An atypical case of progressive multifocal leukoencephalopathy in a patient with high grade B-cell lymphoma causing diagnostic delay.

Progressive multifocal leukoencephalopathy (PML) is a rare disease of the central nervous system caused by opportunistic infection with JC virus. It presents in patients who are immunocompromised, and diagnosis is made by correlating clinical findings and radiological changes with the detection of JC virus in cerebrospinal fluid. Rarely, a brain biopsy is needed. A 72 year old with high grade B-cell lymphoma developed right arm weakness and limb ataxia shortly after his diagnosis. CNS involvement was excluded with a normal CT head, MRI brain/spine, and CSF examination. A paraneoplastic cause was suspected, and he received 5 cycles of Rituximab-containing chemotherapy to a complete metabolic remission. His neurology evolved during treatment despite serial MRI and CSF examination remaining normal. CSF and serum were both negative for JC virus by PCR. Following completion of chemotherapy, he deteriorated acutely with seizures and personality changes. It was only at this point that a repeat MRI showed new multiple scattered ring enhancing lesions within both cerebral hemispheres. The patient underwent a brain biopsy confirming JC virus positive-PML by immunohistochemistry and passed away one month later. This case illustrates the diagnostic challenges associated with PML and had several atypical features which led to diagnostic delay, specifically the onset of symptoms before starting immunochemotherapy, and the lack of radiological change despite evolving neurology. The eventual MRI abnormalities were not altogether classical for PML which, coupled with the JC-negativity in CSF and serum, meant a brain biopsy was required to reach the diagnosis.

Bendamustine plus rituximab for the treatment of Waldenström Macroglobulinemia: Patient outcomes and impact of bendamustine dosing.

Bendamustine and rituximab (BR) therapy is commonly used in the treatment of Waldenström Macroglobulinemia (WM). The impact dose of Bendamustine dose on response and survival outcomes is not well-established, and the impact of its use in different treatment settings is not clear. We aimed to report response rates and survival outcomes following BR, and clarify the impact of depth of response and bendamustine dose on survival. A total of 250 WM patients treated with BR in the frontline or relapsed settings were included in this multicenter, retrospective cohort analysis. Rates of partial response (PR) or better differed significantly between the frontline and relapsed cohorts (91.4% vs 73.9%, respectively; p < 0.001). Depth of response impacted survival outcomes: two-year predicted PFS rates after achieving CR/VGPR vs PR were 96% versus 82%, respectively (p = 0.002). Total bendamustine dose was predictive of PFS: in the frontline setting, PFS was superior in the group receiving ≥1000 mg/m2 compared with those receiving 800-999 mg/m2 (p = 0.04). In the relapsed cohort, those who received doses of <600 mg/m2 had poorer PFS outcomes compared with those who received ≥600 mg/m2 (p = 0.02). Attaining CR/VGPR following BR results in superior survival, and total bendamustine dose significantly impacts response and survival outcomes, in both frontline and relapsed settings.

Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-cell lymphoma: An observational study in Europe.

The rituximab biosimilar CT-P10 is approved for the treatment of non-Hodgkin lymphoma. Previous studies have demonstrated clinical similarity between CT-P10 and reference rituximab. However, real-world data relating to treatment in patients with DLBCL with rituximab biosimilars are limited. This study collected real-world data relating to the effectiveness and safety of CT-P10 treatment from the medical records of 389 patients with DLBCL (24 centers, five European countries). For the primary outcome (clinical effectiveness), overall survival (OS), progression-free survival (PFS), and best response (BR) were assessed. The percentage (95% confidence interval [95% CI]) of patients alive at 12-, 18-, and 30 months postindex (initiation of CT-P10) was 86% (82.4%-89.4%), 81% (76.9%-84.9%), and 76% (71.2%-80.1%), respectively. The PFS rate (percent, [95% CI]) at 12-, 18-, and 30 months postindex was 78% (74.2%-82.5%), 72% (67.9%-76.9%), and 67% (61.9%-71.7%), respectively. Median OS/PFS was not reached. For 82% (n = 312) of patients, the BR to CT-P10 was a complete response. Adverse events were consistent with known effects of chemotherapy. This international, multicenter study provides real-world data on the safety and effectiveness profile of CT-P10 for DLBCL treatment and supports the adoption of CT-P10 for the treatment of DLBCL.

