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Patients with follicular lymphoma may survive for periods ranging from less than a year to several decades. In this study, DNA-microarray analysis of gene expression in specimens of follicular lymphoma showed that two genetic signatures predicted the length of survival with a high degree of accuracy. Surprisingly, one signature consisted of genes that are typically expressed in normal T cells, and the other consisted of genes expressed in monocytes and dendritic cells. DNA-microarray analysis of gene expression in specimens of follicular lymphoma showed that two genetic signatures predicted survival with a high degree of accuracy. Follicular lymphoma is the second most common form of non-Hodgkin's lymphoma, accounting for about 22 percent of all cases. 1 The clinical course of follicular lymphoma is variable: in some patients the disease is indolent and slowly progressive over a period of many years, with waxing and waning lymphadenopathy, whereas in others the disease progresses rapidly, often with transformation to aggressive lymphoma and early death. 2 , 3 Management includes observation, chemotherapy, hematopoietic stem-cell transplantation, and immunologic therapies based on antibodies to B cells 4 – 7 or idiotype vaccines. 8 – 10 There is no conclusive evidence that any of these approaches offers a clinically significant . . .

The definition and role of bulky disease in young patients (ie, aged 18–60 years) with good-prognosis diffuse large-B-cell lymphoma (DLBCL), who have been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-like chemotherapy with or without rituximab, remain controversial. We aimed to assess the effect of maximum tumour diameter (MTD) in these patients. Patients from the MInT (Mabthera International Trial Group) study were eligible. We analysed event-free (EFS) and overall survival (OS) after CHOP-like chemotherapy with or without rituximab, according to MTD, by Martingale residual analyses and Cox regression models. Radiotherapy was given to sites of primary bulky disease according to national standards, and to primary extranodal disease at physician discretion. The primary endpoint was EFS and the secondary endpoint was OS. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00064116. Of the 824 patients enrolled in the MInT study, the informed-consent form of one patient was missing, leaving 823 patients evaluable for intention-to-treat analysis. Data on MTD of involved sites were available for 802 patients. Martingale residual analysis showed an adverse prognostic effect of MTD on EFS and OS, which increased linearly. In a multivariable analysis with MTD as a linear regression variable, the effect of MTD was significant after CHOP-like treatment alone for EFS (hazard ratio 1·090 [95% CI 1·051–1·130], p<0·0001) and OS (1·119 [1·057–1·184], p=0·0001), and after CHOP-like treatment and rituximab for OS (1·089 [1·003–1·183], p=0·043), but not for EFS (1·044 [0·991–1·099], p=0·103). For CHOP-like treatment alone, 3-year EFS ranged from 78·2% (MTD <5·0 cm, 95% CI 68·3–85·4) to 41·3% (MTD ≥10·0 cm, 31·8–50·4). For CHOP-like treatment and rituximab, 3-year EFS ranged from 83·2% (MTD <5·0 cm, 72·8–89·9) to 72·7% (MTD ≥10·0 cm, 63·8–79·7). With CHOP-like treatment alone, 3-year OS decreased from 92·9% (MTD <5·0 cm, 84·9–96·8) to 73·5% (MTD ≥10·0 cm, 63·9–81·0); for CHOP-like treatment and rituximab, 3-year OS decreased from 98·0% (MTD <5·0 cm, 92·2–99·5) to 85·2% (MTD ≥10·0 cm, 77·0–90·6). For CHOP-like treatment, any cut-off point between 5·0 cm and 10·0 cm separated two populations with a significant EFS difference (p<0·0001 for all log-rank tests) and OS difference (p≤0·003 for all log-rank tests). For CHOP-like treatment and rituximab, only a cut-off point of 10·0 cm separated two populations with a significant EFS difference (log-rank p=0·047), but any cut-off point of 6·0 cm or more separated two populations with a significant OS difference (log-rank p values 0·0009–0·037). Rituximab decreased, but did not eliminate the adverse prognostic effect of MTD in young patients with good-prognosis DLBCL. Due to the linear prognostic effect of MTD on outcome, arbitrary cut-off points for bulky disease can be set between 5·0 cm and 10·0 cm, depending on clinical considerations. Based on this study, a cut-off point of 10·0 cm might be a suitable margin in the rituximab era to delineate those patients with bulky disease. Roche, Basel, Switzerland (M39045).

In a large group of diffuse large-B-cell lymphomas, DNA microarrays identified three patterns of gene expression that were correlated with the likelihood of survival after chemotherapy. Individual genes within these patterns formed molecular signatures that had an even stronger correlation with survival after chemotherapy. The predictive power of the molecular signatures was independent of the international prognostic index. In diffuse large-B-cell lymphomas, three patterns correlated with the likelihood of survival. Diffuse large-B-cell lymphoma, the most common type of lymphoma in adults, can be cured by anthracycline-based chemotherapy in only 35 to 40 percent of patients. 1 The multiple unsuccessful attempts to increase this rate 2 suggest that diffuse large-B-cell lymphoma actually comprises several diseases that differ in responsiveness to chemotherapy. Support for this idea comes from a study of gene-expression profiles, which identified two subgroups of diffuse large-B-cell lymphoma that had different outcomes after multiagent chemotherapy. 3 The germinal-center B-cell–like subgroup expressed genes characteristic of normal germinal-center B cells and were associated with a good outcome, whereas the activated B-cell–like subgroup expressed genes . . .

