Physical exercise recommendations for patients with chronic myeloid leukemia based on individual preferences identified in a large international patient survey study of the East German Study Group for Hematology and Oncology (OSHO #97).

Background: Tyrosine kinase inhibitors (TKIs) have significantly lowered mortality of chronic myeloid leukemia (CML) patients adjusting life expectancy to that of the standard population. However, CML and its treatment with TKIs causes a high disease burden. Physical exercise (PE) could be a non-pharmacological approach to reducing these and improving quality of life. Purpose: The aim of this study was to determine the individual disease burden as well as PE preferences of CML patients and to deduce thereof specific PE recommendations. Methods: This multicenter survey was conducted in cooperation with the LeukaNET/Leukemia-patient network including CML patients aged ≥18 years (German Registry of Clinical Trials, DRKS00023698). The severity of selected symptoms was assessed using the adapted Myeloproliferative Neoplasms Symptom Assessment Form: 0 (absent), 1-30 (mild), 31-70 (moderate), or 71-100 (severe). Information about patients' PE needs and preferences depending on their motivation was recorded. Results: A total of 212 questionnaires were analyzed (52% female, median age 54 years). The prevalence of moderate-to-severe symptoms was 49% for fatigue, 40% for musculoskeletal pain, and 37% for concentration problems. Other commonly reported symptoms included skin reactions (42%) and weight gain (24%). The proportion of overweight/obese patients was 52%. Half of all respondents requested more information regarding PE. Patients with CML preferred individual training (82%), located outdoors (71%), at home (47%), or in an indoor swimming pool (31%). Regarding the training frequency, sports-inactive patients preferred a frequency of 1-2 training sessions per week, whereas sports-active patients preferred 3-4 sessions per week (p <0.001). Sports-inactive patients preferred a training time of 15-45 minutes, while sports-active patients preferred 30-60 minutes (p = 0.002). Subsequently, PE recommendations were developed for patients with CML. Combined resistance and endurance training (moderate intensity twice per week for 30 minutes) was recommended for beginners. Obese patients should prioritize joint-relieving sports. To reduce the risk of skin reactions, direct sunlight and possibly water sports should be avoided, and UV protection should be used. Conclusion: Counseling and motivation of CML patients to be physically active should be part of the standard of care as well as support for implementation.

Physical exercise recommendations for patients with polycythemia vera based on preferences identified in a large international patient survey study of the East German Study Group for Hematology and Oncology (OSHO #97).

BACKGROUND: Exercise therapy during cancer treatment reduces symptom burden and improves quality of life (QoL). Polycythemia vera (PV) is a myeloproliferative neoplasia associated with good overall survival (up to decades) but a significant symptom burden, including thromboembolic events and dysesthesias. There are no specific exercise recommendations for patients with PV. Thus, we aimed to determine the exercise preferences of patients with PV and to derive specific recommendations based on the most commonly reported symptoms. METHODS: This multicenter survey included patients with PV ≥18 years old. Demographic, clinical, and disease burden data were collected. The severity of selected symptoms was assessed using the adapted Myeloproliferative Neoplasms Symptom Assessment Form: 0 (absent), 1-30 (mild), 31-70 (moderate), or 71-100 (severe). The patients' information needs about physical activity (PA) and exercise preferences were recorded depending on their motivation and analyzed with regard to demographic aspects. RESULTS: The sample comprised 182 patients (68% female, 61 ± 12 years). The prevalence of moderate-to-severe symptoms was 60% for fatigue, 44% for concentration problems, and 35% for bone/muscle pain. Other commonly reported symptoms included skin reactions (49%), splenomegaly (35%), and increased bleeding tendency (28%). Overall, 67% of respondents requested more information regarding PA. Patients with PV preferred individual training (79%) located outdoors (79%) or at home (56%). Regarding the amount of training, sports-inactive patients preferred a frequency of 1-2 times/week and session durations of 15-45 min, whereas sports-active patients preferred 3-4 times/week and 30-60 min (p < 0.001). Higher sport-inactiveness was observed in patients with lower educational level compared to patients with higher educational level (69% vs. 50%, p = 0.021). For beginners, combined resistance-endurance (circuit) training two times/week, which can be performed outdoors or at home, should be recommended. In the case of splenomegaly or bleeding symptoms, exercises with a low injury risk should be chosen. CONCLUSION: PA is important for patients with PV; therefore, counseling should be integrated into the treatment plan. Specifically, patients with low educational level should be addressed. Prospective studies are warranted to evaluate the effects of the novel exercise recommendations.

Association Between Cancer-Related Fatigue and Falls in Patients With Myeloproliferative Neoplasms: Results of a Multicenter Cross-Sectional Survey From the East German Study Group for Hematology and Oncology (OSHO #97).

OBJECTIVE: This study retrospectively examined the association between cancer-related fatigue (CrF) and the number of falls during the last 12 months in patients with myeloproliferative neoplasms (MPNs). METHODS: A multicenter, 1-time anonymous survey was conducted using analog and digital questionnaires. Sex-stratified multinomial logistic regression analysis was applied to investigate the association between CrF and number of falls. All analyses were adjusted for age, school education, body mass index, MPN subtype, and quality of life. RESULTS: The final sample comprised 688 patients (mean age 57.4 ± 13.8, 62.4% women). The fall rate was 16.2% in women and 12.2% in men (P = .153). There were no differences between women and men in terms of CrF between individuals with more than 1 fall, whereas women with 1 fall had a higher CrF compared to those without a fall (RRR = 1.019; 95% CI [1.002-1.039]), respectively. CONCLUSION: CrF increases the risk of falls in women with MPN. Physicians should evaluate and manage CrF symptoms and implement fall prevention strategies for those who are at increased risk. Further research is needed to better understand the effects of CrF on gait performance and associated fall risk.

