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Purpose Sleep problems reported by hematological cancer patients are usually linked to higher levels of cancer-related fatigue. Although the awareness of sleep problems in solid cancer patients is rising, there has been less attention to the issue in hematological cancer patients. The present study assesses the differences in sleep by comparing physical activity and fatigue levels among hematological cancer patients during the onset of chemotherapy. Furthermore, it investigates the relationship between sleep, physical activity, and fatigue through mediation analysis. Methods The recruited sample consists of 58 newly diagnosed hematological cancer patients (47.1 �� 15.4 yrs; 51.7% males). Subjects completed questionnaires assessing sleep (PSQI), physical activity (visual analogue scale), fatigue (MFI-20), anxiety, depression (HADS), and quality of life (EORTC QLQ-C30) within two weeks from starting treatment. Results The sample reported more sleep problems in comparison to the German population norm. The classification as good (ca 25%) or bad sleepers (ca 75%) showed less frequent physical activity (p = .04), higher fatigue (p = .032), anxiety (p = .003), depression (p = .011) and pain (p = .011) in bad sleepers. The mediation analysis revealed significant indirect effects of sleep on fatigue through physical activity habits. Conclusions This study highlights the combined action of sleep problems and physical activity on fatigue during the onset of induction chemotherapy. These two parameters could represent meaningful intervention targets to improve a patient���s status during chemotherapy. Trial registration The study was registered on the WHO trial register (DRKS00007824)., Supportive care in cancer;Vol. 30. 2022, pp 167���176

Both, objective and self-perceived cognitive deficits, are frequently observed in patients with cancer before, during, and after medical treatment [1,2]. This phenomenon, also known as cancer-relat...

Purpose Physical activity promises to reduce disease-related symptoms and therapy-related side effects in patients suffering from aggressive lymphoma (L) or acute leukemia (AL). For an efficient training program, determination of patients’ physical capacity with a purposive exercise test is crucial. Here, we evaluated the feasibility and suitability of a graded exercise test (GXT) frequently applied in patients suffering from solid tumors by assessing whether patients achieved criteria for maximal exercise testing according to the American College of Sports Medicine (ACSM). Methods The GXT was performed by 51 patients with an aggressive L or AL prior to the start or in the earliest possible phase of high-dose chemotherapy, following a recommended protocol for cancer patients, starting at 20 Watts (W), with an increase of 10 W/min until volitional exhaustion. Subsequently, we investigated whether the following ACSM criteria were fulfilled: (1) failure of heart rate to increase despite increasing workload, (2) post-exercise capillary lactate concentration ≥ 8.0 mmol L−1, (3) rating of perceived exertion at exercise cessation > 17 on the 6–20 Borg Scale. Results Out of 51 patients, two, six, and 35 participants met the first, second, and third criterion, respectively. No relevant relationships between the completion of the criteria and patients’ characteristics (e.g., gender, age) were found. Conclusion Although results of this study suggest a general feasibility of the applied GXT, the ACSM criteria were not met by the majority of the participants. Therefore, this study raises doubts about the suitability of the GXT protocol and the ACSM criteria for this group of patients., Support Care Cancer

BackgroundCertified Cancer Centers must present all patients in multidisciplinary tumor boards (MTD), including standard cases with well-established treatment strategies. Too many standard cases can absorb much of the available time, which can be unfavorable for the discussion of complex cases. In any case, this leads to a high quantity, but not necessarily a high quality of tumor boardsObjectiveOur aim was to develop a partially algorithm-driven decision support system (DSS) for smart phones to provide evidence-based recommendations for first-line therapy of common urological cancers. To assure quality, we compared each single digital decision with recommendations of an experienced MTD and obtained the concordance.Design, setting and participants1873 prostate cancer patients presented in the MTD of the urological department of the University Hospital of Cologne from 2014 to 2018 have been evaluated.Outcome measurements and statistical analysisPatient characteristics included age, disease stage, Gleason Score, PSA and previous therapies. The questions addressed to MTD were again answered using DSS. All blinded pairs of answers were assessed for discrepancies by independent reviewers.Results and limitationsOverall concordance rate was 99.1% (1856/1873). Stage specific concordance rates were 97.4% (stage I), 99.2% (stage II), 100% (stage III), and 99.2% (stage IV.Quality of concordance were independent of age and risk profile.ConclusionsThe reliability of any DSS is the key feature before implementation in clinical routine. Although our system appears to provide this safety, we are now performing cross-validation with several clinics to further increase decision quality and avoid potential clinic bias.Patient summaryThe quality of therapeutic decisions provided in tumor boards is perhaps the most relevant criterion for optimal cancer outcome. This tool aims to provide optimal recommendations, to assess the quality on a case-by-case basis and furthermore to objectively display the quality of oncological care.Author summaryEveryday clinicians face the difficult task to choose the optimal treatment for their cancer patients due to the emergence of newly available therapeutics and continuously altering treatment guidelines. The resulting flood of information is impossible for clinicians to keep up with. Therefore, clinicians decide as a team, in so called tumor boards, upon the best possible cancer treatment for each patient. Even though the treatment decisions recommended by tumor boards play a critical role for the long-term survival of cancer patients, their accuracy in decision-making has hardly ever been assessed. Unfortunately, current digital tools that have been developed to support clinicians on the process of decision-making, have failed to provide treatment recommendations with sufficient accuracy. Therefore, we evaluated the quality of a novel decision-making application by comparing the decision concordance generated by the App with therapeutic recommendations given by a tumor board of a University Cancer Center. For newly diagnosed cancer patients we found that the novel tool matched the decisions made by the tumor board in almost 100% of the cases. These promising results not only show the potential providing digital support for patient care, but also provide objective quality management while saving board time in favor of discussing more complex cases.