The burden of diabetes-related foot disease among older adults in Australia.

Diabetes-related foot disease (DFD) is imposing an enormous burden on the health system and society due to the rapid growth of diabetes worldwide. Given the paucity of robust data on the disease burden of DFD in Australia, this study aimed to estimate the burden of disease due to DFD. The burden of DFD was estimated using the disability-adjusted life-years (DALY) approach. Data of 27 931 individuals aged 45 years and older with diabetes residing in New South Wales (NSW) from the 45 and Up Study survey were used in this study by linking it with the emergency department, hospital admissions and the deaths' registry data. The disease burden of DFD was estimated as 8915 DALY in NSW and 27 164 DALY in Australia in 2011. The burden was prominent among males and people aged 65 years and older. Most of the DALY (87%) was attributed to years of life lost or the fatal burden due to diabetes-related lower limb amputation (DRLEA). The total monetary values of DALY of DFD for NSW and Australia were estimated at approximately AUD 2 billion and AUD 6 billion annually, respectively. Preventative and curative priorities should be given to DRLEA to reduce this burden and target males, especially those aged 65 years and older.

Is Real-Time Ultrasound Reliably Able to Determine Kager's Fat Pad Motion during Walking?

The distal calcaneal wedge of the Kager's fat pad (KFP) has the mechanical role of lubricating the region between the Achilles tendon and calcaneus during ankle movements. The purpose of this study was to determine the reliability of real-time ultrasound (RTUS) in visualizing the motion of the KFP during walking in adults. Recordings obtained using RTUS (13-MHz linear array transducer, IOE 323, MyLab 70, Esoate, Genoa, Italy) of the Achilles enthesis region (N = 52) of 47 participants (ranging from 21-79 years in age) while walking on a motorised treadmill at their preferred speed were analysed by three blinded assessors. Motion of the KFP was rated on a 4-point Likert scale (normal to absent). There was good agreement (κ [95% confidence interval] = 0.646 [0.643-0.649]) among the three examiners, with very good agreement (0.823 [0.818-0.828]) when classifying the motion as normal. There was a poor correlation between the motion of the calcaneal wedge and participants' age (0.23-0.32). RTUS provides an adjunct to routine clinical examination to determine if there is normal motion of the calcaneal wedge during walking. This may be of benefit in patients with posterior heel pain for whom abnormal KFP motion is implicated.

Social determinants of diabetes-related foot disease among older adults in New South Wales, Australia: evidence from a population-based study.

BACKGROUND: Diabetes-related foot is the largest burden to the health sector compared to other diabetes-related complications in Australia, including New South Wales (NSW). Understanding of social determinants of diabetes-related foot disease has not been definitive in Australian studies. This study aimed to investigate the social determinants of diabetes-related foot disease in NSW. METHODOLOGY: The first wave of the 45 and Up Study survey data was linked with NSW Admitted Patient Data Collection, Emergency Department Data Collection, and Pharmaceutical Benefits Scheme data resulting in 28,210 individuals with diabetes aged 45 years and older in NSW, Australia. Three outcome variables were used: diabetes-related foot disease (DFD), diabetic foot ulcer (DFU), and diabetic foot infection (DFI). They were classified as binary, and survey logistic regression was used to determine the association between each outcome measure and associated factors after adjusting for sampling weights. RESULTS: The prevalence of DFD, DFU and DFI were 10.8%, 5.4% and 5.2%, respectively, among people with diabetes. Multivariate analyses revealed that the common factors associated with DFD, DFU and DFI were older age (75 years or more), male, single status, background in English speaking countries, and coming from lower-income households (less than AUD 20,000 per year). Furthermore, common lifestyle and health factors associated with DFD, DFU, and DFI were low physical activity (< 150 min of moderate-to-vigorous physical activity per week), history of diabetes for over 15 years, and having cardiovascular disease. CONCLUSION: Our study showed that about 1 in 10 adults with diabetes aged 45 years and older in NSW reported DFD. Interventions, including the provision of related health services aimed at reducing all forms of DFD in NSW, are recommended to target older individuals with a long history of diabetes, and coming from lower-income households.

