Obesity is associated with an impaired survival in lymphoma patients undergoing autologous stem cell transplantation
Autoři:
Sebastian Scheich aff001; Julius C. Enßle aff001; Victoria T. Mücke aff002; Fabian Acker aff001; Lukas Aspacher aff001; Sebastian Wolf aff001; Anne C. Wilke aff001; Sarah Weber aff001; Uta Brunnberg aff001; Hubert Serve aff001; Björn Steffen aff001
Působiště autorů:
Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany
aff001; Department of Gastroenterology, Hepatology, Pulmonology and Endocrinology, University Hospital Frankfurt, Frankfurt am Main, Germany
aff002
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225035
Souhrn
Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a potentially curative treatment option for relapsed and refractory lymphomas. Obesity displays an emerging epidemic risk factor for global mortality and is associated with an increased mortality in cancer patients. To date, the impact of obesity on the outcome of lymphoma patients undergoing auto-HSCT is understudied. We conducted a retrospective single-center study assessing 119 lymphoma patients who underwent auto-HSCT. Overall survival (OS) served as the primary endpoint whereas progression free survival (PFS), cumulative incidence of non-relapse related mortality (NRM) and cumulative incidence of relapse were analyzed as secondary endpoints. Obese patients (Body mass index, BMI≥30) had significantly lower OS (45.3% vs. 77.9%; p = 0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to non-obese patients at 48 months post-transplantation. The cumulative incidence of NRM displayed no significant differences while the cumulative incidence of relapse was significantly increased in patients with BMI≥30 (66.2% vs. 21.5%; p<0.001). Patients with a BMI<25 and overweight patients (BMI 25–30; 76.1% vs. 80.9%; p = 0.585), showed no significant difference in OS, whereas patients with BMI≥30 exhibited significant lower OS when compared to either of both groups (76.1% vs. 45.3%; p = .0.021 and 80.9% vs. 45.3%; p = 0.010). Furthermore, in a multivariate analysis, obesity was identified as an independent risk factor for death (Hazard ratio 2.231; 95% CI 1.024 to 4.860; p = 0.043). Further studies are needed to evaluate the reasons for the higher relapse rate causing higher mortality in obese patients.
Klíčová slova:
Body Mass Index – Cancer risk factors – Cancer treatment – Chemotherapy – Lymphomas – Obesity – Toxicity
Zdroje
1. Hitz F, Connors JM, Gascoyne RD, Hoskins P, Moccia A, Savage KJ, et al. Outcome of patients with primary refractory diffuse large B cell lymphoma after R-CHOP treatment. Ann Hematol. 2015;94(11):1839–43. Epub 2015/08/08. doi: 10.1007/s00277-015-2467-z 26246466.
2. Costa LJ, Maddocks K, Epperla N, Reddy NM, Karmali R, Umyarova E, et al. Diffuse large B-cell lymphoma with primary treatment failure: Ultra-high risk features and benchmarking for experimental therapies. Am J Hematol. 2017;92(2):161–70. Epub 2016/11/24. doi: 10.1002/ajh.24615 27880984; PubMed Central PMCID: PMC5549936.
3. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995;333(23):1540–5. Epub 1995/12/07. doi: 10.1056/NEJM199512073332305 7477169.
4. Hutchings M, Ladetto M, Buske C, de Nully Brown P, Ferreri AJM, Pfreundschuh M, et al. ESMO Consensus Conference on malignant lymphoma: management of 'ultra-high-risk' patients. Ann Oncol. 2018;29(8):1687–700. Epub 2018/06/21. doi: 10.1093/annonc/mdy167 29924296.
5. Caballero MD, Perez-Simon JA, Iriondo A, Lahuerta JJ, Sierra J, Marin J, et al. High-dose therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group. Ann Oncol. 2003;14(1):140–51. Epub 2002/12/19. doi: 10.1093/annonc/mdg008 12488306.
6. Kuruvilla J. The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma. Blood. 2016;127(17):2093–100. Epub 2016/03/19. doi: 10.1182/blood-2015-11-624320 26989206.
7. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81. Epub 2014/06/02. doi: 10.1016/S0140-6736(14)60460-8 24880830; PubMed Central PMCID: PMC4624264.
8. Gonzalez-Muniesa P, Martinez-Gonzalez MA, Hu FB, Despres JP, Matsuzawa Y, Loos RJF, et al. Obesity. Nat Rev Dis Primers. 2017;3:17034. Epub 2017/06/16. doi: 10.1038/nrdp.2017.34 28617414.
9. Bocquier A, Vieux F, Lioret S, Dubuisson C, Caillavet F, Darmon N. Socio-economic characteristics, living conditions and diet quality are associated with food insecurity in France. Public Health Nutr. 2015;18(16):2952–61. Epub 2015/01/08. doi: 10.1017/S1368980014002912 25563304.
10. Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 2011;378(9793):815–25. Epub 2011/08/30. doi: 10.1016/S0140-6736(11)60814-3 21872750.
11. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D, et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ. 2007;335(7630):1134. Epub 2007/11/08. doi: 10.1136/bmj.39367.495995.AE 17986716; PubMed Central PMCID: PMC2099519.
12. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78. Epub 2008/02/19. doi: 10.1016/S0140-6736(08)60269-X 18280327.
13. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet. 2014;384(9945):755–65. Epub 2014/08/19. doi: 10.1016/S0140-6736(14)60892-8 25129328; PubMed Central PMCID: PMC4151483.
14. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38. Epub 2003/04/25. doi: 10.1056/NEJMoa021423 12711737.
15. Larsson SC, Wolk A. Body mass index and risk of non-Hodgkin's and Hodgkin's lymphoma: a meta-analysis of prospective studies. Eur J Cancer. 2011;47(16):2422–30. Epub 2011/07/08. doi: 10.1016/j.ejca.2011.06.029 21733676.
16. Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF, et al. Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014(48):130–44. Epub 2014/09/01. doi: 10.1093/jncimonographs/lgu013 25174034; PubMed Central PMCID: PMC4155467.
17. Navarro WH, Loberiza FR Jr., Bajorunaite R, van Besien K, Vose JM, Lazarus HM, et al. Effect of body mass index on mortality of patients with lymphoma undergoing autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2006;12(5):541–51. Epub 2006/04/26. doi: 10.1016/j.bbmt.2005.12.033 16635789.
18. Tarella C, Caracciolo D, Gavarotti P, Argentino C, Zallio F, Corradini P, et al. Overweight as an adverse prognostic factor for non-Hodgkin's lymphoma patients receiving high-dose chemotherapy and autograft. Bone Marrow Transplant. 2000;26(11):1185–91. Epub 2001/01/10. doi: 10.1038/sj.bmt.1702692 11149729.
19. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309–32. Epub 2008/06/10. doi: 10.1016/j.ajic.2008.03.002 18538699.
20. Apovian CM. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. 2016;22(7 Suppl):s176–85. Epub 2016/06/30. 27356115.
21. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M, Educational, et al. ESPEN guidelines for nutrition screening 2002. Clin Nutr. 2003;22(4):415–21. Epub 2003/07/26. doi: 10.1016/s0261-5614(03)00098-0 12880610.
22. Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. 2014;25(10):1901–14. Epub 2014/04/29. doi: 10.1093/annonc/mdu042 24769692; PubMed Central PMCID: PMC4176449.
23. Hohloch K, Altmann B, Pfreundschuh M, Loeffler M, Schmitz N, Zettl F, et al. Obesity negatively impacts outcome in elderly female patients with aggressive B-cell lymphomas treated with R-CHOP: results from prospective trials of the German high grade non-Hodgkin's lymphoma trial group. Br J Haematol. 2018;180(2):236–45. Epub 2017/12/02. doi: 10.1111/bjh.15029 29193018.
24. Epperla N, Badar T, Szabo A, Vaughn J, Borson S, Saini NY, et al. Postrelapse survival in diffuse large B-cell lymphoma after therapy failure following autologous transplantation. Blood Adv. 2019;3(11):1661–9. Epub 2019/06/07. doi: 10.1182/bloodadvances.2019000102 31167818; PubMed Central PMCID: PMC6560348.
25. Broccoli A, Zinzani PL. The role of transplantation in Hodgkin lymphoma. Br J Haematol. 2019;184(1):93–104. Epub 2018/11/09. doi: 10.1111/bjh.15639 30407612.
26. Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387(10026):1377–96. Epub 2016/04/27. doi: 10.1016/S0140-6736(16)30054-X 27115820.
27. Haslam DW, James WP. Obesity. Lancet. 2005;366(9492):1197–209. Epub 2005/10/04. doi: 10.1016/S0140-6736(05)67483-1 16198769.
28. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289(1):76–9. Epub 2002/12/31. doi: 10.1001/jama.289.1.76 12503980.
29. Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300(23):2754–64. Epub 2008/12/18. doi: 10.1001/jama.2008.824 19088353; PubMed Central PMCID: PMC3093051.
30. International Diabetes Federation. IDF Diabetes Atlas Brussels, Belgium. 2017.
31. Iyengar NM, Hudis CA, Dannenberg AJ. Obesity and cancer: local and systemic mechanisms. Annu Rev Med. 2015;66:297–309. Epub 2015/01/15. doi: 10.1146/annurev-med-050913-022228 25587653.
32. Howe LR, Subbaramaiah K, Hudis CA, Dannenberg AJ. Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer. Clin Cancer Res. 2013;19(22):6074–83. Epub 2013/08/21. doi: 10.1158/1078-0432.CCR-12-2603 23958744; PubMed Central PMCID: PMC3891839.
33. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1–2):20–44. Epub 2014/01/21. doi: 10.1016/j.cell.2013.12.012 24439368; PubMed Central PMCID: PMC3934003.