Korperliche Aktivitat und gezielte sporttherapeutische Masnahmen haben sich mittlerweile als Supportivtherapie in der Onkologie bewahrt, um Nebenwirkungen der Erkrankung und der medizinischen Therapie zu reduzieren und die Lebensqualitat der Betroffenen zu steigern. Eine immer besser werdende epidemiologische Datenlage weist ferner darauf hin, dass korperliche Aktivitat und Sport das Erkrankungsrisiko reduzieren und die tumorspezifische Mortalitat beispielsweise fur Kolorektalkarzinome um bis zu 60 % senken. Diese Daten sind insbesondere im Vergleich zum relativ geringen Benefit einer adjuvanten Chemotherapie beachtlich und deuten auf den erheblichen immunologischen Effekt korperlicher Aktivitat hin. Einschrankend ist zu sagen, dass hierzu noch keine Daten groser prospektiv-randomisierter Interventionsstudien vorliegen, wobei sich die Durchfuhrung solcher Untersuchungen im Vergleich zu pharmakologischen Studien deutlich komplexer gestaltet. Um die Bewegungsempfehlungen jenseits der global empfohlenen 150 min moderater bis intensiver korperliche Aktivitat pro Woche zu konkretisieren, sind weitere, v. a. mechanistische Studien notwendig. Vor diesem Hintergrund soll dieser Artikel eine Ubersicht uber potenzielle biologische Mechanismen geben, uber die Bewegung und Sport der Entstehung und dem Fortschreiten von Tumorerkrankungen entgegenwirken konnen. Neben einer globalen Veranderung des systemischen Entzundungsgeschehens werden sportinduzierte Veranderungen von Immunzellfunktionen und direkte Effekte durch eine Veranderung des Tumormilieus diskutiert.

Zusammenfassung Hintergrund Umfassende Erkenntnisse zu bewegungstherapeutischen onkologischen Versorgungsstrukturen in Deutschland liegen zurzeit nicht vor. Ziel dieser Umfrage war eine Infrastruktur- und Angebotsanalyse der Bewegungsinterventionen an bundesdeutschen Krebszentren. Methoden 2015 wurden alle deutschen zertifizierten Krebszentren (N=756) mittels Fragebogen zu bestehenden bewegungstherapeutischen Angeboten befragt und mit definierten infrastrukturelle Mindestanforderung zur Umsetzung gezielter Bewegungstherapie verglichen. Ergebnisse 132 Krebszentren wurden in die Auswertung eingeschlossen. 90,9% der Zentren (N=120) bieten mindestens eine Form von Physio- oder Sporttherapie an. 22,7% der befragten Zentren erfüllen die infrastrukturellen Mindestanforderungen. Schlussfolgerungen Neueste wissenschaftliche Erkenntnisse im Zuge einer optimalen therapeutischen Trainingssteuerung und damit evidenzbasierten Versorgung scheinen zurzeit schwer umsetzbar, was die Etablierung einer Leitlinie zu onkologischer Sport- und Bewegungstherapie notwendig macht.

INTRODUCTION AND OBJECTIVE:As has been shown recently guideline-compliance is suboptimal concerning the management of testis cancer. Guideline incompliance results in significantly impaired long-te...

INTRODUCTION AND OBJECTIVE:Certified Cancer Centers are instructed to present 100% of all cases at multidisciplinary tumor boards (MTD). Discussion of standard cases limits the time of more demandi...

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically relevant side effect of chemotherapy. Approximately 50% of all leukemia, lymphoma, colorectal- and breast cancer patients are affected. CIPN is induced by neurotoxic chemotherapeutic agents and can manifest with sensory and/or motor deficits. It is associated with significant disability and poor recovery. Common symptoms include pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control and insecure gait. These symptoms not only affect activities of daily living, subsequently reducing patients’ quality of life, they have far more become a decisive limiting factor for medical therapy, causing treatment delays, dose reductions, or even discontinuation of therapy, which can affect the outcome and compromise survival. To date, CIPN cannot be prevented and its occurrence presents a diagnostic dilemma since approved and effective treatment options are lacking. Promising results have recently been achieved with exercise. We have revealed that sensorimotor training (SMT) or whole body vibration (WBV) can reduce the symptoms of CIPN and attenuate motor and sensory deficits. We furthermore detected a tendency that it may also have a preventive effect on the onset of CIPN. We are therefore conducting a prospective, multicentre, controlled clinical trial involving 236 oncological patients receiving either oxaliplatin (N = 118) or vinca-alkaloid (N = 118) who are randomized to one of two interventions (SMT or WBV) or a treatment as usual (TAU) group. Primary endpoint is the time to incidence of neurologically confirmed CIPN. Secondary endpoints are pain, maintenance of the functionality of sensory as well as motor nerve fibres as well as the level of physical activity. The baseline assessment is performed prior to the first cycle of chemotherapy. Subsequent follow-up assessments are conducted at 12 weeks, after completion of chemotherapy, and at a 3-month follow-up. Patients who develop CIPN receive an additional assessment at this time point, as it represents the primary endpoint. We hypothesize that SMT and WBV prevent the onset or delay the progression of CIPN, decrease the likelihood of dose reductions or discontinuation of cancer treatment and improve patients’ quality of life. Deutsche Register Klinischer Studien ( DRKS00006088 , registered 07.05.2014).

In patients with hematological malignancies, exercise is studied as a supportive measure with potential benefits on therapy and disease-related side effects. However, clinical trials have not yet integrated people with Down syndrome (DS), although this disability is associated with an increased risk for hematological malignancies. Therefore, we examined safety and feasibility of a mixed-modality exercise intervention in a male with DS undergoing high-dose chemotherapy for acute lymphoblastic leukemia. Furthermore, physical capacity and fatigue were assessed. Exercise sessions took place 3 times/wk over a 5-week period. Adherence to the exercise program was 100%, and no serious adverse events occurred. In contrast to the training sessions, applied endurance testing was not feasible. Furthermore, maintenance of fatigue level was observed. In conclusion, cancer patients with DS suffering from leukemia should not be excluded from physical activity or exercise programs.