Anxieties, age and motivation influence physical activity in patients with myeloproliferative neoplasms - a multicenter survey from the East German study group for hematology and oncology (OSHO #97).

Background: Physical activity (PA) is a non-pharmacological approach to alleviate symptom burden and improve health-related quality of life (HrQoL) in cancer patients (pts). Whether pts with myeloproliferative neoplasms (MPN) PA behavior changes due to symptom burden and/or knowledge of the putative beneficial effects of PA has not yet been investigated. Methods: We performed a large questionnaire study in MPN pts. Self-reported PA behavior and potential influencing factors of 634 MPN pts were analyzed. Questionnaires were used to assess demographics, anxiety, severity of symptoms, HrQoL, current level of everyday and sports activities, and the level of information regarding the importance/possibilities of PA. According to their PA, the pts were assigned to the three groups: "inactive", "non-targeted active", and "sporty active" and compared with each other. Results: Key findings are that in 73% of the pts, the disease had an impact on PA, with 30% of pts reducing their PA. The prevalence of anxieties (e.g., occurrence of thrombosis and bleeding) regarding PA was 45%. Sporty active pts had a lower symptom burden and better HrQoL (p ≤ 0.001) compared to the other groups. Inactive pts were significantly older and had a higher body mass index than sporty active pts. Inactive and non-targeted active pts felt less informed about the importance/possibilities of PA (p = 0.002). Conclusion: Our results suggest that especially older and non-sporty MPN pts could benefit from motivational as well as disease-specific PA information. This study was registered at the German Registry of Clinical Trials, DRKS00023698.

Screening and differential diagnosis of renal light chain-associated diseases.

BACKGROUND: Renal involvement in the light chain-associated diseases multiple myeloma (MM), amyloidosis (AL) and monoclonal immune position disease (MIDD) is common and differential diagnosis usually requires renal biopsy. The aim of this study was to investigate if noninvasive methods are viable to identify and differentiate between the various types of kidney diseases. PATIENTS AND METHODS: All patients with a light chain-associated disease admitted to our center from 1996 to 2008 were retrospectively evaluated. Renal biopsy data were correlated with proteinuria findings. RESULTS: Only the ratio of free κ/λ light chains showed a good sensitivity for myeloma cast nephropathy (MCN), AL and MIDD. The λ light chain was characteristic for AL, the κ light chain dominated in MIDD. Renal function at the time of diagnosis was worst in MIDD. MCN presented with a proteinuria of > 3.5 g/g creatinine. In contrast, a higher proteinuria was found in AL or MIDD. Whereas the κ/λ ratio in the urine was pathological for all three diseases, extremely high or low ratios indicated the presence of MCN. However, in AL or MIDD, the ratio was only moderately elevated. CONCLUSION: A noninvasive differentiation between MCN and other forms of renal light chain disease is possible.

Remission with Imatinib mesylate treatment in a patient with initially unresectable dermatofibrosarcoma protuberans--a case report.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, malignant dermal mesenchymal neoplasm characterized by a slow, infiltrative growth. These neoplasms have a high tendency to recur locally after surgical excision. However, metastasizing cases are exceedingly rare. Cytogenetically, DFSP is characterized by a t(17;22)(22;q13) aberration with fusion of the COL1A1 gene on chromosome 17 with the PDGFB gene on chromosome 22. Here, we report on a successful treatment of a patient with a targeted therapy using the tyrosine kinase inhibitor Imatinib mesylate in neoadjuvant intention. PATIENTS AND METHODS: A patient with recurrent and initially unresectable but non-metastatic DFSP of the scalp received Imatinib over 3 months with increasing dosage from 400 mg/day to 800 mg/day orally. Due to the location of the DFSP in our patient, we intended to decrease tumor size preoperatively to allow complete surgical resection. Response to therapy was assessed by computed tomography. RESULTS: Preoperative treatment with Imatinib resulted in decrease of tumor size by over 60% in the greatest dimension during 3 months of therapy, enabling the complete resection of the DFSP by radical surgery with achieving an acceptable cosmetic result. Surgery was followed by adjuvant Imatinib therapy over 6 months. CONCLUSIONS: Imatinib mesylate is effective in neoadjuvant treatment of primary unresectable dermatofibrosarcoma protuberans and can be considered as a useful option in the therapy regimen.

Formation of the killer Ig-like receptor repertoire on CD4+CD28null T cells.

Killer Ig-like receptors (KIRs) are expressed on CD4(+)CD28(null) T cells, a highly oligoclonal subset of T cells that is expanded in patients with rheumatoid arthritis. It is unclear at what stage of development these T cells acquire KIR expression. To determine whether KIR expression is a consequence of clonal expansion and replicative senescence, multiple CD4(+)CD28(null) T cell clones expressing the in vivo dominant TCR beta-chain sequences were identified in three patients and analyzed for their KIR gene expression pattern. Based on sharing of TCR sequences, the clones were grouped into five clone families. The repertoire of KIRs was diverse, even within each clone family; however, the gene expression was not random. Three particular receptors, KIR2DS2, KIR2DL2, and KIR3DL2, had significant differences in gene expression frequencies between the clone families. These data suggest that KIRs are successively acquired after TCR rearrangement, with each clone family developing a dominant expression pattern. The patterns did not segregate with the individual from whom the clones were derived, indicating that peripheral selection in the host environment was not a major shaping force. Several models were examined using a computer algorithm that was designed to simulate the expression of KIRs at various times during T cell proliferation. The computer simulations favored a model in which KIR gene expression is inducible for a limited time during the initial stages of clonal expansion.