Prevalence and Burden of Diabetes-Related Foot Disease in New South Wales, Australia: Evidence from the 45 and Up Study Survey Data Linked with Health Services Data.

Diabetes-related foot disease (DFD) is a major public health concern due to the higher risks of hospitalisation. However, estimates of the prevalence of DFD in the general population are not available in Australia. This study aims to estimate the prevalence of DFD and diabetes-related lower-extremity amputation (DLEA) among people aged 45 years and over in New South Wales (NSW), Australia. The NSW 45 and Up Study baseline survey data of 267,086 persons aged 45 years and over, linked with health services' administrative data from 2006 to 2012 were used in our study. Of these, 28,210 individuals had been diagnosed with diabetes, and our study identified 3035 individuals with DFD. The prevalence of DFD, diabetic foot ulcer (DFU), diabetic foot infection (DFI), diabetic gangrene (DG), and DLEA were 10.8% (95%CI: 10.3, 11.2), 5.4% (95% CI: 5.1, 5.8), 5.2% (95%CI: 4.9, 5.5), 0.4% (95%CI: 0.3, 0.5), and 0.9% (95%CI: 0.7, 1.0), respectively. DFD, DFU, DFI, DG, and DLEA were the most common among those who were older, born in Australia, from low-income households (

Comparison of EMG signal of the flexor hallucis longus recorded using surface and intramuscular electrodes during walking.

The purpose of this study was to compare the use of intramuscular (iEMG) and surface (sEMG) electromyography electrodes to record flexor hallucis longus (FHL) muscle activity during walking, and describe the role of the FHL. Muscle activity was recorded in 12 participants using sEMG and iEMG during treadmill and overground walking. Inter-tester reliability for visual detection of onset and offset of muscle activity was high (ICC = 1.00). During the loading period, the number of bursts of muscle activity was statistically significantly greater using iEMG compared to sEMG when treadmill walking (p = 0.016), and the duration of muscle activity was significantly greater for iEMG (p = 0.01) on both walking surfaces. There were no differences for peak and mean root mean squared (p ≥ 0.07). The FHL activity observed during the loading period (heel strike to forefoot strike) supports the function of the FHL to act as a dynamic ankle stabiliser of the rearfoot, as well as contributing to propulsion during the latter part of stance. The choice of electrodes to detect FHL activity should be dependent on whether the loading and propulsive periods are of interest, and whether treadmill or overground walking will be examined.

Non-pharmacological interventions and corticosteroid injections for the management of the Achilles tendon in inflammatory arthritis: a systematic review.

BACKGROUND: Achilles tendon (AT) pathologies, particularly Achilles enthesitis, are common in inflammatory arthritis (IA). Although there are various non-pharmacological interventions and injection therapies available, it is unknown if these interventions are effective for people with IA, as this population is often excluded from studies investigating the management of AT pathologies. This study aimed to identify and critically appraise the evidence for non-pharmacological interventions and corticosteroid injections in the management of AT pathology in those with IA. METHODS: All studies which met the inclusion criteria (AT interventions in adults with a working clinical diagnosis of IA, English language) were identified from the following databases: Medline, Embase, CINAHL and the Cochrane Library. The search strategies used the search terms 'spondyloarthropathies', 'inflammatory arthritis', 'achilles tendon', 'physical therapy', 'conservative management', 'injections', and related synonyms. Studies included were quantitative longitudinal design, such as randomised controlled trials, pseudo randomised and non-randomised experimental studies, observational studies, cohort studies, and case control studies. All outcome measures were investigated, quality assessment to determine internal and external validity of included studies was undertaken, and qualitative data synthesis was conducted. RESULTS: Of the 10,911 articles identified in the search strategy, only two studies that investigated the efficacy of corticosteroid injections for the management of the AT in IA met the inclusion criteria, and no studies were identified for non-pharmacological interventions. Both injection studies had low quality rating for internal and external validity, and thus overall validity. The included studies only investigated two outcome domains: pain and ultrasound (US) (B Mode and Doppler) identified abnormalities and vascularity in the AT. There is weak evidence suggesting a short-term improvement (6-12 weeks) in pain and for the reduction in some abnormal US (B-Mode and Doppler) detectable features (entheseal thickness, bursitis, and entheseal vascularity) at the AT and surrounding structures post-corticosteroid injection. CONCLUSION: Weak evidence is available regarding the efficacy of corticosteroid injections in reducing pain and inconclusive evidence for the improvement of abnormal US detectable features. No studies were identified for non-pharmacological interventions. It is evident from the lack of relevant literature that there is an urgent need for more studies assessing non-pharmacological interventions for the AT in people with IA.