BACKGROUND: Although people with haematological malignancies have to endure long phases of therapy and immobility, which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy. OBJECTIVES: In this update of the original review (published in 2014) our main objective was to re‐evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies considering the current state of knowledge. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 7) and MEDLINE (1950 to July 2018) trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing an aerobic physical exercise intervention, intending to improve the oxygen system, in addition to standard care with standard care only for adults suffering from haematological malignancies. We also included studies that evaluated aerobic exercise in addition to strength training. We excluded studies that investigated the effect of training programmes that were composed of yoga, tai chi chuan, qigong or similar types of exercise. We also excluded studies exploring the influence of strength training without additive aerobic exercise as well as studies assessing outcomes without any clinical impact. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events, mortality and 100‐day survival, standardised mean differences (SMD) for quality of life (QoL), fatigue, and physical performance, and mean differences (MD) for anthropometric measurements. MAIN RESULTS: In this update, nine trials could be added to the nine trials of the first version of the review, thus we included eighteen RCTs involving 1892 participants. Two of these studies (65 participants) did not provide data for our key outcomes (they analysed laboratory values only) and one study (40 patients) could not be included in the meta‐analyses, as results were presented as changes scores only and not as endpoint scores. One trial (17 patients) did not report standard errors and could also not be included in meta‐analyses. The overall potential risk of bias in the included trials is unclear, due to poor reporting. The majority of participants suffered from acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), malignant lymphoma and multiple myeloma, and eight trials randomised people receiving stem cell transplantation. Mostly, the exercise intervention consisted of various walking intervention programmes with different duration and intensity levels. Our primary endpoint overall survival (OS) was only reported in one of these studies. The study authors found no evidence for a difference between both arms (RR = 0.67; P = 0.112). Six trials (one trial with four arms, analysed as two sub‐studies) reported numbers of deceased participants during the course of the study or during the first 100 to 180 days. For the outcome mortality, there is no evidence for a difference between participants exercising and those in the control group (RR 1.10; 95% CI 0.79 to 1.52; P = 0.59; 1172 participants, low‐certainty evidence). For the following outcomes, higher numbers indicate better outcomes, with 1 being the best result for the standardised mean differences. Eight studies analysed the influence of exercise intervention on QoL. It remains unclear, whether physical exercise improves QoL (SMD 0.11; 95% CI ‐0.03 to 0.24; 1259 participants, low‐certainty evidence). There is also no evidence for a difference for the subscales physical functioning (SMD 0.15; 95% CI ‐0.01 to 0.32; 8 trials, 1329 participants, low‐certainty evidence) and anxiety (SMD 0.03; 95% CI ‐0.30 to 0.36; 6 trials, 445 participants, very low‐certainty evidence). Depression might slightly be improved by exercising (SMD 0.19; 95% CI 0.0 to 0.38; 6 trials, 445 participants, low‐certainty evidence). There is moderate‐certainty evidence that exercise probably improves fatigue (SMD 0.31; 95% CI 0.13 to 0.48; 9 trials, 826 patients). Six trials (435 participants) investigated serious adverse events. We are very uncertain, whether additional exercise leads to more serious adverse events (RR 1.39; 95% CI 0.94 to 2.06), based on very low‐certainty evidence. In addition, we are aware of four ongoing trials. However, none of these trials stated, how many patients they will recruit and when the studies will be completed, thus, potential influence of these trials for the current analyses remains unclear. AUTHORS' CONCLUSIONS: Eighteen, mostly small RCTs did not identify evidence for a difference in terms of mortality. Physical exercise added to standard care might improve fatigue and depression. Currently, there is inconclusive evidence regarding QoL, physical functioning, anxiety and SAEs . We need further trials with more participants and longer follow‐up periods to evaluate the effects of exercise intervention for people suffering from haematological malignancies. To enhance comparability of study data, development and implementation of core sets of measuring devices would be helpful.

Despite high rates of long-lasting remissions in patients with chronic lymphocytic leukaemia (CLL) treated with chemoimmunotherapy, none of the current therapeutic approaches is curative with the exception of allogeneic transplantation. One strategy to extend progression-free survival and long-term survival might be the establishment of consolidation therapies.In this trial, patients with complete or partial second remission after fludarabine-based treatment received consolidation therapy with alemtuzumab. The aim of this phase I/II trial was to determine the maximal tolerable dose (MTD) of alemtuzumab consolidation and to evaluate safety and efficacy in patients who responded to second-line fludarabine-based treatment. Thirteen patients in complete (CR) or partial remission (PR) received alemtuzumab dose escalation starting with 10 mg intravenously (iv) once weekly for 8 wk and increasing in 10-mg intervals per dose level.The main dose-limiting toxicities (DLTs) were infectious complications, and the MTD was determined at 10 mg. After alemtuzumab consolidation, seven of 13 patients (53%) were in CR, and four of these patients (30.7%) achieved minimal residual disease (MRD) negativity (

Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population.

The activating mutation of the BRAF serine/threonine protein kinase (BRAF V600E) is the key driver mutation in hairy cell leukemia (HCL), suggesting opportunities for therapeutic targeting. We analyzed the course of 21 HCL patients treated with vemurafenib outside of trials with individual dosing regimens (240-1920 mg/d; median treatment duration, 90 days). Vemurafenib treatment improved blood counts in all patients, with platelets, neutrophils, and hemoglobin recovering within 28, 43, and 55 days (median), respectively. Complete remission was achieved in 40% (6/15 of evaluable patients) and median event-free survival was 17 months. Response rate and kinetics of response were independent of vemurafenib dosing. Retreatment with vemurafenib led to similar response patterns (n = 6). Pharmacodynamic analysis of BRAF V600E downstream targets showed that vemurafenib (480 mg/d) completely abrogated extracellular signal-regulated kinase phosphorylation of hairy cells in vivo. Typical side effects also occurred at low dosing regimens. We observed the development of acute myeloid lymphoma (AML) subtype M6 in 1 patient, and the course suggested disease acceleration triggered by vemurafenib. The phosphatidylinositol 3-kinase hotspot mutation (E545K) was identified in the AML clone, providing a potential novel mechanism for paradoxical BRAF activation. These data provide proof of dependence of HCL on active BRAF signaling. We provide evidence that antitumor and side effects are observed with 480 mg vemurafenib, suggesting that dosing regimens in BRAF-driven cancers could warrant reassessment in trials with implications for cost of cancer care.

