Lymphoma survivors after high-dose therapy with autologous stem-cell transplant (HDT-ASCT) are at risk of several late effects, which might impair their health-related quality of life (HRQoL). We ...assessed the total late effect burden in this population, and how it affects HRQoL. All lymphoma survivors treated with HDT-ASCT as adults in Norway between 1987 and 2008 were identified, and 271 (68%) attended both a comprehensive clinical assessment and completed a questionnaire. Severity of 45 conditions in 12 organ-system categories were graded as mild, moderate, severe or life-threatening, according to a modified version of CTCAEv4.03. At a median of 8 years after HDT-ASCT, 98% of survivors had at least one moderate or more severe late effect and 56% had severe or life-threatening late effects. Fourteen percent had low, 39% medium and 47% high late effect burden, defined as having moderate or more severe late effects in 0-1, 2-3 and >3 organsystems, respectively. Female sex, increasing age, B-symptoms at diagnosis and >1 treatment line prior to HDT-ASCT were independently associated with having high late effect burden. The survivors had significantly poorer physical and mental HRQoL assessed by the Short Form-36 compared to age- and sex-matched controls. The prevalence of poor physical and mental HRQoL increased with higher late effect burden (both P<0.001), and the low burden group had better physical HRQoL than controls (P<0.001). In conclusion, lymphoma survivors after HDT-ASCT have impaired HRQoL, seemingly driven by a high late effect burden. This highlights the importance of prevention, regular assessments for early detection and treatment of late effects and modifiable risk factors.
To examine the effects of a computer-assisted, interactive tailored patient assessment (ITPA) tool in oncology practice on: documented patient care, symptom distress, and patients' need for symptom ...management support during treatment and rehabilitation.
For this repeated measures clinical trial at a university hospital in Norway, 145 patients starting treatment for leukemia or lymphoma were randomly assigned to either an intervention (n=75) or control group (n=70). Both groups used the ITPA for symptom assessments prior to inpatient and outpatient visits for up to one year. The assessment summary, which displayed patients' self-reported symptoms, problems, and distress in rank-order of the patient's need for support, was provided to physicians and nurses in the intervention group only but not in the control group.
Significantly more symptoms were addressed in the intervention group patient charts versus those of the control group. Symptom distress in the intervention group decreased significantly over time in 11 (58%) of 19 symptom/problem categories versus 2 (10%) for the control group. Need for symptom management support over time also decreased significantly more for the intervention group than the control group in 13 (68%) symptom categories.
This is the first study to show that an ITPA used in an interdisciplinary oncology practice can significantly improve patient-centered care and patient outcomes, including reduced symptom distress and reduced need for symptom management support.
Molecular diagnosis of Burkitt's lymphoma Dave, Sandeep S; Fu, Kai; Wright, George W ...
The New England journal of medicine,
06/2006, Letnik:
354, Številka:
23
Journal Article
Recenzirano
Odprti dostop
The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling ...could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.
Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.
A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt's lymphoma, suggesting they represent cases of Burkitt's lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt's lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens.
Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt's lymphoma from diffuse large-B-cell lymphoma.
Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis ...to develop a molecular predictor of the length of survival.
Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens.
Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells.
The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Palliative radiotherapy (PRT) comprises half of all radiotherapy use and is an effective and important treatment modality for improving quality of life in incurable cancer patients. We have described ...the use of PRT in Norway and aimed to identify and quantify the impact of factors associated with PRT utilization.
Population-based data from the Cancer Registry of Norway identified 25,281 patients who died of cancer, 1 July 2009-31 December 2011. Additionally, individual-level data on socioeconomic status and community-level data on travel distance were collected. The proportion of patients who received PRT in the last two years of life (PRT
2Y
) was calculated, and multivariable logistic regression was used to determine factors that influenced the PRT
2Y
. Analyses of geographic variation in PRT use were also performed for the time period 2012-2016.
PRT
2Y
for all cancer sites combined was 29.6% with wide geographic variations (standardized inter-county range; 21.8-36.6%). Female gender, increasing age at death, certain cancer sites, short survival time, and previous receipt of curative radiotherapy were associated with decreased odds of receiving PRT. Patients with low education, those living in certain counties, or with travel distances 100-499 km, were also less likely to receive PRT. Patients with low household income (adjusted odds ratio (OR) = 0.63; 95% confidence interval (CI) = 0.56-0.72) and those diagnosed in hospitals without radiotherapy facility (OR = 0.70; 95% CI = 0.64-0.77) had especially low likelihood of receiving PRT. Significant inter-county variation in use of PRT remained during the time period 2012-2016.
Despite a publicly funded, universal healthcare system with equity as a stated health policy aim, utilization of PRT in Norway is significantly associated with factors such as household income and availability of radiotherapy facility at the diagnosing hospital. Even after adjustments for relevant factors, unexplained geographic variations in PRT utilization exist.
To determine, in a randomized clinical trial, whether high-dose therapy (HDT) followed by autologous stem-cell transplantation is more effective than standard treatment with regard to ...progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular non-Hodgkin's lymphoma; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS.
Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P).
Between August 1993 and April 1997, 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were.0037 and.079, respectively. For PFS, the hazard ratios (95% CIs) for U versus C, P versus C, and P versus U were 0.33 (0.16 to 0.70), 0.38 (0.19 to 0.79), and 1.02 (0.51 to 2.05), respectively. The hazard ratio (95% CI) for C versus U + P was 0.30 (0.15 to 0.61). Hazard ratios (95% CIs) for OS were 0.43 (0.18 to 1.06), 0.43 (0.18 to 1.02), and 0.72 (0.32 to 1.63). For C versus U + P, the hazard ratio (95% CI) was 0.40 (0.18 to 0.89). Kaplan-Meier estimates (95% CIs) of 2-year PFS for C, U, and P were 26% (8% to 44%), 58% (37% to 79%), and 55% (34% to 75%), respectively. OS at 4 years for C, U, and P are 46% (25% to 67%), 71% (52% to 91%), and 77% (60% to 95%) respectively.
HDT significantly improves PFS and OS. There is no clear evidence of benefit through purging.
Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression ...profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.
The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a ...molecular predictor of survival.
Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index.
Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators.
DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma.
Summary Background 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. Methods 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. Findings 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). Interpretation 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. Funding Roche, Basel, Switzerland (M39045).
To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission ...therapy in adults with lymphoblastic lymphoma.
One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization.
Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval CI, 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71).
The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.
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