Prognostic indices in diffuse large B-cell lymphoma in the rituximab era: an analysis of the UK National Cancer Research Institute R-CHOP 14 versus 21 phase 3 trial.

We compared the International Prognostic Index (IPI), Revised (R)-IPI and age-adjusted (aa)-IPI as prognostic indices for patients with diffuse large B-cell lymphoma (DLBCL) in the UK National Cancer Research Institute (NCRI) R-CHOP 14 versus 21 trial (N = 1080). The R-IPI and aa-IPI showed no marked improvement compared to the IPI for overall and progression-free survival, in terms of model fit or discrimination. Similar results were observed in exploratory analyses incorporating the Grupo Español de Linfomas/Transplante de Médula Ósea (GELTAMO)-IPI, where baseline ß2-microglobulin data were available (N = 655). Although our findings support current use of the IPI, a novel prognostic tool to better delineate a high-risk DLBCL group in the rituximab era is needed.

Linking the patient experience of foot involvement related to psoriatic arthritis to the International Classification of Functioning, Disability and Health.

OBJECTIVE: The aim was to categorize the patient experience of PsA-related foot involvement by linking it to the International Classification of Functioning, Disability and Health (ICF) framework. METHODS: Concepts, obtained from a previous qualitative investigation of people with PsA and health professionals into their perspective of PsA-related foot involvement, were linked to the full version of the ICF classification. Concepts were linked to the most appropriate ICF category using established linking rules, which enable a systematic and standardized linking process. All concepts were linked independently to the ICF by two investigators, followed by a third investigator for adjudication. The professional backgrounds of the investigators included occupational therapy and podiatry. RESULTS: More than 100 distinct ICF categories were linked to the interview concepts. The most represented ICF category was body functions (35%), followed by environmental factors (31%), activities and participation (19%) and body structure (15%). Concepts that could not be linked to the ICF were related to coping, aspects of time and knowledge. Health professionals identified a greater proportion of body functions and fewer activity and participation categories compared with patients, indicating a possible mismatch of key concerns. Interdisciplinary group analysis demonstrated merit. CONCLUSION: A list of ICF categories was generated, defining aspects of functioning important and relevant to the impact of PsA-related foot involvement. Despite the localized anatomical focus of this study, the effect of foot problems in PsA was linked to all components of the ICF, confirming the profound impact on functioning and daily life.

Development of a national survey on foot involvement among people with psoriatic arthritis in Australia using a best practice approach: a survey development protocol.

BACKGROUND: Limited research to date has defined the nature and extent of foot involvement in a psoriatic arthritis-specific population in Australia and the scale of the problem remains unclear. Survey research provides the ideal opportunity to sample a large population over a wide geographical area. Although quality criteria for survey research have been developed, research shows that adherence is low and that survey studies are poorly reported in peer-reviewed survey articles, which limits the ability to inform future survey design. The objective of this paper was to develop a national survey about foot involvement in people with psoriatic arthritis using a best practice approach. This is a methods paper for the development of survey research. METHODS: A systematic, multi-stage process of survey development was undertaken, which comprised 3 phases: 1) the generation of the conceptual framework and survey content; 2) the development of the survey and pre-testing and 3) development of the survey dissemination strategy. A survey best practice approach was adopted using iterative pre-testing techniques, which included; cognitive debriefing, cultural sensitivity review, survey design expert validation, subject expert validation and pilot testing. Targeted postal and online survey dissemination strategies were developed a priori to optimise the response rates anticipated. RESULTS: A 59-item survey with 8 sections was developed. Findings demonstrated a high survey response (n = 649), high data completeness (83% of respondents reached the end of the survey) and low rates of missing data (below 5% for 95% of respondents). Extensive survey pre-testing among the target population, health professionals and experts improved the overall quality, content validity, functioning and representativeness of the survey instrument, which optimised potential response rates. Clear audit trails that mapped the analytical process at each stage substantiated the rigour of the survey development methods. Robust strategies for sampling, survey dissemination and community engagement were deemed to have made a powerful contribution to response rates and the scale of information collected. CONCLUSIONS: Robust patient-centred methods in survey design were used to create a novel, high-quality survey to comprehensively evaluate psoriatic arthritis-related foot involvement. Transparent and precise description of the survey design and dissemination methods provides useful information to other researchers embarking on survey design in healthcare.