34. Khandekar MJ, Cohen P, Spiegelman BM. Molecular mechanisms of cancer development in obesity. Nat Rev Cancer. 2011;11(12):886–95. Epub 2011/11/25. doi: 10.1038/nrc3174 22113164.
35. Park J, Euhus DM, Scherer PE. Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr Rev. 2011;32(4):550–70. Epub 2011/06/07. doi: 10.1210/er.2010-0030 21642230; PubMed Central PMCID: PMC3369575.
36. Lyman GH, Sparreboom A. Chemotherapy dosing in overweight and obese patients with cancer. Nat Rev Clin Oncol. 2013;10(8):451–9. Epub 2013/07/17. doi: 10.1038/nrclinonc.2013.108 23856744.
37. Pai MP. Drug dosing based on weight and body surface area: mathematical assumptions and limitations in obese adults. Pharmacotherapy. 2012;32(9):856–68. Epub 2012/06/20. doi: 10.1002/j.1875-9114.2012.01108.x 22711238.
38. Field KM, Kosmider S, Jefford M, Michael M, Jennens R, Green M, et al. Chemotherapy dosing strategies in the obese, elderly, and thin patient: results of a nationwide survey. J Oncol Pract. 2008;4(3):108–13. Epub 2008/05/01. doi: 10.1200/JOP.0832001 20856612; PubMed Central PMCID: PMC2794002.
39. Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004;58(2):119–33. Epub 2004/07/17. doi: 10.1111/j.1365-2125.2004.02157.x 15255794; PubMed Central PMCID: PMC1884581.
40. Blijlevens N, Schwenkglenks M, Bacon P, D'Addio A, Einsele H, Maertens J, et al. Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy—European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol. 2008;26(9):1519–25. Epub 2008/02/13. doi: 10.1200/JCO.2007.13.6028 18268357.
41. Bubalo J, Carpenter PA, Majhail N, Perales MA, Marks DI, Shaughnessy P, et al. Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee. Biol Blood Marrow Transplant. 2014;20(5):600–16. Epub 2014/01/28. doi: 10.1016/j.bbmt.2014.01.019 24462742.
42. Nikolousis E, Nagra S, Paneesha S, Delgado J, Holder K, Bratby L, et al. Allogeneic transplant outcomes are not affected by body mass index (BMI) in patients with haematological malignancies. Ann Hematol. 2010;89(11):1141–5. Epub 2010/06/15. doi: 10.1007/s00277-010-1001-6 20544351.
43. Dickson TM, Kusnierz-Glaz CR, Blume KG, Negrin RS, Hu WW, Shizuru JA, et al. Impact of admission body weight and chemotherapy dose adjustment on the outcome of autologous bone marrow transplantation. Biol Blood Marrow Transplant. 1999;5(5):299–305. Epub 1999/10/26. 10534060.
44. Costa LJ, Micallef IN, Inwards DJ, Johnston PB, Porrata LF, Litzow MR, et al. Effect of the dose per body weight of conditioning chemotherapy on severity of mucositis and risk of relapse after autologous haematopoietic stem cell transplantation in relapsed diffuse large B cell lymphoma. Br J Haematol. 2008;143(2):268–73. Epub 2008/08/14. doi: 10.1111/j.1365-2141.2008.07342.x 18699848.
45. Brunstein CG, Pasquini MC, Kim S, Fei M, Adekola K, Ahmed I, et al. Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019;25(3):480–7. Epub 2018/11/14. doi: 10.1016/j.bbmt.2018.11.005 30423481; PubMed Central PMCID: PMC6445718.
46. Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2012;30(13):1553–61. Epub 2012/04/05. doi: 10.1200/JCO.2011.39.9436 22473167.
47. Jain R, Chung SM, Jain L, Khurana M, Lau SW, Lee JE, et al. Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther. 2011;90(1):77–89. Epub 2011/06/03. doi: 10.1038/clpt.2011.104 21633345.
48. Chan H, Jackson S, McLay J, Knox A, Lee J, Wang S, et al. Obese non-Hodgkin lymphoma patients tolerate full uncapped doses of chemotherapy with no increase in toxicity, and a similar survival to that seen in nonobese patients. Leuk Lymphoma. 2016;57(11):2584–92. Epub 2016/03/05. doi: 10.3109/10428194.2016.1151508 26943235.
Článek vyšel v časopise
PLOS One
2019 Číslo 11
- Řekněte mi, co jíte, a já vám řeknu, jaká je úroveň vaší kognice
- Duševní onemocnění se u teenagerů přenáší v rámci školní třídy
- Od kostiček k lidské kůži. Jak si postavit 3D biotiskárnu?
- Pomohou nám s detekcí karcinomu plic i včely?
- Původní český test ALBA pro odhalení mírných kognitivních deficitů získal certifikaci MZ ČR
Nejčtenější v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy