Controversies on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma

Hodgkin lymphoma, even in advanced‐stage, is a highly curable malignancy, but treatment is associated with short‐term toxicity and long‐term side effects. Early predictive markers are required to identify those patients who do not require the full‐length standard therapy (and thus qualify for therapy de‐escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (FDG‐PET) after a few cycles of chemotherapy (also known as ‘interim FDG‐PET’) in predicting outcome in advanced‐stage Hodgkin lymphoma. Furthermore, multiple interim FDG‐PET‐adapted trials, in which patients with positive interim FDG‐PET scans are assigned to escalated therapies, and patients with negative interim FDG‐PET scans are assigned to de‐escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma in patients with positive and negative interim FDG‐PET findings following continuation of standard chemotherapy or escalated/de‐escalated therapy.     

Prognostic value of complete remission status at end‐of‐treatment FDG‐PET in R‐CHOP‐treated diffuse large B‐cell lymphoma: systematic review and meta‐analysis

This study systematically reviewed and meta‐analysed the prognostic value of complete remission status at end‐of‐treatment ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (FDG‐PET) in diffuse large B‐cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP). The systematic PubMed/MEDLINE search yielded seven suitable studies comprising a total of 737 R‐CHOP‐treated DLBCL patients who were in complete remission at end‐of‐treatment FDG‐PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end‐of‐treatment FDG‐PET ranged from 7·0% to 20·0%, with a weighted summary proportion of 13·7%. Five of seven studies reported progression‐free survival (PFS) of these patients at various specific time points, i.e., 2‐year PFS (n = 1), estimated 3‐year PFS (n = 3) and 5‐year PFS (n = 1), which was 83%, 85–86·4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3‐year OS (n = 2) and estimated 5‐year OS (n = 1), which were 90%, 93·6% and 83%, respectively. In conclusion, a non‐negligible proportion of R‐CHOP‐treated DLBCL patients who achieve complete remission according to end‐of‐treatment FDG‐PET experiences disease relapse during follow‐up.     

The role of FDG‐PET/CT in the evaluation of residual disease in paediatric non‐Hodgkin lymphoma

¹⁸F‐labelled–fluorodeoxyglucose positron emission tomography (FDG‐PET) findings are challenging to interpret for residual disease versus complete response in paediatric patients with non‐Hodgkin lymphoma (NHL). A biopsy is often warranted to confirm the presence or absence of viable tumour if there is clinical or radiographic evidence of residual disease. In this study, we compared conventional imaging and FDG‐PET/computerized tomography (CT) findings with biopsy results in 18 children with NHL. Our goal was to provide additional data to establish more reliable criteria for response evaluation. Residual disease was suspected after conventional imaging alone in eight patients, after FDG‐PET/CT alone in three and after both modalities in seven patients. Biopsy confirmed the presence of viable tumour in two patients. Two additional patients experienced progressive disease or relapse. The sensitivity and negative predictive value of FDG‐PET/CT using the London criteria to indicate residual tumour detectable by biopsy were 100%, but specificity was low (60%), as was the positive predictive value (25%). Thus, in this study, a negative FDG‐PET/CT finding was a good indicator of complete remission. However, because false‐positive FDG‐PET/CT findings are common, biopsy and close monitoring are required for accurate determination of residual disease in individual patients.     

Hodgkin lymphoma: a negative interim‐PET cannot circumvent the need for end‐of‐treatment‐PET evaluation

We examined the outcome of a cohort of patients with Hodgkin lymphoma (HL) in order to assess if fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) at the end of treatment (end‐PET) can be omitted when the interim PET (int‐PET) is negative. Seventy‐six ABVD(adriamycin, bleomycin, vinblastine, dacarbazine)‐treated patients were retrospectively included. No change in treatment was made on the basis of int‐PET results. Suspicious foci on end‐PET received biopsy confirmation whenever possible. Median follow‐up was 58·9 months. Uptake on int‐PET higher than liver (scores 4–5) was rated positive according to the Lugano classification, while a positive end‐PET corresponded to scores 3, 4 and 5. Fifteen patients had treatment failure. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy of int‐PET were 46·7%, 85·2%, 43·8%, 86·7% and 77·6%, respectively. For end‐PET the figures were: 80%, 93·4%, 75%, 95% and 90·8%. Eight patients with negative int‐PET had treatment failure; six of them were identified as non‐responders with end‐PET. The 5‐year progression‐free survival (PFS) was 87% for patients with negative int‐PET versus 56% with positive int‐PET. The 5‐year PFS was 96% with negative end‐PET versus 23% with positive end‐PET. The prognostic information from int‐PET as regards PFS (log‐rank test P = 0·0048) was lower than that provided by end‐PET (P < 0·0001). Int‐PET predicted only half of the failures. When used in clinical routine, a negative int‐PET study cannot obviate the need for end‐PET examination.     

Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre‐transplant FDG‐PET scan following salvage chemotherapy

The utility of ^[18F]fluoro‐2‐deoxy‐ d ‐glucose positron‐emission tomography (FDG‐PET) for predicting outcome after autologous stem cell transplantation (ASCT) for diffuse large B cell lymphoma (DLBCL) is uncertain – existing studies include a range of histological subtypes or have a limited duration of follow‐up. Thirty‐nine patients with primary‐refractory or relapsed DLBCL with pre‐ASCT PET scans were analysed. The median follow‐up was 3 years. The 3‐year progression‐free survival (PFS) for patients with positive PET scans pre‐ASCT was 35% vs. 81% for those who had negative PET scans (P = 0·003). The overall survival (OS) in these groups was 39% and 81% (P = 0·01), respectively. In a multivariate analysis, PET result, number of salvage cycles and the presence of relapsed or refractory disease were shown to predict a longer PFS; PET negativity (P = 0·04) was predictive of a longer OS. PET is useful for defining those with an excellent prognosis post‐ASCT. Although those with positive scans can still be salvaged with current treatments, PET may useful for selecting patients eligible for novel consolidation strategies after salvage therapies.     

Pre‐diagnosis cigarette smoking and overall survival in non‐Hodgkin lymphoma

We examined whether smoking prior to non‐Hodgkin lymphoma (NHL) diagnosis was associated with overall survival (OS) and conducted a meta‐analysis to assess the evidence relating pre‐diagnosis cigarette smoking with OS. Among 523 NHL patients, worse OS was suggested for greater pre‐diagnostic smoking habits when compared to never smokers. In the meta‐analysis (n = 5 patient populations), inferior OS was observed for greater number of cigarettes smoked per day, years of cigarette smoking, and pack‐years of cigarette smoking. The inferior survival was more pronounced for follicular than for diffuse large B cell lymphoma. Pre‐diagnosis cigarette smoking may adversely impact the survival of NHL patients.     

FDG‐PET/CT in the management of lymphomas: current status and future directions

FDG‐PET/CT is the current state‐of‐the‐art imaging in lymphoma and plays a central role in treatment decisions. At diagnosis, accurate staging is crucial for appropriate therapy selection: FDG‐PET/CT can identify areas of lymphoma missed by CT alone and avoid under‐treatment of patients with advanced disease stage who would have been misclassified as having limited stage disease by CT. Particularly in Hodgkin lymphoma, positive interim FDG‐PET/CT scans are adversely prognostic for clinical outcomes and can inform PET‐adapted treatment strategies, but such data are less consistent in diffuse large B‐cell lymphoma. The use of quantitative FDG‐PET/CT metrics using metabolic tumour volume, possibly in combination with other biomarkers, may better define prognostic subgroups and thus facilitate better treatment selection. After chemotherapy, FDG‐PET/CT response is predictive of outcome and may identify a subgroup who benefit from consolidative radiotherapy. Novel therapies, in particular immunotherapies, exhibit different response patterns than conventional chemotherapy, which has led to modified response criteria that take into account the risk of transient pseudo‐progression. In relapsed lymphoma, FDG‐PET/CT after second‐line therapy and prior to high‐dose therapy is also strongly associated with outcome and may be used to guide intensity of salvage therapy in relapsed Hodgkin lymphoma. Currently, FDG‐PET/CT has no role in the routine follow‐up after complete metabolic response to therapy, but it remains a powerful tool for excluding relapse if patients develop clinical features suggestive of disease relapse. In conclusion, FDG‐PET/CT plays major roles in the various phases of management of lymphoma and constitutes a step towards the pursuit of personalized treatment.     

Phase IA/II,multicentre, open‐label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non‐Hodgkin or Hodgkin lymphoma

Despite advancements in the treatment of non‐Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8‐week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa‐associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.     