399 Background: Guideline-compliance in the management of GCT is suboptimal concerning and it results in significantly impaired long-term survival. To facilitating guideline concordant decisions even in less experienced MTD, we developed an algorithm-driven and validated mobile App to provide evidence-based recommendations. This App contains latest guideline versions and it is continuously updated to include practice changing clinical trials. It is the purpose of this study to analyse treatment decision made by MTD compared to guideline recommended therapy. Methods: 302 patients with GCT and MTD decision were randomly selected from our database. Concordance rates of MTD recommendations were compared to query results of the digital APP “Easy Oncology” performed by 2 independent, blinded reviewers. Descriptive statistics and data analysis included IBM´s statistics software SPSS Version 25. Correlation analysis of cancer case characteristics was performed by Kendalls Tau, Gamma, Pearson and Spearman tests. Results: Median age was 35 (18-82) years. Clinical stages I, IIA-C, and III were identified in 32%, 37%, and 31%, resp. According to IGCCCG 56%, 18%, and 25% demonstrated good, intermediate, and poor prognosis, resp. 56% were non-seminomas and 44% were seminomas. 60%, 16%, and 7% of MTD decisions were related to 1st-line, 2nd, and 3rd line therapy and 18% dealt with follow up. Overall concordance rate was 99% (301/302). Concordance rates in CS I, IIA-C, and III were 100%, 98% and 99%, resp. Concordance rates with regard to 1st, 2nd and 3rd line therapy were 99% (135/136), 100%, and 88% (13/14). Conclusions: Our validated expert-created mobile decision support system demonstrates easy and reliable application in daily routine in an expert tertiary referral centre. The APP relies on guideline and trial based information and avoids MTD decisions by expert opinions. It might improve the MTD decision in less experienced MTDs which is currently evaluated in a prospective study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically relevant side effect of chemotherapy. The symptoms diminish patients’ quality of life and represent a decisive limiting factor for medical therapy. To date, effective treatment options are lacking. Specific exercise interventions have proven promising to target relevant symptoms. We conducted a prospective, four-armed, randomized, controlled trial, to evaluate the effects of sensorimotor training (SMT) and whole-body vibration training (WBV) on patients with CIPN. Participants (N = 40) were randomized to either one of two intervention groups (SMT N = 10 or WBV N = 10) or oncological control group (N = 10) and matched by gender and age with a healthy control (N = 10). The intervention groups exercised twice a week for 6 weeks. Primary endpoint was the reduction of CIPN-related symptoms (improve peripheral deep sensitivity, Achilles tendon reflex (ASR) and patellar tendon reflex (PSR), light-touch perception, sense of position, and lower leg strength). Secondary endpoints were nerve conduction velocity and amplitude, balance control, quality of life, and CIPN-related pain. Patients exercising improved sensory and associated motor symptoms. Significant intergroup differences were found for the tendon reflexes (ASR P = .017 and PSR P = .020), peripheral deep sensitivity (P = .010), and pain (P = .043). Furthermore, tendencies were found regarding the subjective improvement of symptoms (P = .075) and two subscales of the EORTC-QLQ-C30 questionnaire: pain (P = .054) and dyspnea (P = .054). The results for the SMT group were superior regarding the tendon reflexes, and a tendency regarding the subjective report of symptoms, while WBV was superior regarding pain. SMT and WBV behold a large potential to reduce CIPN-related symptoms and can be considered feasible and safe for patients with CIPN (compliance 97.5%, no adverse events). Registration: DRKS00013027

Eine medizinisch-onkologische Therapie, aber auch die Krebserkrankung selbst verursacht zahlreiche akute wie auch chronische Nebenwirkungen. Vermehrt bestatigen Studien die validen Effekte von Bewegungstherapie zur bio-psycho-sozialen Regeneration. Doch fehlen in der onkologischen Versorgung bislang patientenorientierte Bewegungskonzepte, die die Translation wissenschaftlicher Erkenntnisse in die Therapie und Praxis ermoglichen. Reviews und RCT-Studien zu den Effekten von korperlicher Aktivitat auf krebsspezifische Defizite zeigen, dass spezifische Bewegungsprogramme einen positiven Einfluss auf Fatigue-Syndrom, Harninkontinenz, Lymphodem, Polyneuropathie, Arthralgie und den Nebenwirkungen einer Hormontherapie haben. Mit der zunehmend aussagekraftigeren Evidenz zur korperlichen Aktivitat in der Onkologie konnen im nachsten Schritt die aus den Studien resultierenden Empfehlungen in Praxis und Therapie ubertragen werden. Dazu wurde das personalisierte Behandlungskonzept „Onkologische Trainings- und Bewegungstherapie“ (OTT) entwickelt.

To evaluate the effect of first-line and subsequent therapies, the outcome of 1,558 patients with chronic lymphocytic leukemia from five prospective phase II/III trials conducted between 1999 and 2010 was analyzed. The 3-year overall survival rate was higher after first-line treatment with chemoimmunotherapies such as fludarabine/cyclophosphamide/rituximab (87.9%) or bendamustine/rituximab (90.7%) compared to chemotherapies without an antibody (fludarabine/cyclophosphamide: 84.6%; fludarabine: 77.5%; chlorambucil: 77.4%). Furthermore, the median overall survival was longer in patients receiving at least one antibody-containing regimen in any treatment line (94.4 months) compared to the survival in patients who never received an antibody (84.3 months, P24 months after first-line therapy repeated the first-line regimen. Among 315 patients requiring treatment ≤24 months after first-line therapy, cyclophosphamide/doxorubicin/vincristine/prednisone with or without rituximab as well as alemtuzumab were the most commonly used therapies. In these early relapsing patients, the median overall survival was shorter following therapies containing an anthracycline and/or three or more cytotoxic agents (e.g. cyclophosphamide/doxorubicin/vincristine/prednisone or fludarabine/cyclophosphamide/mitoxantrone, 30.0 months) compared to single agent chemotherapy (e.g. fludarabine; 39.6 months) and standard chemoimmunotherapy (e.g. fludarabine/cyclophosphamide/rituximab: 61.6 months). In conclusion, the analysis confirms the superior efficacy of chemoimmunotherapies in patients with chronic lymphocytic leukemia. Moreover, the use of aggressive chemo(immuno)therapy combinations in patients with an early relapse does not offer any benefit when compared to less intensive therapies. Trial identifier: NCT00281918, ISRCTN75653261, ISRCTN36294212, NCT00274989 and NCT00147901.

