Smoking,alcohol use,obesity, and overall survival from non‐Hodgkin lymphoma

BACKGROUND:

Smoking, alcohol use, and obesity appear to increase the risk of developing non‐Hodgkin lymphoma (NHL), but to the authors' knowledge, few studies to date have assessed their impact on NHL prognosis.

METHODS:

The association between prediagnosis cigarette smoking, alcohol use, and body mass index (BMI) and overall survival was evaluated in 1286 patients enrolled through population‐based registries in the United States from 1998 through 2000. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox regression, adjusting for clinical and demographic factors.

RESULTS:

Through 2007, 442 patients had died (34%), and the median follow‐up for surviving patients was 7.7 years. Compared with never smokers, former (HR, 1.59; 95% CI, 1.12‐2.26) and current (HR, 1.50; 95% CI, 0.97‐2.29) smokers had poorer survival, and poorer survival was found to be positively associated with smoking duration, number of cigarettes smoked per day, pack‐years of smoking, and shorter time since quitting (all P <0.01). Alcohol use was associated with poorer survival (P = 0.03); compared with nonusers. Those drinking >43.1 g/week (median intake among drinkers) had poorer survival (HR, 1.55; 95% CI, 1.06‐2.27), whereas those drinkers consuming less than this amount demonstrated no survival disadvantage (HR, 1.13; 95% CI, 0.75‐1.71). Greater BMI was associated with poorer survival (P = 0.046), but the survival disadvantage was only noted among obese individuals (HR, 1.32 for BMI ≥30 vs BMI 20‐24.9; 95% CI, 1.02‐1.70). These results held for lymphoma‐specific survival and were broadly similar for diffuse large B‐cell lymphoma and follicular lymphoma.

CONCLUSIONS:

NHL patients who smoked, consumed alcohol, or were obese before diagnosis were found to have a poorer overall and lymphoma‐specific survival. Cancer 2010. © 2010 American Cancer Society.     

Health‐related quality of life among survivors of aggressive non‐Hodgkin lymphoma

BACKGROUND:

Non‐Hodgkin lymphoma (NHL) is the fifth most common cancer among men and women. Patients with aggressive NHL receive intense medical treatments that can significantly compromise health‐related quality of life (HRQOL). However, knowledge of HRQOL and its correlates among survivors of aggressive NHL is limited.

METHODS:

Self‐reported data on HRQOL (physical and mental function, anxiety, depression, and fatigue) were analyzed for 319 survivors of aggressive NHL. Survivors 2 to 5 years postdiagnosis were selected from the Los Angeles County Cancer Registry. Bivariate and multivariable methods were used to assess the influence of sociodemographic, clinical, and cognitive health‐appraisal factors on survivors' HRQOL.

RESULTS:

After accounting for other covariates, marital status was associated with all HRQOL outcomes (P < .05). Younger survivors reported worse mental function and higher levels of depression, anxiety, and fatigue (P < .01). Survivors who had more comorbid conditions or lacked private health insurance reported worse physical and mental function and higher levels of depression and fatigue (P < .05). Survivors who experienced a recurrence reported worse physical function and higher levels of depression and fatigue (P < .05). With the exception of a nonsignificant association between perceived control and physical function, greater perceptions of personal control and health competence were associated significantly with more positive HRQOL outcomes (P < .01).

CONCLUSIONS:

The current results indicated that survivors of aggressive NHL who are younger, are unmarried, lack private insurance, or experience greater illness burden may be at risk for poorer HRQOL. Cognitive health‐appraisal factors were strongly related to HRQOL, suggesting potential benefits of interventions focused on these mutable factors for this population. Cancer 2013. © 2012 American Cancer Society.     

Initial response to salvage therapy determines prognosis in relapsed pediatric Hodgkin lymphoma patients

BACKGROUND:

Pediatric Hodgkin lymphoma (HL) is a highly curable disease; however, prognostic factors for the survival of patients who develop recurrent disease have not been clearly defined.

METHODS:

This was a retrospective analysis of 50 pediatric patients with HL who relapsed or progressed between 1990 and 2006 and who were retrieved with intense cytoreductive treatment regimens followed by autologous stem cell transplantation and radiation therapy. A Cox proportional hazards model was used to determine risk factors for second treatment failure and death.

RESULTS:

The median patient age was 16.1 years (range, 4.9‐22.1 years) at the time of HL diagnosis. Fifteen patients developed progressive disease during therapy, 14 patients relapsed early, and 21 patients relapsed late. Patients who remained alive at the time of this study had been followed for a median of 4.4 years (range, 1.2‐16.6 years). The 5‐year overall survival rate for patients who had an inadequate response (n = 14) to initial salvage therapy was only 17.9% (95% confidence interval [CI], 3.1%‐42.5%) compared with 97.2% (95% CI, 81.9%‐99.6%) for patients who responded (n = 36; P < .0001). In a multivariate Cox regression analysis of overall survival, an inadequate response to initial salvage therapy was the only significant variable (hazard ratio, 43.6; 95% CI, 5.4‐354; P = .0004).

CONCLUSIONS:

The current results indicated that pediatric patients with relapsed HL who have an inadequate response after initial primary salvage chemotherapy have a very poor prognosis and should be considered for novel therapies directed at biologic or immunologic targets. Cancer 2010. © 2010 American Cancer Society.     

Primary cardiac lymphoma: an analysis of presentation, treatment, and outcome patterns

BACKGROUND:

Primary cardiac lymphoma (PCL) represents a rare subset of non‐Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication.

METHODS:

Individual patient data were obtained from defined cases of PCL (1949‐2009) and systematically analyzed.

RESULTS:

The authors report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4 factors: immune status, left ventricular involvement, presence of extra‐cardiac disease, and arrhythmia. Median overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached, respectively (HR 0.29, 95% CI, 0.13‐0.68; P = .004). LV involvement was uncommon (26%) and associated with an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12‐0.64; P = .002). Patients with extracardiac disease had shorter median OS compared with those without (6m vs 22m, HR 0.49, 95% CI, 0.26‐0.91; P = .02). Those patients with an arrhythmia of any type had a median OS that was not reached (n = 55), whereas those without rhythm disturbances (n = 41) had median OS of 6m (HR 0.51, 95% CI, 0.29‐0.91; P = .024). Overall response rate to therapy was 84%, with long‐term OS over 40%.

CONCLUSIONS:

The current study presents the largest analysis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are associated with improved survival. Cancer 2011. © 2010 American Cancer Society.     

Health status and quality of life among non‐Hodgkin lymphoma survivors

BACKGROUND:

A growing body of evidence suggests that long‐term survivors with 1 of the more common forms of adult cancer report a quality of life (QOL) similar to that in the general population. However, specific concerns have been identified (sexual dysfunction, fatigue, distress) in this population. Also, less is known concerning survivors of adult non‐Hodgkin lymphoma (NHL), a disease often marked by alternating periods of disease and remission. Therefore, in the current study, the authors compared the QOL status of individuals who reported having active NHL with the QOL status of individuals who were disease‐free short‐term survivors (STS) (2‐4 years postdiagnosis) and long‐term survivors (LTS) (≥5 years postdiagnosis).

METHODS:

Eligible survivors completed a mailed survey with validated measures, including physical and mental health status measured with the Medical Outcomes Study 36‐item Short Form, cancer‐related QOL, the Functional Assessment of Cancer Therapy‐Lymphoma module, and self‐reported impact of cancer. Other data were collected to examine as correlates.

RESULTS:

Seven hundred sixty‐one survivors identified from 2 North Carolina cancer registries participated. The average survivor was 10.4 years postdiagnosis (range, 2‐44 years postdiagnosis) and was age 62.7 years (range, 25‐92 years). Survivors with active disease (n = 109) demonstrated worse physical and mental health functioning, worse QOL, and less positive and more negative impacts of cancer compared with disease‐free survivors (n = 652; all P ≤ .01). No significant differences were observed between STS and LTS.

CONCLUSIONS:

Although survivors with NHL who had active disease reported more negative outcomes compared with off‐treatment survivors, the length of time after diagnosis did not appear to matter with regard to outcomes for STS or LTS. In addition, mixed results from comparisons with general population norms suggested the need for supportive care for this diverse survivorship group. Cancer 2009. © 2009 American Cancer Society.     

Post-treatment (not interim) positron emission tomography-computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R-HyperCVAD

BACKGROUND:

Although convincing data exist regarding the prognostic utility of positron emission tomographic (PET)‐computed tomographic (CT) imaging in Hodgkin lymphoma and diffuse large B‐cell lymphoma, its prognostic utility both during treatment and immediately after treatment have not been systematically evaluated in a large mantle cell lymphoma (MCL) patient cohort to support its use in clinical practice.

