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Background Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome. Methods Forty-three newly diagnosed patients with lymphoma were included in the study; 24 with high-grade B-cell lymphoma (HGBCL) and 19 with classical Hodgkin lymphoma (cHL). Peripheral blood was prospectively collected and immune regulatory cells were identified by multi-color flow cytometry and analyzed in relation to healthy blood donors and clinical characteristics and outcome. Results The percentage of CD3-positive T-cells was lower ( p = 0.03) in the peripheral blood of lymphoma patients at diagnosis compared to healthy blood donors regardless of lymphoma subtype, although statistically, neither the percentage of monocytes ( p = 0.2) nor the T-cell/monocyte ratio ( p = 0.055) differed significantly. A significant decrease in the percentage of a subset of regulatory NK cells (CD7 + /CD3 − /CD56 bright /CD16 dim/− ) was identified in the peripheral blood of lymphoma patients compared to healthy blood donors ( p = 0.003). Lymphoma patients also had more granulocytic myeloid-derived suppressor cells (MDSCs) (p = 0.003) compared to healthy blood donors, whereas monocytic MDSCs did not differ significantly ( p = 0.07). A superior disease-free survival was observed for cHL patients who had an increase in the percentage of granulocytic MDSCs ( p = 0.04). Conclusions An altered profile of immune cells in the peripheral blood with a decrease in T-cells and regulatory NK-cells was observed in newly diagnosed lymphoma patients. CHL patients with higher percentages of regulatory NK cells and higher percentages of granulocytic MDSCs might have a better outcome, although the number of patients was low. Electronic supplementary material The online version of this article (10.1186/s12885-019-5529-0) contains supplementary material, which is available to authorized users.

IntroductionThe treatment of proximal hamstring avulsions is controversial. While several trials have investigated the outcome for patients treated surgically, there is today no prospective trial comparing operative treatment with non-operative treatment. This protocol describes the design for the proximal hamstring avulsion clinical trial (PHACT)—the first randomised controlled trial of operative versus non-operative treatment for proximal hamstring avulsions.Methods and analysisPHACT is a multicentre randomised controlled trial conducted across Sweden, Norway and Finland. Eligible patients (60 participants/treatment arm) with a proximal hamstring avulsion of at least two of three tendons will be randomised to either operative or non-operative treatment. Participants allocated to surgery will undergo reinsertion of the tendons with suture anchors. The rehabilitation programme will be the same for both treatment groups. When patient or surgeon equipoise for treatment alternatives cannot be reached and randomisation therefore is not possible, patients will be invited to participate in a parallel observational non-randomised cohort. The primary outcome will be the patient-reported outcome measure Perth hamstring assessment tool at 24 months. Secondary outcomes include the Lower Extremity Functional Score, physical performance and muscle strength tests, patient satisfaction and MR imaging. Data analysis will be blinded and intention-to-treat analysis will be preformed.Ethics and disseminationEthical approval has been granted by the Ethical Committee of Uppsala University (DNR: 2017–170) and by the Norwegian ethical board (REC: 2017/1911). The study will be conducted in agreement with the Helsinki declaration. The findings will be disseminated in peer-reviewed publications.Trial registration numberNCT03311997

View related articlesView Crossmark data Citing articles: 2 View citing articles differences in the metabolism of the two agents: zoledronic acid retains in the skeleton for years while denosumab does not incorporate in bone [8,12,16].Recently, a study on 1822 patients with bone metastases from multiple myeloma, breast cancer or prostate cancer compared zoledronic acid administered every three months to the standard monthly dosing. The less frequent dosing was shown to be non-inferior as the risk of SREs was similar during the three-monthly and monthly dosing of zoledronic acid. ONJ developed twice as often during the monthly as the three-monthly dosing [17]. Comprehensive data on the less intensive dosing of denosumab is lacking. REDUCE is a large phase III study currently recruiting prostate and breast cancer patients with bone metastases which randomizes patients to monthly or three-monthly dosing of denosumab.The risk of medication associated ONJ during bone-targeted therapies seems higher in clinical practice as compared to that reported in randomized trials. Our single institution case series found an 11.4% frequency of ONJ among prostate cancer patients. Only one third of the ONJ cases showed marked improvement whereas the rest caused chronic disability. ONJ is a common and often chronic complication of denosumab and zoledronic acid and more effective preventative measures are warranted. Disclosure statementLeena Vehmanen and Tapio Utriainen: scientific congress costs and lecture fees from pharmaceutical companies. Carl Blomqvist, Risto Kontio and Juho Suojanen: participation in an Amgen study project.