Bewegungstherapeutische Masnahmen sind mittlerweile integraler Bestandteil der onkologischen (Fruh-)Rehabilitation. Neben dem Ausdauer- und Koordinationstraining ist das Krafttraining ein essenzieller Bestandteil der Bewegungstherapie, um beispielsweise den Nebenwirkungen eines Lymphodems, einer Antiandrogentherapie oder einer Kachexie entgegenzuwirken. Um das Outcome von Bewegungsprogrammen vor dem Hintergrund von verschiedensten Nebenwirkungen von onkologischen Erkrankungen und deren Therapien zu optimieren, sind zwingend weitere Studien notwendig. In der vorliegenden Studie sollte untersucht werden, inwieweit ein intensives Krafttraining einem moderaten Krafttraining hinsichtlich des Kraftzuwachses uberlegen ist. Zu diesem Zweck wurden 31 Tumorpatienten ohne Krafttrainingserfahrung (unterschiedlichster Entitaten und Therapiestatus) in eine moderate Trainingsgruppe (MT, n=17) und eine Hypertrophietrainingsgruppe randomisiert (HT, n=14). Alle Patienten trainierten zunachst uber 8 Wochen 2-mal wochentlich in einem Kraftausdauerzirkel (je 2 Durchgange), der 6 Kraftgerate (je 20 Wiederholungen [Wdh]) fur die grosen Muskelgruppen beinhaltete. In den folgenden 8 Wochen trainierte die MT weiter bei 20 Wdh, wohingegen fur die HT der Widerstand so erhoht wurde, dass lediglich 8–12 Wdh moglich waren. Die Maximalkraft der Patienten wurde vor Beginn der Intervention (t0), nach 8 Wochen (t1) und nach 16 Wochen (t2) mittels eines hypothetischen One-Repition-Maximum- (h1RM-)Tests erfasst. Die Ergebnisse zeigten bei ahnlichem Ausgangsniveau der beiden Gruppen einen signifikant erhohten Kraftzuwachs fur fast alle Muskelgruppen von t1 zu t2 in der HT. Der Mehrwert dieser Ergebnisse ist weniger die Feststellung, dass ein HT hinsichtlich des Kraftzuwachses einem MT uberlegen ist, sondern vielmehr, dass ein HT auch fur Tumorpatienten gut durchfuhrbar ist. Insofern keine Kontraindikationen bestehen, kann somit intensives Krafttraining v. a. fur den Muskelaufbau empfohlen werden. Ob der reine Kraftzuwachs fur Nebenwirkungen wie das Fatigue-Syndrom eine zentrale oder eher untergeordnete Rolle spielt, mussen weitere Untersuchungen zeigen.

In addition to clinical staging, a number of biomarkers predicting overall survival (OS) have been identified in chronic lymphocytic leukemia (CLL). The multiplicity of markers, limited information on their independent prognostic value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We therefore performed an analysis of 23 prognostic markers based on prospectively collected data from 1948 CLL patients participating in phase 3 trials of the German CLL Study Group to develop a comprehensive prognostic index. A multivariable Cox regression model identified 8 independent predictors of OS: sex, age, ECOG status, del(17p), del(11q), IGHV mutation status, serum β2-microglobulin, and serum thymidine kinase. Using a weighted grading system, a prognostic index was derived that separated 4 risk categories with 5-year OS ranging from 18.7% to 95.2% and having a C-statistic of 0.75. The index stratified OS within all analyzed subgroups, including all Rai/Binet stages. The validity of the index was externally confirmed in a series of 676 newly diagnosed CLL patients from Mayo Clinic. Using this multistep process including external validation, we developed a comprehensive prognostic index with high discriminatory power and prognostic significance on the individual patient level. The studies were registered as follows: CLL1 trial (NCT00262782, http://clinicaltrials.gov), CLL4 trial (ISRCTN 75653261, http://www.controlled-trials.com), and CLL8 trial (NCT00281918, http://clinicaltrials.gov).

To assess the effects of chemoimmunotherapy on post-chemotherapy cognitive impairments (PCCI) in patients with B-cell non-Hodgkin lymphoma (NHL), we used objective and subjective measures of cognitive functions in combination with serum parameters and neuroelectric recordings. Self-perceived status of cognition, fatigue and emotional functioning were reduced in patients (n=30) compared to healthy controls (n=10). Cognitive performance was impaired in patients with NHL compared to controls and a norm sample (n=1179). PCCI was more severe in patients treated with rituximab and bendamustine (BR) than in patients who received R in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) polychemotherapy (R-CHOP). Individual alpha peak frequency and serum brain-derived neurotrophic factor (BDNF) levels in patients with NHL correlated with accuracy in the objective cognition test. Higher serum interleukin-6 (IL-6) concentrations were associated with higher fatigue levels. Patients with NHL and especially those who were treated with BR were affected by PCCI. BDNF and IL-6 might be involved in the pathogenesis of PCCI and fatigue.

