of CB1 antagonists, safe, efficacious therapeutic targets may emerge. Further rigorous preclinical testing should be carried out.

In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m2 weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHLwas 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial. This trial has been completed and is registered with www.clinicaltrials.gov as NCT00504504.

Nonmyeloablative stem cell transplantation in patients with follicular lymphoma has been designed to exploit the graft-versus-lymphoma immunity. The long-term effectiveness and toxicity of this strategy, however, is unknown. In this prospective study, we analyzed our 8-year experience. Patients received a conditioning regimen of fludarabine (30 mg/m2daily for 3 days), cyclophosphamide (750 mg/m2daily for 3 days), and rituximab (375 mg/m2for 1 day plus 1000 mg/m2for 3 days). They were then given an infusion of human leukocyte antigen-matched hematopoietic cells from related (n = 45) or unrelated donors (n = 2). Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Forty-seven patients were included. All patients experienced complete remission, with only 2 relapses. With a median follow-up time of 60 months (range, 19-94), the estimated survival and progression-free survival rates were 85% and 83%, respectively. All 18 patients who were tested and had evidence of JH/bcl-2fusion transcripts in the bone marrow at study entry experienced continuous molecular remission. The incidence of grade 2-IV acute GVHD was 11%. Only 5 patients were still undergoing immunosuppressive therapy at the time of last follow-up. We believe that the described results are a step forward toward developing a curative strategy for recurrent follicular lymphoma.

Nonmyeloablative stem cell transplantation in patients with follicular lymphoma has been designed to exploit the graft-versus-lymphoma immunity. The long-term effectiveness and toxicity of this strategy, however, is unknown. In this prospective study, we analyzed our 8-year experience. Patients received a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and rituximab (375 mg/m2 for 1 day plus 1000 mg/m2 for 3 days). They were then given an infusion of human leukocyte antigen-matched hematopoietic cells from related (n = 45) or unrelated donors (n = 2). Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Forty-seven patients were included. All patients experienced complete remission, with only 2 relapses. With a median follow-up time of 60 months (range, 19-94), the estimated survival and progression-free survival rates were 85% and 83%, respectively. All 18 patients who were tested and had evidence of JH/bcl-2 fusion transcripts in the bone marrow at study entry experienced continuous molecular remission. The incidence of grade 2-IV acute GVHD was 11%. Only 5 patients were still undergoing immunosuppressive therapy at the time of last follow-up. We believe that the described results are a step forward toward developing a curative strategy for recurrent follicular lymphoma.

OBJECTIVE To determine the stage at initial examination and the prevalence of systemic involvement in patients with orbital and ocular adnexal lymphoma. METHODS The medical records of all patients with orbital and ocular adnexal lymphoma treated in a recent 7-year period were reviewed for stage at initial examination, highest stage during the follow-up period, and recurrence-free survival. RESULTS Forty-three patients were included. Nineteen patients had mucosa-associated lymphoid tissue, 9 had follicular, 9 had diffuse large-cell, 3 had mantle cell, 2 had small lymphocytic, and 1 had large T-cell lymphoma. The staging workup included chest radiography; orbital computed tomography or magnetic resonance imaging; computed tomography of the chest, abdomen, and pelvis; and bone marrow biopsy. Thirty-six patients had total body positron emission tomography, 7 had gallium scans, and 16 had gastrointestinal endoscopy. Lymphoma stage at diagnosis was IE in 18 patients, II in 6, and IV in 19. Six of 19 patients with mucosa-associated lymphoid tissue, 7 of 9 patients with follicular, 6 of 9 patients with diffuse large-cell, and 3 of 3 patients with mantle cell lymphoma had non–stage IE disease at initial examination. The 5-year recurrence-free survival was 64.6% for the entire cohort. CONCLUSIONS Extraorbital involvement is present at diagnosis in more than half of patients with orbital and ocular adnexal lymphoma and warrants extensive systemic workup at diagnosis, continued surveillance, and consideration of systemic therapy.Arch Ophthalmol. 2007;125(12):1663-1667--

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).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/m2 by 2‐hour intravenous infusion every 21 days for ≤ 6 cycles in the absence of disease progression.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).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. Cancer 2005. © 2005 American Cancer Society.