Point of care ultrasound imaging as a wound assessment tool in diabetic foot ulcers: a case series.

Foot ulceration is a common and devastating complication of diabetes. Traditionally, diabetic foot ulcers (DFU) are managed by multidisciplinary teams in tertiary hospital settings. Wound management decisions are based largely on visual observations at the point of care, using rudimentary evaluation of superficial tissues, such as wound tracings and photography combined with expert knowledge of the treating practitioners. Imaging based methods of assessment, such as X-ray, magnetic resonance imaging, scintigraphy or computed tomography are able to more comprehensively categorise wounds and to determine whether re-epithelialised wounds are in fact healed. Ultrasound has been advocated by the World Health Organization for the monitoring of chronic diseases and for screening because it is considered low risk, comfortable for patients and low cost. It can be performed in real time at the point of care and using B-mode, Doppler and elastography has the potential to provide clinically meaningful information for monitoring the status of hard-to-heal wounds, but to date this imaging technique has not been exploited in this field. This case series highlights the utility of diagnostic musculoskeletal ultrasound as an adjunct to traditional wound assessment that can provide diagnostically meaningful information to assist in clinical decision making. Future research will be needed to determine if routine incorporation of ultrasound in wound assessment improves patient outcomes.

Linking the effect of psoriatic arthritis-related foot involvement to the Leeds Foot Impact Scale using the International Classification for Functioning, Disability and Health: a study to assess content validity.

BACKGROUND: Previous research to describe the impact of foot involvement in psoriatic arthritis has used the Leeds Foot Impact Scale in Rheumatoid Arthritis (LFIS-RA) in the current absence of any psoriatic arthritis foot-specific tools. However, the LFIS-RA is a rheumatoid arthritis disease-specific outcome measure and its content validity for evaluating the experiences of people with psoriatic arthritis-related foot involvement is unknown. The study objective was to determine the content validity of the LFIS-RA for assessing people with psoriatic arthritis, using the International Classification of Functioning, Disability and Health (ICF) as the frame of reference. METHOD: Concepts within each item of the LFIS-RA were linked to the best-matched ICF categories using established linking rules, which enable a systematic and standardised linking process. All concepts were independently linked to the ICF by 2 investigators with different professional backgrounds, which included occupational therapy and podiatry. The list of ICF categories derived from previous research that pertained to the foot in psoriatic arthritis was then compared with the ICF categories linked to the LFIS-RA. The comparison was undertaken in order to determine the extent to which concepts important and relevant to people with psoriatic arthritis-related foot involvement were addressed. RESULTS: Thirty-five distinct ICF categories were linked to the LFIS-RA, which related to body functions (44%), activities and participation (35%), environmental factors (16%) and body structure (5%). In comparison with the ICF categories derived from concepts of the foot in psoriatic arthritis previously defined, the LFIS-RA provided coverage of key constructs including pain, functioning, daily activities, footwear restrictions and psychological impact. Other concepts of importance in psoriatic arthritis such as skin and toenail involvement, self-management and paid employment were not addressed in the LFIS-RA. CONCLUSION: Content validity of the LFIS-RA to determine the impact of foot functional impairments and disability in people with psoriatic arthritis was not supported by the results of this study. Future work should consider the development of a psoriatic arthritis foot-specific patient reported outcome measure, using the LFIS-RA as an important foundation.

The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival.