The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-term effects. In the randomised open-label MInT study, patients from 18 countries (aged 18–60 years with none or one risk factor according to the age-adjusted International Prognostic Index [IPI], stage II–IV disease or stage I disease with bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites received additional radiotherapy. Randomisation was done centrally with a computer-based tool and was stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component. Patients and investigators were not masked to treatment allocation. The primary endpoint was event-free survival. Analyses were by intention to treat. This observational study is a follow-up of the MInT trial, which was stopped in 2003, and is registered at ClinicalTrials.gov, number NCT00400907. The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0·03–119), 6-year event-free survival was 55·8% (95% CI 50·4–60·9; 166 events) for patients assigned to chemotherapy alone and 74·3% (69·3–78·6; 98 events) for those assigned to chemotherapy plus rituximab (difference between groups 18·5%, 11·5–25·4, log-rank p<0·0001). Multivariable analyses showed that event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only. After chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free survival 84·3% [95% CI 74·2–90·7] vs 71·0% [65·1–76·1], log-rank p=0·005). 18 (4·4%, 95% CI 2·6–6·9) second malignancies occurred in the chemotherapy-alone group and 16 (3·9%, 2·2–6·2) in the chemotherapy and rituximab group (Fisher's exact p=0·730). Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone. Hoffmann–La Roche.

Background: Cardiorespiratory fitness as measured by peak oxygen consumption (VO 2peak ) is a strong predictor of longevity and may be compromised by anticancer therapy, inactivity, and smoking. We compared VO 2peak among lymphoma survivors (LSs) with reference data from healthy sedentary subjects, after a 10.2-year (mean) follow-up post high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We further examined the association between VO 2peak and treatment, physical activity, smoking, pulmonary, and cardiac function. Methods: Lymphoma survivors treated with HDT-ASCT in Norway 1987–2008 were eligible. VO 2peak was assessed by cardiopulmonary exercise testing. Pulmonary function testing and echocardiography were also conducted. Data on treatment, physical activity, and smoking were collected from hospital records and questionnaires. VO 2peak was compared with age–sex predicted reference data. Linear regression was used to associate clinical factors with VO 2peak cross-sectionally. Results: A total of 194 LSs without heart failure were studied. Mean VO 2peak was 4.5% and 7.7% below norms in females and males, respectively. Twenty-two percent had impaired (<80% predicted) VO 2peak . Decreasing VO 2peak was associated with impaired diffusion capacity and current smoking, while physical activity level and VO 2peak were positively associated. Conclusion: We suggest increased attention towards physical activity counseling and smoking cessation advice to preserve cardiorespiratory fitness in LSs after HDT-ASCT. Patients with impaired diffusion capacity may benefit from subsequent monitoring to detect pulmonary vascular diseases.

The role of rituximab in combination with different CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined. We aimed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients. 824 patients who were from 18 countries; aged 18–60 years; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index (IPI), stage II–IV disease, or stage I disease with bulk were enrolled. These patients were randomly assigned to six cycles of CHOP-like chemotherapy and rituximab (n=413) or to six cycles of CHOP-like chemotherapy alone (n=411). Bulky and extranodal sites received additional radiotherapy. The primary endpoint was event-free survival; secondary endpoints were response, progression under therapy, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat and per protocol. This trial is registered at http://www.clinicaltrials.gov, NCT 00064116. After a median follow-up of 34 months (range 0·03–61), patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone (79% [95% CI 75–83] vs 59% [54–64]; difference between groups 20% [13–27], log-rank p<0·0001), and had increased 3-year overall survival (93% [90–95] vs 84% [80–88]; difference between groups 9% [3–13], log-rank p=0·0001). Event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI: after chemotherapy and rituximab, a favourable subgroup (ie, IPI=0, no bulk) could be defined from a less-favourable subgroup (ie, IPI=1 or bulk, or both). Groups did not differ in the frequency of adverse events. Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients.