Role of routine imaging in detecting recurrent lymphoma: A review of 258 patients with relapsed aggressive non‐Hodgkin and Hodgkin lymphoma

After first‐line therapy, patients with Hodgkin lymphoma (HL) and aggressive non‐HL are followed up closely for early signs of relapse. The current follow‐up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore, a retrospective multicenter study of relapsed HL and aggressive non‐HL (nodal T‐cell and diffuse large B‐cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002–2011 and relapsed after achieving complete remission on first‐line therapy. Characteristics and outcome of imaging‐detected relapses were compared with other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient‐reported symptoms alone or in combination with abnormal blood tests or physical examination in 64% of the patients. Routine imaging prompted relapse investigations in 27% of the patients. The estimated number of routine scans per relapse was 91–255 depending on the lymphoma subtype. Patients with imaging‐detected relapse had lower disease burden (P = 0.045) and reduced risk of death following relapse (hazard ratio = 0.62, P = 0.02 in multivariate analysis). Patient‐reported symptoms are still the most common factor for detecting lymphoma relapse and the high number of scans per relapse calls for improved criteria for use of surveillance imaging. However, imaging‐detected relapse was associated with lower disease burden and a possible survival advantage. The future role of routine surveillance imaging should be defined in a randomized trial. Am. J. Hematol. 89:575–580, 2014. © 2014 Wiley Periodicals, Inc.     

Bone marrow 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B‐cell lymphoma

This study aimed to investigate whether visual and quantitative ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography/computed tomography (FDG‐PET/CT)‐based bone marrow assessment can replace blind bone marrow biopsy (BMB) in newly diagnosed diffuse large B‐cell lymphoma (DLBCL). This retrospective study included 78 patients with newly diagnosed DLBCL who had undergone both FDG‐PET/CT and BMB. FDG‐PET/CT images were visually evaluated for bone marrow involvement. Patient‐based sensitivity of visual FDG‐PET/CT assessment was calculated using BMB as the reference standard. Metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, and 3D partial volume corrected mean metabolic volume product (cMVP_mean) of FDG‐avid bone marrow lesions were measured. Cox regression analysis was used to determine the influence of (potential) prognostic factors (BMB status, visual [dichotomous] FDG‐PET/CT bone marrow status, metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, 3D partial volume corrected mean metabolic volume product, and International Prognostic Index score) on progression‐free survival and overall survival. FDG‐PET/CT detected bone marrow involvement in 34 (43.6%) cases and BMB in 16 (20.5%) of 78 cases, of whom 11 were also detected by FDG‐PET/CT, resulting in a patient‐based sensitivity of 68.8% (95% confidence interval = 44.2%–86.1%) for FDG‐PET/CT. In the multivariate Cox proportional hazards model, only BMB status was an independent predictive factor of progression‐free survival (P = 0.016) and overall survival (P = 0.004). In conclusion, FDG‐PET/CT misses bone marrow involvement that has been detected by BMB in a non‐negligible proportion of patients. Furthermore, both visual and quantitative FDG‐PET/CT‐based bone marrow assessments are prognostically inferior to BMB. Therefore, FDG‐PET/CT cannot replace BMB in newly diagnosed DLBCL. Am. J. Hematol. 89:726–731, 2014. © 2014 Wiley Periodicals, Inc.     

F‐18 FDG‐PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem‐cell transplantation for relapsed and refractory Hodgkin lymphoma

Total lymphoid irradiation (TLI) followed by high‐dose chemotherapy and autologous haematopoietic stem cell transplant (aHSCT) is an effective strategy for patients with relapsed/refractory classical Hodgkin lymphoma (HL). We report outcomes for patients with relapsed/refractory HL who received TLI followed by high‐dose chemotherapy and aHSCT. Pre‐transplant fludeoxyglucose positron emission tomography (FDG‐PET) studies were scored on the 5‐point Deauville scale. Of 51 patients treated with TLI and aHSCT, 59% had primary refractory disease and 63% had active disease at aHSCT. The 10‐year progression‐free survival (PFS) and overall survival (OS) for all patients was 56% and 54%, respectively. Patients with complete response (CR) by PET prior to aHSCT had a 5‐year PFS and OS of 85% and 100% compared to 52% and 48% for those without CR (P = 0·09 and P = 0·007, respectively). TLI and aHSCT yields excellent disease control and long‐term survival rates for patients with relapsed/refractory HL, including those with high‐risk disease features. Achievement of CR with salvage therapy is a powerful predictor of outcome.     