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.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.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/μL: This CD4 level decreased to 238/μL at 1 year and to 264/μL at 2 years; and it rose to 431/μL by 3 years and to 650/μL 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/μL. CD4, CD8, and neutrophil counts did not differ between patients who developed Grade 3–4 infections, Grade 1–2 infections, or no infections.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. Cancer 2005. © 2005 American Cancer Society.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs ≤ 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs ≥ 120 g/L), number of nodal areas (> 4 vs ≤ 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (≥ 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs ≤ 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs ≥ 120 g/L), number of nodal areas (> 4 vs ≤ 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (≥ 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

Thalidomide has significant clinical activity in patients with multiple myeloma. However, its activity against other lymphoid tumors is unknown. The authors reported their experience with thalidomide in patients with recurrent/refractory non-Hodgkin lymphoma and in patients with Hodgkin disease. Nineteen patients (median age, 62 years) who had undergone a median of 5 previous treatment regimens were treated with escalating doses of thalidomide (200–800 mg per day) until disease progression or prohibitive toxicity was observed. The authors measured serum levels of angiogenesis factors before and after treatment. One patient (5%) with evidence of recurrent gastric mucosa—associated lymphoid tissue lymphoma achieved a complete response, and 3 patients (16%) achieved stable disease. The current study suggests that thalidomide has limited single-agent activity in heavily pretreated patients with recurrent or refractory lymphoma. Cancer 2004. © 2004 American Cancer Society.

The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m²/day × 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1–5, cytosine arabinoside at a dose of 2000 mg/ m² i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m²/day × 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m² i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2–3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m²/day for Cohort 1 with subsequent increments of 0.3 g/m²/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m²/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m²/day. Thus, DLT occurred at a dose of 1.5 g/m²/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity. Cancer 2003;98:1021–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11627

To explore the potential role of infiltrating benign B cells in classic Hodgkin disease (HD) lesions in supporting the survival of malignant Hodgkin and Reed–Sternberg (H/RS) cells, the authors initiated a pilot study of rituximab. Rituximab is used to primarily deplete normal B cells from HD lesions. Patients with recurrent, classic HD who had received a minimum of two prior treatment regimens, regardless of whether H/RS cells expressed CD20, were treated with 6 weekly doses of 375 mg/m² rituximab to selectively deplete infiltrating benign B cells. Objective tumor response was determined 3 weeks after completion of the last dose of rituximab and every 3 months thereafter. Serum samples were collected from patients before they started rituximab therapy and 3 weeks after the final course of rituximab. Serum cytokine levels of interleukin 6 (IL-6), IL-10, IL-12, IL-13, and interferon γ were determined using commercially available enzyme-linked immunosorbent assay kits. Twenty-two patients with nodular sclerosis histology were evaluable for treatment response. Five patients (22%) achieved partial or complete remission that lasted for a median of 7.8 months (range, 3.3–14.9 months). Remissions were observed in patients only at lymph node and splenic sites, but not at extranodal sites, and were irrespective of CD20 expression by H/RS cells. Furthermore, systemic (B) symptoms resolved in six of seven patients after therapy. In two patients, partial remissions were associated with a decline in serum IL-6 levels. The current data suggest that rituximab therapy in patients with recurrent, classic HD can alter serum IL-6 cytokine levels, can improve B symptoms, and may result in clinical remissions. Cancer 2003;98:310–4. © 2003 American Cancer Society. DOI 10.1002/cncr.11511

The reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15–30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown. From March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow-up evaluations. Only 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients. Gastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study. Cancer 2003;97:586–91. © 2003 American Cancer Society. DOI 10.1002/cncr.11096

Treatment for patients with stage IV indolent lymphoma ranges from watchful waiting to intensive chemotherapy and stem cell transplantation. In this trial we compared 2 induction regimens followed by 1 year of interferon maintenance therapy. Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP). Maintenance interferon/dexamethasone was given for 1 year in both treatment arms. Endpoints were comparisons of remission rates, survival, failure-free survival (FFS), molecular response rates, and toxicities. One hundred forty-two patients with previously untreated stage IV indolent lymphoma were evaluable (73 on FND; 69 on ATT). The overall response rates were 97% for FND and 97% for ATT (P= .9). The median follow-up is 5.9 years. The 5-year survival rates were 84% with FND and 82% with ATT (P= .9); the 5-year FFS rates were 41% with FND and 50% with ATT (P= .02). In a multivariate analysis, factors predicting for longer FFS were β2-microglobulin less than 3 mg/L (P= .01) and ATT treatment (P= .03). ATT was associated with a substantially higher rate of grade 3-4 toxicities than FND. In conclusion, both regimens were associated with high rates of response and survival. ATT was associated with substantially longer FFS, but it was more toxic than FND.