METHODS:

The authors conducted a retrospective cohort study to examine the prognostic utility of PET‐CT imaging in a uniform MCL patient cohort undergoing dose‐intensive chemotherapy (R‐HyCVAD) in the frontline setting. The primary study endpoints were progression‐free survival (PFS) and overall survival (OS). PET‐CT images were centrally reviewed for the purposes of this study using standardized response criteria.

RESULTS:

Fifty‐three patients with advanced stage MCL with PET‐CT data were identified. With median follow‐up of 32 months, 3‐year PFS and OS estimates were 76% (95% confidence interval [CI], 64%‐84%) and 84% (95% CI, 72%‐90%), respectively. Interim PET‐CT status was not associated with PFS (hazard ratio [HR], 0.9; 95% CI, 0.3‐2.7; P = .8) or OS (HR, 0.6; 95% CI, 0.1‐2.9; P = .5). Post‐treatment PET‐CT status was statistically significantly associated with PFS (HR, 5.2; 95% CI, 2.0‐13.6; P = .001) and trended toward significant for OS (HR, 2.8; 95% CI, 0.8‐9.6; P = .07).

CONCLUSIONS:

These data do not support the prognostic utility of PET‐CT in pretreatment and interim treatment settings. A positive PET‐CT after the completion of therapy identifies a patient subset with an inferior PFS and a trend toward inferior OS. Cancer 2012;3565–3570. © 2011 American Cancer Society.     

Correlation of pretransplant and early post‐transplant response assessment with outcomes after reduced‐intensity allogeneic hematopoietic stem cell transplantation for non‐Hodgkin's lymphoma

BACKGROUND:

Chemotherapy sensitivity, defined simply as at least a partial response to chemotherapy, is an important outcome predictor for non‐Hodgkin lymphoma (NHL) patients undergoing reduced‐intensity allogeneic hematopoietic stem cell transplantation (allo‐HCT). The authors hypothesized that further differentiation of chemotherapy sensitivity by specific response, complete remission (CR) versus partial remission (PR) versus stable disease (SD) versus progression of disease (PD), correlates with post‐transplant outcomes.

METHODS:

The impact of pretransplant and early (28 days) post‐transplant disease response on transplant outcomes was analyzed in 63 NHL patients treated with reduced‐intensity allo‐HCT.

RESULTS:

The 3‐year event‐free survival (EFS) and overall survival (OS) (median potential follow‐up after reduced‐intensity allo‐HCT = 58 months) for all patients was 37% and 47%, respectively. The 3‐year EFS based on pretransplant response was: CR = 50%; PR = 66%; SD = 18%; no patient with PD pretransplant reached 3‐year follow‐up. The 3‐year OS based on pretransplant response was: CR = 63%; PR = 69%; SD = 45%. The 3‐year EFS based on post‐transplant response was: CR = 57%; PR = 32%; SD = 33%; no patient with PD post‐transplant reached 3‐year follow‐up. The 3‐year OS based on post‐transplant response was: CR = 65%; PR = 43%; SD = 50%. In multivariate analyses, pretransplant response was the best predictor of EFS (P < .0001). Pretransplant response (P < .0001) and age (P = .0035) were jointly associated with OS.

CONCLUSIONS:

These data suggest that NHL patients with pretransplant SD, generally considered inappropriate candidates, may benefit from reduced‐intensity allo‐HCT, and patients with pretransplant PD should only receive this therapy in clinical trials. Cancer 2010. © 2010 American Cancer Society.     

Survival after second primary lung cancer: a population-based study of 187 Hodgkin lymphoma patients

BACKGROUND:

Lung cancer accounts for the largest absolute risk of second malignancies among Hodgkin lymphoma (HL) survivors. However, no population‐based studies have compared overall survival (OS) between HL survivors who developed nonsmall cell lung cancer (HL‐NSCLC) versus patients with first primary NSCLC (NSCLC‐1).

METHODS:

The authors compared the OS of 178,431 patients who had NSCLC‐1 and 187 patients who had HL‐NSCLC (among 22,648 HL survivors), accounting for sex, race, sociodemographic status, calendar year, and age at NSCLC diagnosis, and NSCLC histology and stage. All patients were reported to the population‐based Surveillance, Epidemiology, and End Results Program. Hazard ratios (HRs) were derived from a Cox proportional hazards model.