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically meaningful side effect of cancer treatment. CIPN is induced by neurotoxic agents, causing severe sensory and/or motor deficits, resulting in disability and poor recovery, reducing patients’ quality of life and limiting medical therapy. To date, effective treatment options are lacking. Whole-body vibration (WBV) training can attenuate motor and sensory deficits. We are conducting a two-armed, multicentre, assessor-blinded, randomised controlled trial, to investigate the effects of WBV on relevant symptoms of CIPN and determine the training characteristics.Methods and analysisIn this ongoing study, 44 patients who have completed therapy in the past 3 months, with a neurologically confirmed CIPN are assessed before and after a 12-week intervention and follow-up. The intervention group receives WBV twice a week. Exercises are individually tailored according to the initially determined optimal neuromuscular response. The control group receives care as usual.Primary endpoint is the patient reported reduction of CIPN-related symptoms (Functional Assessment of Cancer Therapy/Gynaecology Oncology Group—Neurotoxicity). Secondary endpoints are compound muscle action potentials, distal motor latency, conduction velocity, F-waves from the tibial and peroneal nerve, antidromic sensory nerve conduction studies of the sural nerve, normalised electromyographic activity, peripheral deep sensitivity, proprioception, balance, pain, the feasibility of training settings, quality of life and the level of physical activity.Aim, ethics and disseminationThe study was approved by both responsible ethics committees. (1) Our results may contribute to a better understanding of the effects of WBV on motor and sensory functions and (2) may provide information whether WBV at the most effective setting, is feasible for neuropathic patients. (3) Our results may also contribute to improve supportive care in oncology, thereby enhancing quality of life and enabling the optimal medical therapy. All results will be published in international peer-reviewed journals as well as a manual for clinical practice.Trial registration numberNCT03032718

High-dose chemotherapy followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed primary central nervous system lymphoma. In this retrospective multicenter study, we investigated prognosis and baseline risk factors in patients with primary central nervous system lymphoma who underwent this treatment approach. We retrospectively analyzed 105 immunocompetent patients with primary central nervous system lymphoma who underwent high-dose chemotherapy followed by autologous stem cell transplantation with or without whole brain radiotherapy as first-line consolidation treated at 12 German centers between 1997 and 2011. We estimated survival rates and investigated the impact of age, performance status, serum lactate dehydrogenase level, and deep brain involvement on overall and progression-free survival. Patients were additionally categorized into three prognostic groups according to the Memorial Sloan Kettering Cancer Center prognostic model. After a median follow up of 47 months, median progression-free survival and overall survival was reached after 85 and 121 months; 2- and 5-year survival rates were 82% and 79%, respectively. The Memorial Sloan Kettering Cancer Center prognostic model did not predict survival. Only age revealed some evidence of prognostic relevance. Overall response rate was 95%; of those patients with progressive disease before high-dose chemotherapy, 7 of 20 achieved ongoing complete remission after therapy without whole brain radiation therapy. Transplantation-associated mortality was 2.8%. High-dose chemotherapy followed by autologous stem cell transplantation is a highly effective and safe treatment modality for selected primary central nervous system lymphoma patients. Superiority compared to standard chemotherapy still warrants further investigation.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess and summarise the evidence for purine analogues plus cyclophosphamide compared with purine analogues alone for first‐line treatment of patients with CLL.

This systematic review analyzes current data on effects of exercise interventions and physical activity behavior on objective and subjective cancer related cognitive impairments (CRCI). Out of the 19 studies which met all inclusion criteria, five RCTs investigated rodents, whereas the other 14 trials explored humans and these included six RCTs, one controlled trial, two prospective noncontrolled trials, one case series, one observational study, and three cross-sectional studies. The results from animal models revealed positive effects of exercise during and after chemotherapy or radiation on structural alterations of the central nervous system, physiological as well as neuropsychological outcomes. The overall study quality in patient studies was poor. The current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs (e.g., Yoga) with benefits on self-perceived cognitive functions as well as a reduction of chronic inflammation for breast cancer patients in the aftercare. Exercise potentially contributes to the prevention and rehabilitation of CRCI. Additional RCTs with standardized neuropsychological assessments and controlling for potential confounders are needed to confirm and expand preliminary findings.

The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m(2) intravenously (i.v.) Day 1, ifosfamide 2 g/m(2) i.v. Days 3- 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m(2) i.v. Days 1-2, thiotepa 40 mg/m(2) i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m(2) i.v. Day -5, thiotepa 2×5 mg/kg i.v. Days -4 to -3 and etoposide 150 mg/m(2) i.v. Days -5 to -3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173).

Fludarabine and cyclophosphamide in combination with alemtuzumab in patients with primary high-risk, relapsed or refractory chronic lymphocytic leukemia

Phase 1b trial of atacicept, a recombinant protein binding BLyS and APRIL, in patients with chronic lymphocytic leukemia

Purpose The objective of this trial was to evaluate safety and efficacy of bendamustine combined with rituximab (BR) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL). Patients and Methods Seventy-eight patients, including 22 patients with fludarabine-refractory disease (28.2%) and 14 patients (17.9%) with deletion of 17p, received BR chemoimmunotherapy. Bendamustine was administered at a dose of 70 mg/m2 on days 1 and 2 combined with rituximab 375 mg/m2 on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses for up to six courses. Results On the basis of intent-to-treat analysis, the overall response rate was 59.0% (95% CI, 47.3% to 70.0%). Complete response, partial response, and nodular partial response were achieved in 9.0%, 47.4%, and 2.6% of patients, respectively. Overall response rate was 45.5% in fludarabine-refractory patients and 60.5% in fludarabine-sensitive patients. Among genetic subgroups, 92.3% of patients with del(11q), 100% with trisomy 12, 7.1% with del(17p), and 58.7% with unmutated IGHV status responded to treatment. After a median follow-up time of 24 months, the median event-free survival was 14.7 months. Severe infections occurred in 12.8% of patients. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were documented in 23.1%, 28.2%, and 16.6% of patients, respectively. Conclusion Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease. Major but tolerable toxicities were myelosuppression and infections. These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL.

An allogeneic hematopoietic stem cell transplantation (HSCT) can have profound and lasting adverse effects on a patient’s physical and psychological well-being. So far, only few studies have investigated the effectiveness of physical activity over the entire inpatient phase of an allogeneic HSCT. Purpose: We performed a randomized controlled study to examine the influence of a controlled moderate exercise program starting parallel to chemotherapeutic conditioning and total body irradiation on the patient’s physical and psychological constitution. Patients and methods: Forty-seven patients undergoing an allogeneic HSCT were randomly assigned to an exercise group (EG) or a control group (CG). While the EG took part in an endurance and activity of daily living-training twice a day, the CG received the clinic’s standard physiotherapy program once a day. Results: Significant differences and/or trends in favor of the EG were observed regarding the primary endpoint endurance performance (P = 0.002), muscular strength (P = 0.022), fatigue (P = 0.046), and emotional state (P = 0.028) without posing an additional risk for the individual. Conclusion: The results show that the training program is feasible and seems to have positive influences on physical performance and quality of life in patients undergoing an allogeneic HSCT. However, further studies are necessary to confirm these results.