Treatment for patients with stage IV indolent lymphoma ranges from watchful waiting to intensive chemotherapy and stem cell transplantation. In this trial we compared 2 induction regimens followed by 1 year of interferon maintenance therapy. Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP). Maintenance interferon/dexamethasone was given for 1 year in both treatment arms. Endpoints were comparisons of remission rates, survival, failure-free survival (FFS), molecular response rates, and toxicities. One hundred forty-two patients with previously untreated stage IV indolent lymphoma were evaluable (73 on FND; 69 on ATT). The overall response rates were 97% for FND and 97% for ATT (P = .9). The median follow-up is 5.9 years. The 5-year survival rates were 84% with FND and 82% with ATT (P = .9); the 5-year FFS rates were 41% with FND and 50% with ATT (P = .02). In a multivariate analysis, factors predicting for longer FFS were β2-microglobulin less than 3 mg/L (P = .01) and ATT treatment (P = .03). ATT was associated with a substantially higher rate of grade 3-4 toxicities than FND. In conclusion, both regimens were associated with high rates of response and survival. ATT was associated with substantially longer FFS, but it was more toxic than FND.

To describe the clinical features and histologic classification of orbital lymphoma secondary to systemic non-Hodgkin lymphoma, to evaluate the efficacy of various treatment modalities for controlling the orbital component of disease, and to analyze vision-related outcomes.

After completing this course, the reader will be able to: Describe subsets of patients with indolent lymphoma for whom cure may be a realistic goal.Describe the ways by which the polymerase chain reaction for bcl‐2 can be utilized to monitor patients with follicular lymphoma.Identify immunotherapy approaches that have shown promising results for patients with indolent lymphoma. Describe subsets of patients with indolent lymphoma for whom cure may be a realistic goal. Describe the ways by which the polymerase chain reaction for bcl‐2 can be utilized to monitor patients with follicular lymphoma. Identify immunotherapy approaches that have shown promising results for patients with indolent lymphoma. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com In the era of conventional alkylating agent‐based chemotherapy, advanced stage indolent lymphoma has been considered incurable. The failure of our traditional therapies to cure these patients, coupled with the indolent course of the disease and the elderly population affected, has fostered a nihilistic attitude about the treatment of these diseases. Twenty years ago, in the absence of interesting alternatives to alkylating agents, judicious use and reuse of alkylators was perhaps the best we could do. There are now many reasons for optimism and excitement in the treatment of these diseases, including the availability of promising agents such as interferon‐α, the nucleoside analogues, and rituximab. Radioimmunotherapy will also likely play a role in future therapy programs. Allogeneic stem cell transplantation is a high‐risk approach that is not an option for all patients, but it has the potential to cure patients, even in the setting of relapse. Mini‐allogeneic transplantation may permit an approach to allogeneic transplantation that is better tolerated than standard transplant strategies. In addition to these therapy options, biological insights have provided new options for monitoring patients. Molecular monitoring (polymerase chain reaction for bcl‐2) is a stringent measure of short‐term treatment efficacy, and one that correlates with durability of remission, i.e., it is a surrogate marker by which to judge treatment efficacy. There used to be a limited number of conventional treatment approaches, which consistently failed. The pendulum has swung. There are now many promising new options. It is time to plan and conduct trials that are geared for success.

One result of recent discussions on the notion of function is that the appeal to the function of something in order to explain why it is there and what it is, presupposes (willingly or not) that some system particularly relevant to the function bearer has a good. Some recent analyses of what it means to have a good trace having a good back to having a function. Two such attempts are examined and compared to a more traditional analysis. An anachronistic version of Aristotle, involving the self-production of the beneficiary, is recommended as a better starting point for a naturalistic reconstruction of the subject of benefit.

This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m2given daily for 5 days or 30 mg/m2daily for 3 days) and intravenous cyclophosphamide (1 g/m2given daily for 2 days or 750 mg/m2daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.