RESULTS:

Although the NSCLC stage distribution was similar in both groups (20% localized, 30% regional, and 50% distant), HL survivors experienced significantly inferior stage‐specific OS. For patients with localized, regional, and distant stage NSCLC, the HRs (95% confidence interval [CI]) for death among HL survivors were 1.60 (95% CI, 1.08‐2.37; P < .0001), 1.67 (95% CI, 1.26‐2.22; P = .0004), and 1.31 (95% CI, 1.06‐1.61; P = .013), respectively. Among HL‐NSCLC patients, significant associations were observed between more advanced NSCLC stage and the following variables: younger age at HL diagnosis (P = .003), younger age at NSCLC diagnosis (P = .048), and longer latency between HL and NSCLC diagnoses (P = .015).

CONCLUSIONS:

Compared with patients who had de novo NSCLC, HL survivors experienced a significant 30% to 60% decrease in OS after an NSCLC diagnosis. Further research is needed to not only elucidate the clinical‐biologic underpinnings of NSCLC after HL, including the influence of previous HL treatment, but also to define the role of lung cancer screening in selected patients. Cancer 2011;. © 2011 American Cancer Society.     

Nodular,lymphocyte‐predominant Hodgkin lymphoma

BACKGROUND:

Nodular, lymphocyte‐predominant Hodgkin lymphoma (NLPHL) represents a rare entity.

METHODS:

A clinical registry was launched from 1973 to 2003 in France. To determine the histologic transformation (HT) rate to diffuse large B‐cell lymphoma (DLBCL) and long‐term outcomes, 164 patients were selected after histologic review.

RESULTS:

The median follow‐up was 9.5 years. The high biopsy rate (85%) at each recurrence enabled the analysis of HT. The median patient age was 30 years (range, 6‐69 years), 80% of patients were men, 83% had Ann Arbor stage I/II disease, 65% had supradiaphragmatic‐disease; 27% received radiotherapy, 9% received chemotherapy, 29% received combined‐modality therapy, and 35% were followed with a watch‐and‐wait strategy. All 106 treated patients achieved complete remission and 66 patients developed disease recurrence at a median of 3.3 years (range, 0.4‐18.3 years after diagnosis). The majority of recurrences were NLPHL, but 19 patients progressed to DLBCL at a median of 4.7 years (range, 0.4‐18 years after diagnosis). The 10‐year cumulative HT rate was 12% and was found to be associated significantly with a poor prognosis. The 10‐year overall survival rate was 91%. Fourteen patients died (7 died of progressive disease, 3 died of secondary cancers, and 4 died from other causes). HT was diagnosed at a median of 4.7 years (range, 0.4‐18 years after diagnosis). The 19 patients who had HT were treated with curative intent: Nine patients received high‐dose therapy with subsequent autologous stem cell transplantation (ASCT), and 10 patients received different chemotherapy regimens. The overall survival rate after HT did not differ between patients who underwent ASCT and the others.

CONCLUSIONS:

This long‐term follow‐up study confirmed that NLPHL is a separate entity that has a favorable clinical presentation and outcome despite frequent recurrences. The current findings also emphasize the importance of biopsies at the time patients develop recurrent disease to evaluate HT. Cancer 2010. © 2009 American Cancer Society.     

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma

BACKGROUND:

Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R‐EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)‐associated, aggressive B‐cell, non‐Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity.

METHODS:

The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV‐associated NHL who received either R‐CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R‐EPOCH (n = 51; AMC034). Age‐adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/μL vs ≥100/μL), and treatment (R‐CHOP vs R‐EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event‐free survival (EFS) and overall survival (OS).

RESULTS:

Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ≥100/μL. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R‐EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P < .001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P < .01). Treatment‐associated death occurred significantly more often in patients with CD4 counts <50/μL (37% vs 6%; P < .01).

CONCLUSIONS:

The current analysis provided additional level 2 evidence supporting the use of concurrent R‐EPOCH in patients with HIV‐associated lymphoma and a CD4 count >50/μL, and the results support the design of an ongoing phase 3 trial comparing concurrent R‐EPOCH with R‐CHOP in immunocompetent patients with diffuse large B‐cell lymphoma (National Clinical Trial no. NCT00118209). Cancer 2012. © 2011 American Cancer Society.     

Pretransplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in aggressive B-cell non-Hodgkin lymphoma

BACKGROUND.