Patients undergoing intensive chemotherapy for acute leukaemia or aggressive lymphoma not only suffer from the direct side effects of chemotherapy such as infections due to long-lasting immuno-suppression and aplasia, but also from marked fatigue and the inability to do normal physical activity. Furthermore, especially in patients with severe thrombocytopenia, anaemia and leukopenia, doctors recommend abstaining from physical exercise due to the risk of potential bleeding and tissue damage. The normally recommended cutoff level to perform exercise is 50,000 platelets per microliter or haemoglobin of 8 g/dl. This leads to a vicious cycle of loosing physical strength and muscles with subsequent development of treatment-related cachexia and an increased treatment mortality. As number of publications focus on the importance of physical exercise in patients with solid tumours, increasing evidence is found that suggests positive effects on major clinical endpoints such as rate of infection, quality of life and even relapse rate and overall survival. With this work, we intended to address whether intense supervised ergometer training is feasible in patients with severe pancytopenia and whether it has any effect on patients undergoing high-dose chemotherapy. Furthermore, this study was initiated as the groundwork for a large phase III randomised trial.

Infection is a significant cause of morbidity and death in patients with chronic lymphocytic leukemia (CLL). Increased infectious events may arise from the multiple courses of immunosuppressive therapy and progressive deterioration of a patient's immune system over the course of disease. The humanized, anti-CD52 monoclonal antibody alemtuzumab (Campath or Campath-1H) has shown notable activity for both untreated and fludarabine-refractory CLL. The antibody not only targets malignant cells but also affects normal, healthy immune cells. The cumulative effects of the malignancy and successive courses of treatments adversely impinge on a patient's defense response to certain bacterial, fungal, and viral infections. In this review article, we provide an overview of common infectious events associated with alemtuzumab therapy in CLL. We also discuss recommendations for effectively monitoring and managing infections in CLL patients.

The German Competence Network Malignant Lymphomas (KML) is an initiative of the German Federal Ministry of Education and Research with the goal of establishing a cooperative network between lymphoma study groups to support clinical lymphoma research. The network was initiated in 1999 and comprises 9 national lymphoma study groups. More than 8,600 patients are recruited every year into currently 55 clinical trials by more than 2,400 centers in Germany and Europe. It was the specific aim of the 1st international workshop of the KML (March 6 and 7, 2006) in Cologne to bring together international specialists in the field of lymphoma to discuss current concepts of lymphoma pathogenesis and treatment strategies. This report summarizes novel aspects of pathogenesis and targeted approaches, maintenance therapy, management of the elderly patients, and the use of positron emission tomography for clinical decision making.

Oncological treatments can lead to acute and chronic cancer related toxicities. In recent years, a large number of clinical studies have reported positive effects of exercise to the bio-psycho-social regeneration of cancer patients. However, very few evidence-based programs have been implemented into practice with little opportunity for cancer patients to engage in such programs. Reviews and RCT studies on exercise and cancer are showing that specific exercise programs have a positive impact on fatigue syndrome, urinary incontinence, lymphedema, polyneuropathy, arthralgia, and androgen deprivation related toxicities. With the increasing evidence for exercise oncology interventions, recommendations arising from clinical trials should be translated into clinical practice and this should be viewed as an important next step in this fast moving field of exercise oncology. For that the personalized treatment concept "Oncologic clinical exercise" (OTT) was developed.

The introduction of new therapeutic agents, such as fludarabine phosphate (Fludara) and alemtuzumab (MabCampath, Campath), has made it possible to treat B-cell chronic lymphocytic leukemia (B-CLL) more effectively, compared with alkylating agents. However, although an increasing number of patients are able to achieve complete remission (CR), relapse is almost inevitable, because of the re-emergence of the malignant clone from small numbers of residual malignant cells. This phenomenon has introduced a need for a more sensitive assessment of low-level disease which, in turn, has encouraged the development of therapies aimed at the eradication of all residual disease in CR patients. The eradication of residual disease is associated with improved remission durability and has great potential in offering the possibility of cure. Alemtuzumab is the foundation of many eradication-based treatment approaches because of its ability to achieve clinical remissions and to successfully purge minimal residual disease (MRD) from both blood and bone marrow in B-CLL patients. This article describes and compares polymerase chain reaction (PCR) and flow cytometric methodologies for the assessment of MRD, and presents data demonstrating that alemtuzumab can eliminate residual malignant cells from blood and bone marrow (whether assessed by PCR or flow cytometry) at the highest levels of sensitivity currently available. The ability to clear MRD from bone marrow in patients achieving clinical CR using alemtuzumab is a significant step forward in the treatment of B-CLL, and supports treatment strategies in which alemtuzumab is used in combination with other agents. Purging of MRD from both blood and bone marrow also enables patients to proceed to autologous hematopoietic stem cell transplantation, a strategy that is able to achieve long-term remission.

Beta blockers have been shown to prolong survival in chronic heart failure. It is currently a matter of debate whether any beta blocker is superior to the other in terms of improving symptoms, left ventricular function, or prognosis. A number of comparative studies have been performed with metoprolol, a beta1-selective second-generation beta blocker, and carvedilol, a nonselective and vasodilatative third-generation beta blocker. This review will focus on the different pharmacological profiles of carvedilol and metoprolol as well as on the clinical consequences derived from these differences. The results indicate that in some studies carvedilol is superior to metoprolol in improving left ventricular ejection fraction. However, because there is no conclusive evidence that carvedilol is superior to metoprolol in terms of prognosis, it is not justified to substitute metoprolol with carvedilol. Comparative data on mortality reduction are not available before termination of the Carvedilol or Metoprolol European Trial. Nevertheless, the different effects of both beta blockers on the beta-adrenergic system have an impact on tolerability and beta-adrenergic responsiveness and thus exercise tolerance in heart-failure patients.