This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m2 given daily for 5 days or 30 mg/m2daily for 3 days) and intravenous cyclophosphamide (1 g/m2given daily for 2 days or 750 mg/m2 daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.

The authors previously reported that central lymphatic irradiation (CLI) can induce molecular remission in patients with Stage I–III follicular lymphoma, as measured by polymerase chain reaction analysis for t(14;18) (q32;q21). Hematologic toxicity has been considered a major consequence of CLI. This study was undertaken to analyze the patterns of hematologic recovery after CLI. Thirty-three patients with Stage I–III follicular lymphoma were treated with CLI between January 1993 and February 1998. CLI consisted of irradiation to mantle, upper two-thirds of abdomen, and pelvic fields. Each field was treated to 30.0–30.6 grays (Gy) at 1.5–1.8 Gy per fraction, with a boost to 36.0–39.6 Gy at the same rate to the sites of macroscopic disease. A break of approximately 4 weeks was given after treatment of each field. Twenty-four patients who were followed for a minimum of 1 year from the end of CLI form the basis of this analysis. Fourteen patients were male. Three patients had Stage I disease, 6 patients had Stage II disease, and 15 patients had Stage III disease. The International Prognostic Index (IPI) for malignant lymphoma was 0 for 5 patients, 1 for 13 patients, and 2 for 6 patients. The Eastern Cooperative Oncology Group performance status was 0 for 21 patients and 1 for 3 patients. The median values for their pretreatment characteristics were as follows: age, 60 years (range, 34–73 years); height, 173 cm (range, 155–193 cm); weight, 79 kg (range, 57–107 kg); body surface area (BSA), 1.95 m² (range, 1.61–2.31 m²); bone marrow cellularity, 27%(range, 2–75%), platelet count, 233,000/mm³ (range, 139,000–339,000/mm³), white blood cell (WBC) counts, 6400/mm³ (range, 4200–10,900/mm³); and hemoglobin, 14.5 mg/dL (range, 11.8 –16.6 mg/dL). The median duration of CLI was 159 days (range, 137–345 days). Ten patients had cardiovascular disease. The number of sites receiving a boost dose of ≥ 36.0 Gy was 0 sites in 1 patient, 1 site in 6 patients, 2 sites in 11 patients, 3 sites in 5 patients, and 4 sites in 1 patient. The platelet, hemoglobin, and WBC counts were followed every 3 months after completion of CLI. These counts were normalized to the pretreatment counts for statistical analyses. Univariate and multivariate analyses were performed to investigate the correlations between patient factors and hematologic status at 1 year posttreatment. Pearson correlation analysis was used for the continuous factors (patient age, height, weight, BSA, bone marrow cellularity, and duration of CLI), and the Mann–Whitney test was used for categoric factors (IPI, gender, performance status, stage, number of sites receiving ≥ 36.0 Gy, and presence or absence of cardiovascular disease). There was continued recovery, essentially approaching the pretreatment levels, over 3 years for platelet, WBC, and hemoglobin counts. Factors that were associated significantly with normalized platelet counts at 1 year by univariate analyses were age (P = 0.015) and cardiovascular disease (P = 0.041). Age was the only significant factor by multivariate analyses, with older patients having lower platelet counts at 1 year posttreatment. No factors were found that were associated significantly with 1-year normalized WBC or hemoglobin levels by either univariate or multivariate analyses. All three of the hematologic components (platelets, WBC, and hemoglobin) essentially recover after patients undergo CLI over a 3-year period. Older age was the only significant adverse factor that affected the platelet recovery, as detected by multivariate analysis. Cancer 2001;92:1074–9. © 2001 American Cancer Society.