Standardised uptake value of 18F‐FDG on staging PET/CT in newly diagnosed patients with different subtypes of non‐Hodgkin’s lymphoma

Objectives: Positron emission tomography using 2‐[fluorine‐18]‐fluoro‐2‐deoxy‐d ‐glucose (¹⁸F‐FDG) is considered to be the most beneficial imaging method for staging patients with non‐Hodgkin’s lymphoma (NHL). The intensity of ¹⁸F‐FDG accumulation may be determined by calculating the so‐called standardised uptake value (SUV). The study aimed at assessing the benefit of SUV_max determination in staging ¹⁸F‐FDG PET/CT in untreated patients with NHL. Methods: One hundred and forty‐nine initial staging ¹⁸F‐FDG PET/CT scans performed in patients with NHL between January 2007 and August 2009 were assessed, and the SUV_max was determined. Results: The highest mean and median values of SUV_max were observed in patients with diffuse large B‐cell lymphoma (DLBCL), the lowest mean and median values were found in small lymphocytic lymphoma. The overlap in SUV_max < 10 between DLBCL and the other subgroups of NHL was very significant. Statistically, no correlation was found between the lactate dehydrogenase and SUV_max values. On the other hand, a correlation of the Ki‐67 proliferative index of tumour cells and SUV_max was revealed (r = 0.409, P < 0.001). The geometric mean of SUV_max in patients with Ki‐67 ≤ 60 and those with Ki‐67 > 60 was 8.8 and 14.3, respectively (P < 0.001). Conclusions: The results confirm that SUV_max is not beneficial for making a more precise diagnosis in most patients with NHL. Correlation of SUV_max with the Ki‐67 values suggests that SUV_max might have a prognostic values in NHL.     

Long‐term outcomes,secondary malignancies and stem cell collection following bendamustine in patients with previously treated non‐Hodgkin lymphoma

Despite the long history of bendamustine as treatment for indolent non‐Hodgkin lymphoma, long‐term efficacy and toxicity data are minimal. We reviewed long‐term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39–84), and patients had received a median of 3 prior therapies. The histologies included grades 1–2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event‐free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow‐up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long‐term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient‐level, long‐term follow‐up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non‐Hodgkin lymphoma.     

Value of F-18 fluorodeoxyglucose positron emission tomography for predicting the clinical outcome of patients with aggressive lymphoma prior to and after autologous stem-cell transplantation

STUDY OBJECTIVES: To determine and compare the values of positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and CT for predicting clinical outcome of patients with aggressive lymphoma undergoing salvage cytoreductive chemotherapy followed by high-dose chemotherapy and autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Forty-three patients with lymphoma who underwent ASCT with FDG-PET evaluation were studied. Group 1 (n = 20) patients (6 patients with Hodgkin disease [HD], and 14 patients with non-Hodgkin lymphoma [NHL]) underwent PET 2 to 5 weeks after initiation of salvage chemotherapy, prior to ASCT. Group 2 (n = 23) patients (6 patients with HD, and 17 patients with NHL) underwent PET within a median interval of 2.4 months (range, 2 to 6 months) after ASCT. MEASUREMENTS AND RESULTS: Study end points were complete remission, relapse, or death. In group 1, 8 of 20 patients (40%) were disease free after a median follow-up of 13.3 months; 12 patients relapsed or died. PET findings were true-negative in 7 of 8 patients and true-positive in 11 of 12 patients who relapsed after ASCT. In group 2, 9 of 23 patients (39%) were disease free after a median follow-up of 16.5-months; 14 patients relapsed. PET findings were true-negative in 8 of 9 patients and true-positive in 13 of 14 patients who relapsed. Positive and negative predictive values of PET were 92% and 88% (group 1) and 93% and 89% (group 2), respectively. Predictive accuracy values of PET were 90% and 91% for group 1 and group 2, respectively, vs 58% and 67% for CT (p < 0.05). CONCLUSIONS: PET findings but not CT results were strongly correlated with disease-free survival (p < 0.01). Our results show that FDG-PET can be used to predict the post-ASCT outcome of lymphoma patients with high accuracy.     

The anti‐lymphoma activity of antiviral therapy in HCV‐associated B‐cell non‐Hodgkin lymphomas: a meta‐analysis

Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B‐cell non‐Hodgkin's lymphoma (B‐NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B‐NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV‐associated B‐NHL (HCV‐NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV‐NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV‐NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67–78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76–88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39–67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV‐associated marginal zone lymphomas (response rate 81%, 95%>CI, 74–87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61–79%, P = 0.07). In conclusion, in the current meta‐analysis, the overall response rate of HCV‐NHL under AVT justifies the recommendation for AVT as first‐line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis.     

Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open‐label studies

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B‐cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression‐free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non‐blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0–1, non‐bulky disease and non‐blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease.     