A method involving patterns of gene expression was used to distinguish all cases of classic Burkitt's lymphoma from various forms of diffuse large-B-cell lymphoma, which had been verified by an expert panel of hematopathologists. Difficulties in the distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma may be resolved by the use of gene-expression patterns. Difficulties in the distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma may be resolved by the use of gene-expression patterns. Burkitt's lymphoma is an aggressive B-cell lymphoma characterized by a high degree of proliferation of the malignant cells and deregulation of the c -myc gene. 1 Distinguishing between Burkitt's lymphoma and diffuse large-B-cell lymphoma is critical because the management of these two diseases differs. Whereas relatively low-dose chemotherapy regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) are typically used to treat diffuse large-B-cell lymphoma, they are inadequate for Burkitt's lymphoma, 2 , 3 for which intensive chemotherapy regimens are required. 4 – 8 Furthermore, prophylactic intrathecal chemotherapy or systemic chemotherapy that crosses the blood–brain barrier is unnecessary in most cases of diffuse large-B-cell lymphoma; . . .

Background The role of rituximab in combination with different CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined. We aimed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients. Methods 824 patients who were from 18 countries; aged 18–60 years; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index (IPI), stage II–IV disease, or stage I disease with bulk were enrolled. These patients were randomly assigned to six cycles of CHOP-like chemotherapy and rituximab (n=413) or to six cycles of CHOP-like chemotherapy alone (n=411). Bulky and extranodal sites received additional radiotherapy. The primary endpoint was event-free survival; secondary endpoints were response, progression under therapy, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat and per protocol. This trial is registered at http://www.clinicaltrials.gov, NCT 00064116. Findings After a median follow-up of 34 months (range 0·03–61), patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone (79% [95% CI 75–83] vs 59% [54–64]; difference between groups 20% [13–27], log-rank p<0·0001), and had increased 3-year overall survival (93% [90–95] vs 84% [80–88]; difference between groups 9% [3–13], log-rank p=0·0001). Event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI: after chemotherapy and rituximab, a favourable subgroup (ie, IPI=0, no bulk) could be defined from a less-favourable subgroup (ie, IPI=1 or bulk, or both). Groups did not differ in the frequency of adverse events. Interpretation Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients. Background The role of rituximab in combination with different CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined. We aimed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients. Methods 824 patients who were from 18 countries; aged 18–60 years; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index (IPI), stage II–IV disease, or stage I disease with bulk were enrolled. These patients were randomly assigned to six cycles of CHOP-like chemotherapy and rituximab (n=413) or to six cycles of CHOP-like chemotherapy alone (n=411). Bulky and extranodal sites received additional radiotherapy. The primary endpoint was event-free survival; secondary endpoints were response, progression under therapy, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat and per protocol. This trial is registered at http://www.clinicaltrials.gov, NCT 00064116. Findings After a median follow-up of 34 months (range 0·03–61), patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone (79% [95% CI 75–83] vs 59% [54–64]; difference between groups 20% [13–27], log-rank p<0·0001), and had increased 3-year overall survival (93% [90–95] vs 84% [80–88]; difference between groups 9% [3–13], log-rank p=0·0001). Event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI: after chemotherapy and rituximab, a favourable subgroup (ie, IPI=0, no bulk) could be defined from a less-favourable subgroup (ie, IPI=1 or bulk, or both). Groups did not differ in the frequency of adverse events. Interpretation Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients.

Høydosebehandling med autolog stamcellestøtte (HMAS) er rutinebehandling hos selekterte grupper av pasienter med malignt lymfom og myelomatose. Hva er kostnadene ved denne type behandling? I perioden mai 2001-desember 2001 utførte vi en prospektiv kostnadsanalyse av behandlingsforløp som grovt kan deles i 3 faser: 1) den tumorreduserende kjemoterapifasen, 2) fasen med mobilisering, høsting og nedfrysing av autologe stamceller og 3) selve høydosefasen (HMAS-fasen). 30 pasienter med myelomatose ble fulgt ved tre forskjellige universitetssykehus og 10 pasienter med lymfom ble fulgt ved det fjerde sykehuset. Direkte pasientrelaterte kostnader ble registrert daglig. Indirekte kostnader ble fordelt på pasientene basert på estimater og ut fra forhåndsdefinerte fordelingsnøkler fra relevante avdelinger. Alle kostnadsdata ble beregnet i 2001 priser. Den gjennomsnittlige totale kostnaden for alle tre faser var kr. 306 904 kr (variasjonsbredde 244 035-379 127). Vi fant en statistisk signifikant korrelasjon mellom varighet av sykehusopphold og sykehusenes kostnader i alle tre behandlingsfaser. En stor del av kostnadene i høstefasen var knyttet til medikamenter brukt til stamcellemobilisering. I høydosefasen, som var den mest kostnadskrevende fasen, var de største kostnadene knyttet til sykepleiepersonalet. Det var betydelige variasjoner i kostnader mellom sykehusene. Den gjennomsnittlige totalkostnaden var vesentlig høyere enn full DRG-pris for myelomatose og myelomatose i 2001. Sykehusene måtte selv bære differansen mellom de reelle kostnadene og DRG-prisen. Per i dag (2008) er differansen redusert da det er etablert en sideutbetaling for HMAS- behandling.