OBJECTIVES

This study was designed to determine response, outcome, and patterns of failure of patients with non-Hodgkin's lymphoma who presented with a testicular mass. Consecutive patients presenting to M.D. Anderson Cancer Center between 1969 and 1999 treated with doxorubicin- based regimens and with radiotherapy and/or intrathecal therapy were considered for this study. We identified 43 patients whose median age was 61 years. Ann Arbor stage (AAS) was I in 22 patients, II in 7 patients, III in 1 patient, and IV in 13 patients. All 43 patients had intermediate-grade lymphomas according to the Working Formulation, and all 31 tumors assessed immunophenotypically were large B-cell lymphoma according to the World Health Organization classification. The International Prognostic Index score was = 2 in 18 patients (42%). Thirty-four patients achieved complete remission, 19 of whom relapsed, and 5 failed initial therapy. At 10 years, progression- free survival (PFS) was 20% ± 9% and survival was 33% ± 9%. Progression-free survival for patients with AAS I/II vs. III/IV was 36% ± 13% vs. 0%, respectively (P= 0.004). At 10 years, the actuarial probability of failure in the central nervous system was 34% ± 9% and was 21% ± 9% in contralateral testis. Using the intent-to-treat method, patients receiving cyclophosphamide/doxorubicin/vincristine/ prednisone (CHOP), with additional scrotal radiotherapy and intrathecal methotrexate, had a 5-year PFS of 91% ± 9% vs. 30% ± 15% vs. 41% ± 12% for those receiving only one or neither of these additional modalities (P= 0.053). Doxorubicin-based regimens alone appear unable to cure most patients with lymphoma involving the testis, but CHOP with prophylactic intrathecal therapy and adjuvant scrotal radiotherapy appears promising. This should be confirmed with prospective clinical trials and longer follow-up.

We assessed left ventricular systolic and diastolic performance during and after prolonged exercise under controlled conditions in a group of healthy, trained men. Previous studies have examined the effects of prolonged effort on left ventricular function, yet it remains unclear whether or not left ventricular dysfunction (e.g. cardiac fatigue) can be produced under such conditions. We studied 15 healthy men, aged 27±1 years (mean±S.E.M.). Subjects exercised on bicycles at a constant work rate (60% of maximum oxygen uptake per min) for 150 min. Measurements of gas exchange, blood pressure and haematocrit were obtained, concurrent with the assessment of left ventricular function using equilibrium radionuclide angiography, at rest, during exercise (every 30 min) and after 30 min of recovery. Fluid replacement was provided and monitored during the exercise period. The baseline resting and exercise ejection fractions were 66±2% and 78±2% respectively. During exercise, subjects consumed 1816±136 ml of fluid, and the haematocrit had increased at 120 min of exercise (from 47.2%±0.6 to 49.9±0.8%; P < 0.05). There was no change in either systolic or diastolic blood pressure throughout the exercise period, but heart rate drifted upwards from 141±2 beats/min after 30 min to 154±3 beats/min after 150 min (P < 0.05). There was a small decline (8%; P < 0.05) in end-diastolic volume at 150 min. No changes were observed in left ventricular ejection fraction, the pressure/volume ratio or end-systolic volume. After 30 min of sitting in recovery, heart rate was still higher than the pre-exercise value (84±3 compared with 69±2 beats/min; P < 0.05), as were measures of peak filling rate and time to peak filling (P < 0.05). The ejection fraction in the post-exercise recovery period was similar to the pre-exercise value. The results indicate that prolonged exercise of moderate duration may not induce abnormal left ventricular systolic function or cardiac fatigue during exercise.

OBJECTIVES

The t(14;18) translocation, which involves the bcl-2oncogene, occurs in follicular lymphomas (FL) at two common sites: the major breakpoint region (MBR) and the minor cluster region (mcr). The biological and clinical significance of these breakpoints is unknown. The bcl-2breakpoint site was determined in 247 previously untreated patients (49% men; median age 52 years) with indolent FL (155 grade I, 83 grade II, and 8 grade III) to correlate it with pretreatment characteristics, response, and outcome. The bcl-2breakpoint site was determined by a polymerase chain reaction method of peripheral blood (all cases), bone marrows (149 cases), and fresh lymph node biopsy specimens (68 cases). The breakpoint site occurred at MBRin 175 cases (71%) and atmcrin 27 (11%). In 45 cases (18%), no breakpoint was detected (germline). No significant relationship was found between the rearrangements and the expression of BLC-2and BAXproteins. Patients' germline for MBRand mcrtended to present more frequently with stage IV disease and higher β2-microglobulin (β2M) levels, whereas mcr-rearranged patients presented more frequently with early stage and normal β2M. The complete response rate of germline patients was significantly lower than that of MBRand mcrpatients. An estimated 3-year failure-free survival (FFS) for mcr, MBR, and germline cases was 95%, 76%, and 57%, respectively (P< .001). Thebcl-2breakpoint site was independent of serum β2M and lactate dehydrogenase in its correlation with FFS. In conclusion, thebcl-2rearrangement site is an important prognostic factor in indolent FL, useful to identify patients who may require different treatment.