High-dose methotrexate (HDMTX) is a component of many cancer treatment regimens. Despite careful management, delayed renal clearance, followed by extremely high serum levels with potentially life-threatening toxicity can occur. In the present study, we report our results of carboxypeptidase-G2 (CPDG2) rescue in 8 patients with delayed methotrexate elimination and renal impairment after HDMTX therapy for lymphoma or osteosarcoma. A dose of 50 U/kg CPDG2 was administered. MTX plasma levels decreased rapidly and recovery of renal function was observed in all patients. No patient developed severe WHO grade 4 MTX toxicity. CPDG2 provides an alternative route of MTX elimination by converting it to inactive and non-toxic metabolites. CPDG2 rescue was well tolerated, safe and very effective in preventing severe or life-threatening MTX toxicity.

2831 Introduction Prognosis and need of treatment in CLL is currently determined by clinical staging systems of Binet and Rai. Recent research has focused on prognostic factors that may predict a poor prognosis independent of the clinical stage. Markers which have shown independent prognostic information are serum parameters and genetic factors (genomic aberrations, IgHV and p53 mutational status). To investigate the relevance of these different factors, we performed a pooled analysis using the data of three multicenter German CLL Study Group phase III trials (CLL1, CLL4 and CLL8). Based on this analysis we propose a prognostic score for previously untreated patients with early and advanced CLL. Material and Methods Patients were recruited between 1997 and 2006 into three phase III trials: 715 in CLL1 (“watch and wait” versus fludarabine (F)), 362 in CLL4 (F versus F and cyclophosphamide (FC)) and 817 patients in the CLL8 trial (FC versus FC and rituximab (FCR)). Serum parameters and genetic factors were centrally analyzed prior to treatment. The main end point of all statistical analyses was overall survival. First, univariate analyses were performed including variables of different groups such as baseline characteristics, stage of disease, laboratory results, molecular cytogenetics, mutational status and serum parameters. Next, multivariate Cox regressions were applied including all parameters that showed a significant association with overall survival in univariate analyses. To create a prognostic score we developed a weighted grading algorithm for independent factors based on ranges of hazard ratios. Finally, a prognostic score was defined as the sum of single ratings of adverse factors. According to this score, four different risk groups for overall survival could be identified. Results In total 1948 patients were eligible for the pooled analysis with a median age of 60 years (range, 30 to 81 years). After a median observation time of 63.4 months 485 deaths were reported. At study entry, 799 patients (42.4%) were at Binet stage A, 717 (38.0%) at Binet stage B and 370 (19.6%) at Binet stage C. Almost all considered variables were significantly associated with outcome and therefore included in the multivariate analysis. Based on the data of 1223 patients for whom all parameters were available, multivariate Cox regressions were performed and identified gender, age, ECOG score, del(17p), del(11q), IgHV mutational status, serum β 2 -microglobulin and serum thymidine kinase as independent factors for overall survival. Deletion 17p was the strongest adverse factor. Neither the clinical staging (Rai, Binet) nor the treatment modality were independent prognostic factors for overall survival. Similarly, the time interval between first diagnosis and study entry was not an independent prognostic factor. Due to the great differences between hazard ratios of independent factors, we developed a weighted grading system based on a simple algorithm to assign an individual grade to each adverse factor. By using this weighted grading, four different prognostic groups could be separated: low risk (score 0 – 2), intermediate risk (score 3 – 5), high risk (score 6 – 10) and very high risk (score 11 – 14) (figure 1). Overall survival rates were significantly different for these four groups with 95.2%, 86.9%, 67.7% and 18.7% survival after 5 years for the low, intermediate, high and very high risk group, respectively (p Conclusion While Binet and Rai staging systems may remain important for the initial clinical assessment due to their simplicity, our prognostic score using a weighted combination of genetic and serum markers is superior to predict the overall survival of CLL patients. Disclosures: Pflug: Hoffmann-la Roche: Travel grant; Mundipharma: Travel grant. Eichhorst: Hoffmann La Roche: Honoraria, Research Funding, Travel Grants; Mundipharma: Research Funding, Travel Grants; Gilead: Consultancy. Bergmann: Celgene: Honoraria. Dohner: Hoffmann-la Roche: Research Funding. Stilgenbauer: Hoffmann La Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Travel Grants. Fischer: Hoffmann La Roche: Travel Grants. Hallek: Hoffmann-la Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees.

Introduction Physical activity is associated with decreased cancer (recurrence) risk and a reduction in treatment-specific side effects. Exercise modulates cytokine expression and shows beneficial effects on cancer patients’ immune system. We investigated the following: (i) whether Non-Hodgkin-Lymphoma patients have increased serum macrophage migration inhibiting factor (MIF) and Interleukin-6 (IL-6) levels after immunochemotherapy; (ii) whether physical activity influences cytokine serum levels; and (iii) whether serum cytokine levels are associated with histone modifications in tumor-competitive immune cells. Methods Thirty patients and 10 healthy controls were randomised into an intervention and a control group. Participants of the intervention group exercised once for 30 min at moderate intensity on a bicycle ergometer. Blood samples were collected twice, before and after the intervention. MIF and IL-6 serum concentrations were detected by ELISA. Natural killer cells and CD8+ T-lymphocytes were isolated by magnetic labeled cell sorting. Isolated cells were stained and analyzed for global histone acetylation at histone 4, lysine 5 and histone three, lysine 9. Results Patients showed higher serum MIF and IL-6 baseline levels, and reduced NK-cell histone acetylation, indicating a reduced transcriptional activity of tumor-competitive lymphocytes. Changes in MIF correlated with altered NK-cell histone acetylation, leading to the hypothesis that MIF impacts NK-cells via epigenetic modifications. Further, the exercise intervention was associated with an increase in IL-6 and CD8+ T-lymphocyte histone acetylation. Conclusions We conclude that exercise induces changes in cytokine levels, thereby possibly affecting epigenetic patterns and activity of tumor-competitive lymphocytes.