We present a long-term follow-up of the UK chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced, symptomatic follicular lymphoma (FL). This trial was the first to prospectively assess molecular response and the impact on outcomes for 400 patients. The median progression-free survival (PFS) and overall survival (OS) for CMD were 3·6 and 14·6 years vs. 3·0 and 15·7 years for FMD, respectively. Estimates for Restricted Mean Survival Time (RMST) suggested no difference in PFS or OS. For the whole cohort there was a highly significant difference in survival by POD24, with a median OS from a risk-defining event of 3·9 years compared to 13·7 years for all others (RMST P < 0·001). Molecular remission was achieved in 25/46 patients (54·3%) in the CMD arm and 20/41 (48·8%) in the FMD arm (P = 0·6). Molecular negativity resulted in median PFS of 5·6 years vs. 2·3 years for molecularly positive (log-rank P < 0·001) and median OS not reached versus 12·5 years (log-rank P < 0·01). No cases of progression occurred in minimal residual disease (MRD) negative patients after six years of follow-up. Although there was no difference in outcomes between arms, this is the first prospective study to report MRD negativity resulting in significantly improved OS.

Health professional views on the assessment and management of foot problems in people with psoriatic arthritis in Australia and New Zealand: a qualitative investigation.

BACKGROUND: Active foot disease persists in a high proportion of people with psoriatic arthritis despite the availability of pharmacological and non-pharmacological interventions to modify the course of the disease. Limited information exists on the provision of health care for foot disease in psoriatic arthritis. The objective of this study was to explore the views of health professionals on the assessment and management of people with psoriatic arthritis-related foot involvement. METHODS: Convenience sampling was used to recruit health professionals working in rheumatology outpatient clinics in Sydney, Australia and Auckland, New Zealand. Three focus groups were undertaken to explore the views and experiences of health professionals on the assessment and management of foot problems in people with psoriatic arthritis. All interviews were audio-recorded and transcribed verbatim. Qualitative data was analysed using a constant comparative analytic approach to identify themes. RESULTS: A total of seventeen health professionals participated including rheumatologists, podiatrists and a physiotherapist. Key themes derived from the focus groups suggest that health professionals perceived that people with psoriatic arthritis-related foot problems experience suboptimal management from symptom onset, to diagnosis and treatment. Frustration was expressed throughout discussions relating to lack of appropriate training and expertise required for the specialised management of foot problems typically encountered with psoriatic arthritis and poor access for patients to specialist podiatry services. CONCLUSIONS: This study provides new insight into the perspectives of health professionals on the management of foot problems related to psoriatic arthritis. Deficiencies in the diagnosis, assessment and treatment of foot problems were revealed. To meet the foot health needs of people with psoriatic arthritis, reducing diagnostic delay, improving knowledge and awareness about the disease among people with psoriatic arthritis and health professionals, and increasing specialist podiatry service provision may be required.

Perspectives of patients and health professionals on the experience of living with psoriatic arthritis-related foot problems: a qualitative investigation.

OBJECTIVE: The aim of the study was to explore how foot problems impact on the lives of people with psoriatic arthritis by interviewing patients and health professionals. METHOD: Participants were recruited from outpatient rheumatology clinics in Sydney, Australia, and in Auckland, New Zealand, using a convenience sampling strategy. People with psoriatic arthritis were asked questions in semi-structured interviews about their foot problems and the impact they have on daily living until qualitative data saturation. Focus groups were undertaken with health professionals to explore their understanding of the patient experience of psoriatic arthritis-related foot problems. All interviews were audio-recorded and transcribed verbatim. Constant comparative analysis was used to identify emerging themes from the data. RESULTS: Twenty-one people with psoriatic arthritis-related foot problems and 17 health professionals participated. Three overarching key themes were derived from patients and health professionals: (1) structural and functional foot manifestations, (2) impact on daily life leading to social withdrawal and reduced work productivity and (3) mediating factors influencing the severity of impact from foot problems on their lives such as social support, self-management strategies and experiences of health care. CONCLUSION: Foot problems caused functional disability and altered self-concept, which lead to a cascade of social, economic and psychological consequences. People with foot problems contend with profound disruption to their functioning and life roles. Whilst health professionals recognised the functional and visual impact that foot problems have on daily life, the emotional burden may be under-appreciated. Future work to determine the scale and types of foot problems in psoriatic arthritis is required.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.

BACKGROUND: Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients. METHODS: We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0-3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1-5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1-5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18). FINDINGS: Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6-38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21-1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections. INTERPRETATION: The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma. FUNDING: Bloodwise and the UK National Institute of Health Research.