The t(14;18) translocation, which involves the bcl-2oncogene, occurs in follicular lymphomas (FL) at two common sites: the major breakpoint region (MBR) and the minor cluster region (mcr). The biological and clinical significance of these breakpoints is unknown. The bcl-2 breakpoint site was determined in 247 previously untreated patients (49% men; median age 52 years) with indolent FL (155 grade I, 83 grade II, and 8 grade III) to correlate it with pretreatment characteristics, response, and outcome. The bcl-2 breakpoint site was determined by a polymerase chain reaction method of peripheral blood (all cases), bone marrows (149 cases), and fresh lymph node biopsy specimens (68 cases). The breakpoint site occurred at MBR in 175 cases (71%) and atmcr in 27 (11%). In 45 cases (18%), no breakpoint was detected (germline). No significant relationship was found between the rearrangements and the expression of BLC-2 and BAXproteins. Patients’ germline for MBR and mcr tended to present more frequently with stage IV disease and higher ß2-microglobulin (ß2M) levels, whereas mcr-rearranged patients presented more frequently with early stage and normal ß2M. The complete response rate of germline patients was significantly lower than that of MBR and mcr patients. An estimated 3-year failure-free survival (FFS) for mcr, MBR, and germline cases was 95%, 76%, and 57%, respectively (P?

Purpose: Evaluate response, duration of response, and toxicity of paclitaxel in combination with other drugs known to be effective in non-Hodgkin's lymphoma (NHL). Methods: Thirty-eight patients with relapsed/refractory NHL who had been exposed to doxorubicin as well as the cytarabine-cisplatin combinations received Mesna 1.33 gm/M2/D daily days 1, 2, 3 IV over 1 hour; ifosfamide 1.33 gm/M2/D daily days 1, 2, 3 IV over 1 hour (same bag); Novantrone 8 mg/M2/D IV day 1; and Taxol 27.5 mg/M2/D daily days 1, 2, 3, 4 by continuous 24-hour intravenous infusion. Premedication for Taxol included dexamethasone, diphenhydramine, and cimetidine on day 1. Results: Of 35 evaluable patients, 9 (26%) achieved a complete response and 7 (20%) a partial response for a total response rate of 46%. The median failure-free and overall survival times were 2 and 10 months, respectively. Major toxicity was hematologic with a median absolute neutrophil nadir of 196/mm3. Only 10% of the cycles were associated with a grade 3−4 infection. Conclusion: MINT is an active and safe regimen for relapsed/refractory NHL that have failed both an Adriamycin-containing regimen and a cytarabine/cisplatin-containing regimen.

Two hundred and fifty previously untreated adult patients with diffuse large-cell lymphomas were treated with a chemotherapy combination of cyclophosphamide, adriamycin, vincristine, prednisone, and low-dose bleomycin (CHOP-Bleo) with or without radiotherapy between 1974 and 1984. The 10-year survival rates for patients with Ann Arbor stages II, III, or IV disease of 55%, 42%, and 40%, respectively, were not significantly different. However, the survival rate of 76% for patients with stage I disease was clearly better. Factors more indicative of prognosis than stage, as found by univariant analysis, were tumor burden, serum lactic dehydrogenase level (LDH), age, and constitutional symptoms. From these, a multivariant analysis selected tumor burden, LDH level, and age as major independent factors for predicting survival (P≪ .001). A prognostic risk model constructed on the basis of tumor burden and LDH levels identified four distinct risk groups (A, B, C, D) with 10-year survival rates of 85%, 66%, and 43% for A, B, and C. No patient in group D survived 10 years. These risk groups also had a strong correlation with complete remission rates and with relapse rates. Thus this model proved more effective for identifying patient populations according to their expected responses, durations of remission, and survivals than the Ann Arbor staging system. Detailed information supporting the use of this system for predicting prognosis and for treatment selection for patients with diffuse large-cell lymphomas is provided. © 1989 by Grune & Stratton. Inc.