Association of personality with the development and persistence of obesity: a meta‐analysis based on individual–participant data

Personality is thought to affect obesity risk but before such information can be incorporated into prevention and intervention plans, robust and converging evidence concerning the most relevant personality traits is needed. We performed a meta‐analysis based on individual–participant data from nine cohort studies to examine whether broad‐level personality traits predict the development and persistence of obesity (n = 78,931 men and women; mean age 50 years). Personality was assessed using inventories of the Five‐Factor Model (extraversion, neuroticism, agreeableness, conscientiousness and openness to experience). High conscientiousness – reflecting high self‐control, orderliness and adherence to social norms – was associated with lower obesity risk across studies (pooled odds ratio [OR] = 0.84; 95% confidence interval [CI] = 0.80–0.88 per 1 standard deviation increment in conscientiousness). Over a mean follow‐up of 5.4 years, conscientiousness predicted lower obesity risk in initially non‐obese individuals (OR = 0.88, 95% CI = 0.85–0.92; n = 33,981) and was associated with greater likelihood of reversion to non‐obese among initially obese individuals (OR = 1.08, 95% CI = 1.01–1.14; n = 9,657). Other personality traits were not associated with obesity in the pooled analysis, and there was substantial heterogeneity in the associations between studies. The findings indicate that conscientiousness may be the only broad‐level personality trait of the Five‐Factor Model that is consistently associated with obesity across populations.     

Genetic polymorphisms in oxidative stress‐related genes are associated with outcomes following treatment for aggressive B‐cell non‐Hodgkin lymphoma

Variable survival outcomes are seen following treatment for aggressive non‐Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B‐cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress‐related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline‐based therapies. Their associations with progression‐free survival (PFS) and overall survival (OS) were estimated by Cox proportional hazard regression; associations with hematologic toxicity were estimated by logistic regression. To validate the findings, the top three SNPs were tested in an independent cohort of 572 DLBCL patients. The top SNPs associated with PFS in the discovery cohort were the rare homozygotes for MPO rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14–3.06, P = 0.013), AKR1C3 rs10508293 (HR = 2.09, 95% CI = 1.28–3.41, P = 0.0032) and NCF4 rs1883112 (HR = 0.66, 95% CI = 0.43–1.02, P = 0.06). The association of the NCF4 SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44–1.01, P = 0.05) and the meta‐analysis was significant (HR = 0.66, 95% CI = 0.49–0.89, P < 0.01). The association of the MPO SNP was attenuated in the validation dataset, while the meta‐analysis remained significant (HR = 1.64, 95% CI = 1.12–2.41). These two SNPs showed similar trends with OS in the meta‐analysis (for NCF4, HR = 0.72, 95% CI = 0.51–1.02, P = 0.07 and for MPO, HR = 2.06, 95% CI = 1.36–3.12, P < 0.01). In addition, patients with the rare homozygote of the NCF4 SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in NCF4 may contribute to treatment outcomes for patients with aggressive NHL. Am. J. Hematol. 89:639–645, 2014. © 2014 Wiley Periodicals, Inc.     

Phase II trial of zanolimumab (HuMax‐CD4) in relapsed or refractory non‐cutaneous peripheral T cell lymphoma

The efficacy and safety of zanolimumab (HuMax‐CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty‐one adult patients with relapsed or refractory CD4⁺ PTCL of non‐cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL‐not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single‐arm multi‐centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26–85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III–IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL‐NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor‐prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.     

Guideline for the laboratory diagnosis of functional iron deficiency

Patients with aggressive non‐Hodgkin lymphoma (NHL) who relapse after autologous stem cell transplantation (ASCT) have a poor prognosis. Additional therapy is often poorly tolerated, and new treatment modalities are needed. This efficacy and safety study was a retrospective analysis of two phase II trials (NHL‐002 and NHL‐003) that studied single‐agent lenalidomide in patients with relapsed/refractory aggressive NHL with prior (n = 87) compared with no prior ASCT (n = 179). The overall response rate in the ASCT group was 39% [14% complete response (CR)], including 29% in patients with diffuse large B‐cell lymphoma, 63% in mantle cell lymphoma, and 60% in transformed lymphoma. The timing of transplant relative to receiving lenalidomide had no effect on outcomes. Median progression‐free survival for the ASCT group was 3·7 months (16·9 months for patients in CR; 7·3 months for partial responders) at a median 12·5‐month follow‐up. Median response duration was 7·9 months. Regardless of prior ASCT, lenalidomide monotherapy was efficacious in heavily pretreated patients with aggressive, relapsed/refractory NHL, with a safety profile that was consistent with prior studies of single‐agent lenalidomide.