Limited data exist about the role of second‐line chemotherapy response assessed by positron emission tomography (PET) as a prognostic factor in patients with aggressive non‐Hodgkin Lymphoma (NHL) who undergo autologous stem cell transplantation (ASCT). The objective of this analysis was to investigate the main determinants of prognosis in patients with aggressive B‐cell NHL who undergo ASCT, focusing on the impact of pretransplantation PET, secondary age‐adjusted International Prognostic Index (sAA‐IPI) score, histology, and previous response to first‐line chemotherapy.

METHODS.

Seventy‐five patients with diffuse, large B‐cell lymphoma or grade 3 follicular lymphoma who were treated at the author' institution with second‐line chemotherapy (combined ifosfamide, etoposide, and epirubicin [IEV]) followed by ASCT between September 2002 and September 2006 were included. All patients were evaluated by PET after 1 to 3 courses of IEV chemotherapy before ASCT, and all patients received a conditioning regimen of combined carmustine, etoposide, cytosine arabinoside, and melphalan. The prognostic impact of pretransplantation PET, sAA‐IPI score, histology, and previous response to first‐line chemotherapy was evaluated by univariate and multivariate analyses.

RESULTS.

Seventy‐two of 75 patients underwent ASCT. In a univariate analysis for progression‐free survival (PFS) and overall survival (OS), a significant association was observed with pretransplantation PET (PFS, P < .00001; OS, P < .01) and previous first‐line response (PFS, P = .02; OS, P = .04). In the multivariate framework, pretransplantation PET was identified as the only independent prognostic factor (PFS, P < .001; OS, P = .01).

CONCLUSIONS.

The current data indicated that pretransplantation PET is the main prognostic predictor in patients with aggressive B‐cell NHL who are scheduled for ASCT. Cancer 2008. © 2008 American Cancer Society.     

Lifetime alcohol intake and risk of non‐Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study

Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non‐Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10‐year periods from age 20 using recalled frequency and quantity of beverage‐specific consumption for 37,990 participants aged 40–69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow‐up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92–1.03; p value = 0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83–1.00; p value = 0.05), 1.03 (95% CI: 0.94–1.12; p value = 0.6), and 1.06 (95% CI: 0.83–1.37; p value = 0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low‐drinking cohort, we did not detect a dose‐dependent association between lifetime alcohol intake and NHL risk.     

Lifestyle factors,autoimmune disease and family history in prognosis of non‐hodgkin lymphoma overall and subtypes

Lifestyle factors and medical history are known to influence risk of non‐Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all‐cause and lymphoma‐related mortality was assessed in a population‐based cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma Etiology study in 1999–2002. Participants contributed time from NHL diagnosis until death or October 1, 2010, with virtually complete follow‐up through linkage to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using stratified and multivariable‐adjusted Cox regression models. During a median follow‐up of 8.8 years, 670 patients (44%) died, with the majority of deaths attributed to lymphoma (86%). Current versus never smoking at diagnosis was associated with increased rate of all‐cause death for all NHL (HR = 1.5, 1.2–1.8) and diffuse large B‐cell lymphoma (HR = 1.8, 1.2–2.7). Low educational level (HR = 1.3, 1.1–1.7, <9 vs. >12 years) and NHL risk‐associated autoimmune disease (HR = 1.4, 1.0–1.8) were associated with death for all NHL combined. However, evidence of an association with lymphoma‐related death was limited. Body mass index, recent sunbathing and family history of hematopoietic malignancy were not consistently associated with death after NHL or its specific subtypes. These results add to the evidence that cigarette smoking, socioeconomic status and certain autoimmune diseases affect survival after NHL. Further investigations are needed to determine how these factors should be incorporated into clinical prognostic assessment.     

Non‐Hodgkin lymphoma in Romania: a single‐centre experience

Epidemiologic studies of non‐Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the “Ion Chiricuta” Institute of Oncology in Cluj‐Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004–2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B‐cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T‐cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male‐to‐female ratio of 0.94. Patients with indolent B‐cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age‐standardized incidence rate/100 000 (ASR)—5.9; 95% CI 5.1–6.6] than in women (ASR—4.1; 95% CI 3.5–4.7) with age‐standardized male‐to‐female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B‐cell lymphoma (36%). The 5‐year, age‐standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006–2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.     

Surveillance imaging of Hodgkin lymphoma patients in first remission

BACKGROUND:

The majority of patients with Hodgkin lymphoma (HL) achieve disease remission after primary therapy. To the best of the authors' knowledge, no consensus exists for postremission surveillance imaging.

METHODS:

Retrospectively analyzed were 192 adult patients with classic HL in first remission. Events were defined as recurrent HL or secondary malignancies. Primary outcome was positive predictive value (PPV) of surveillance positron emission tomography/computed tomography (PET/CT) and CT scans in event detection. Secondary outcomes were costs and radiation exposures of surveillance scans.

RESULTS:

Sixteen events (12 recurrent HL cases and 4 secondary malignancies) were detected during a median follow‐up of 31 months. The PPV of surveillance PET/CT was 22.9% compared with 28.6% for CT (P = .73). Factors that were found to significantly improve the PPV of scans in detecting recurrent HL included PET and CT concordance, involvement of a prior disease site, or the occurrence of a radiographic abnormality within 12 months. There were too few events to determine whether event detection by PET/CT versus CT or the presence of symptoms at the time of event detection affected overall outcomes. The cost to detect a single event was approximately $100,000. Radiation exposure to detect a single event was 146.6 millisieverts per patient for each of 9 patients.

CONCLUSIONS:

For patients with HL in first disease remission, surveillance radiography appears to be expensive, with limited clinical impact. Surveillance CT is generally adequate. Cancer 2010. © 2010 American Cancer Society.     

Pharmacokinetic profile and first preliminary clinical evaluation of bendamustine in Taiwanese patients with heavily pretreated indolent B‐cell non‐Hodgkin lymphoma and mantle cell lymphoma

Prior studies found bendamustine is efficacious in patients with indolent B‐cell non‐Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B‐cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with indolent B‐cell NHL and five with MCL) to 90 or 120 mg/m² of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m² was given to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7 years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1–9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half‐life (t_1/2) of 0.67–0.8 h. Of the evaluable patients (n = 14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression‐free survival was 27.5 weeks. The most common grade 3–4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations. Copyright © 2014 John Wiley & Sons, Ltd.     

ABVD alone and a PET scan complete remission negates the need for radiologic surveillance in early‐stage,nonbulky Hodgkin lymphoma

BACKGROUND:

Patients with early‐stage, nonbulky classic Hodgkin lymphoma (cHL) undergo intensive posttreatment radiologic surveillance despite having a low risk of disease recurrence. The current study attempted to evaluate the risk of disease recurrence and the value of radiologic surveillance in patients treated with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment positron emission tomography (PET).

METHODS:

Forty‐seven patients who underwent therapy with interim and/or posttreatment PET scans were evaluated for disease recurrence during ≥ 24 months of follow‐up. Their presenting characteristics and imaging results were assessed and interpreted in relation to clinical outcome.

RESULTS:

All 47 patients were eligible for analysis. The majority of patients were female (35 patients) with a median age of 28 years (range, 17 years‐65 years.). The nodular sclerosing subtype was the predominant histology (41 patients). A total of 34 patients were staged with IIA disease, 6 with IA disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to Cotswolds modification of the Ann Arbor staging system). All patients completed 6 cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1 interim scan and 1 posttreatment scan); both were biopsy‐proven sarcoidosis. Two patients developed disease recurrence at 7 months and 24 months, respectively, after negative interim and posttreatment imaging. One case of recurrence was identified through surveillance imaging and the other was identified simultaneously by the patient and surveillance scan. A total of 45 patients experienced a durable CR; 21 had additional unscheduled imaging/workup during surveillance to investigate symptoms or imaging signs of concern.

CONCLUSIONS:

Because of a low risk of disease recurrence, posttreatment radiologic surveillance appears to be unnecessary in patients with early‐stage, nonbulky (CD20 negative) cHL who achieve a PET‐detected CR with the ABVD combination alone. This will reduce cumulative radiation exposure and health care costs in a predominantly young patient population. Cancer 2013. © 2012 American Cancer Society.     

Early serum TARC reduction predicts prognosis in advanced-stage Hodgkin lymphoma patients treated with a PET-adapted strategy

Among patients with advanced-stage classical Hodgkin lymphoma (cHL) receiving ABVD chemotherapy, PET performed after the first two treatment cycles (PET-2) has prognostic value. However, 15% of patients with a negative PET-2 will experience treatment failure. Here we prospectively evaluated serum thymus and activation-regulated chemokine (TARC) levels, to improve risk assessment in patients treated according to HD0607 PET-driven trial (#NCT00795613). In 266 patients with available serum samples, who have agreed to participate in a sub-study for assessment of the role of TARC monitoring, serum TARC levels were measured at baseline and at time of PET-2 by commercially available ELISA test kits. The primary end-point was to evaluate the association between TARC after 2 ABVD cycles and PFS. Median TARC-2 values were significantly higher in PET-2-positive patients compared to PET-2-negative patients (P = .001), and in patients with treatment failure compared to those in continuous CR (P = .01). The 4-year PFS significantly differed between patients with TARC-2 >800 pg/mL vs ≤800 pg/mL (64% vs 86%, P = .0001). Moreover, among PET-2-negative patients, elevated TARC-2 identified those with a worse prognosis (74% vs 89%; P = .01). In multivariable analysis, TARC-2 >800 pg/mL was a significant independent predictor of PFS in the whole study population (HR 2.39, P = .004) and among the PET-2-negative patients (HR 2.49, P = .02). In conclusion, our results indicate that TARC-2 serum levels above 800 pg/mL suggest the need for a stringent follow-up in PET-2-negative patients, and the evaluation of new drugs in PET-2-positive, who will likely fail to respond to intensification with escalated BEACOPP.     

GBV‐C/hepatitis G virus infection and non‐Hodgkin lymphoma: a case control study

We investigated whether there was an association between GBV‐C viremia and the development of non‐Hodgkin lymphoma (NHL) in 553 NHL cases and 438 controls from British Columbia, Canada. Cases were aged 20–79, diagnosed between March 2000 and February 2004, and resident in Greater Vancouver or Victoria. Cases and controls were tested for GBV‐C RNA by RT‐PCR and positive samples were genotyped. Overall, GBV‐C RNA was detected in 4.5% of NHL cases vs. 1.8% of controls [adjusted odds ratio (OR) = 2.72, 95% confidence interval (CI) = 1.22–6.69]. The association between GBV‐C RNA detection and NHL remained even after individuals with a history of prior transfusion, injection drug use and hepatitis C virus sero‐positivity were excluded. GBV‐C viremia showed the strongest association with diffuse large B cell lymphoma (adjusted OR = 5.18, 95% CI = 2.06–13.71). Genotyping was performed on 29/33 GBV‐C RNA positive individuals; genotypes 2a (n = 22); 2b (n = 5) and 3 (n = 2) were identified, consistent with the distribution of genotypes found in North America. This is the largest case‐control study to date associating GBV‐C viremia and NHL risk. As GBV‐C is known to be transmitted through blood products this may have important implications for blood safety.     

Classifying B‐cell non‐Hodgkin lymphoma by using MIB‐1 proliferative index in fine‐needle aspirates

BACKGROUND:

MIB‐1 proliferation index (PI) has proven helpful for diagnosis and prognosis in non‐Hodgkin lymphomas (NHLs). However, validated cutoff values for use in fine‐needle aspiration (FNA) samples are not available. We investigated MIB‐1 immunocytochemistry as an ancillary technique for stratifying NHL and attempted to establish PI cutpoints in cytologic samples.

METHODS:

B‐cell NHL FNA cases with available cytospins (CS) MIB‐1 immunocytochemistry results were included. Demographic, molecular, immunophenotyping and MIB‐1 PI data were collected from cytologic reports. Cases were subtyped according to the current World Health Organization classification and separated into indolent, aggressive, and highly aggressive groups. Statistical analysis was performed with pairwise Wilcoxon rank sum test and linear discriminant analysis to suggest appropriate PI cutpoints.

RESULTS:

Ninety‐one NHL cases were subdivided in 56 (61.5%) indolent, 30 (33%) aggressive, and 5 (5.5%) highly aggressive lymphomas. The 3 groups had significantly different MIB‐1 PIs from each other. Cutpoints were established for separating indolent (<38%), aggressive (≥38% to ≤80.1%) and highly aggressive (>80.1%). The groups were adequately predicted in 76 cases (83.5%) using the cutpoints and 15 cases showed discrepant PIs.

CONCLUSIONS:

MIB‐1 immunohistochemistry on CS can help to stratify B‐cell NHL and showed a significant increase in PI with tumor aggressiveness. Six misclassified cases had PIs close to the cutpoints. Discrepant MIB‐1 PIs were related to dilution of positive cells by non‐neoplastic lymphocytes and to the overlapping continuum of features between diffuse large B‐cell lymphoma and Burkitt lymphoma. Validation of our approach in an unrelated, prospective dataset is required. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.