Skip to main content

Impact of cachexia on outcomes in aggressive lymphomas

Annals of Hematology volume 96, pages 951–956 (2017)Cite this article

Abstract

Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87–93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into “non-cachectic” (CXI ≥49.8, n = 41) and “cachectic” (CXI <49.8, n = 40) groups. Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR = 4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  1. Shipp MA (1994) Prognostic factors in aggressive non-Hodgkin’s lymphoma: who has “high-risk” disease? Blood 83(5):1165–1173

    CAS  PubMed  Google Scholar 

  2. Evans WJ, Morley JE, Argilés J et al (2008) Cachexia: a new definition. Clin Nutr 27(6):793–799

    CAS  Article  PubMed  Google Scholar 

  3. Staal-van den Brekel AJ, Dentener MA, Schols AM, Buurman WA, Wouters EF (1995) Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J Clin Oncol 13(10):2600–2605

    CAS  Article  PubMed  Google Scholar 

  4. Kuroda K, Nakashima J, Kanao K et al (2007) Interleukin 6 is associated with cachexia in patients with prostate cancer. Urology 69(1):113–117

    Article  PubMed  Google Scholar 

  5. Demetrius LA, Coy JF, Tuszynski JA. (2010) Cancer proliferation and therapy: the Warburg effect and quantum metabolism. Theor Biol Med Model. 7:2. doi:10.1186/1742-4682-7-2

  6. Fredrix EW, Soeters PB, Wouters EF, Deerenberg IM, von Meyenfeldt MF, Saris WH (1990) Energy balance in relation to cancer cachexia. Clin Nutr 9(6):319–324

    CAS  Article  PubMed  Google Scholar 

  7. Petruzzelli M, Wagner EF (2016) Mechanisms of metabolic dysfunction in cancer-associated cachexia. Genes Dev 30(5):489–501

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Falconer JS, Fearon KC, Plester CE, Ross JA, Carter DC (1994) Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg 219(4):325–331

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Ohnuma T. 2003 Manifestations of Cachexia. Holland-Frei Cancer Medicine. Hamilton

  10. Project TIN-HsLPF (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. The international non-Hodgkin’s lymphoma prognostic factors project. N Engl J Med 329:987–994

    Article  Google Scholar 

  11. Perry AM, Alvarado-Bernal Y, Laurini JA et al (2014) MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab. Br J Haematol 165(3):382–391

    CAS  Article  PubMed  Google Scholar 

  12. Lenz G, Wright G, Dave SS et al (2008) Lymphoma/leukemia molecular profiling project. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 359(22):2313–2323

    CAS  Article  PubMed  Google Scholar 

  13. Uddin S, Bu R, Ahmed M, Hussain AR, Ajarim D, Al-Dayel F et al (2010) Leptin receptor expression and its association with PI3K/AKT signaling pathway in diffuse large B-cell lymphoma. Leukemia & Lymphoma 51(7):1305–1314

    CAS  Article  Google Scholar 

  14. Carbone A, Gloghini A, Kwong Y-L, Younes A (2014) Diffuse large B cell lymphoma: using pathologic and molecular biomarkers to define subgroups for novel therapy. Ann Hematol 93(8):1263–1277

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Jafri SH, Previgliano C, Khandelwal K, Shi R (2015) Cachexia index in advanced non-small-cell lung cancer patients. Clin Med Insights Oncol 9:87–93

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282

    CAS  Article  PubMed  Google Scholar 

  17. Prado CM, Sawyer MB, Ghosh S et al (2013) Central tenet of cancer cachexia therapy: do patient with advanced cancer have exploitable anabolic potential? Am J Clin Nutr 98:1012–1019

    CAS  Article  PubMed  Google Scholar 

  18. Camus V, Lanic H, Kraut J et al (2014) Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Eur J Haematol 93(1):9–18

    CAS  Article  PubMed  Google Scholar 

  19. Lanic H, Kraut-Tauzia J, Modzelewski R, Clatot F, Mareschal S, Picquenot JM, Stamatoullas A, Leprêtre S, Tilly H, Jardin F (2014) Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Leuk Lymphoma 55(4):817–823

    CAS  Article  PubMed  Google Scholar 

  20. Gupta D, Lis CG (2010) Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 9:69

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lin GN, Peng JW, Liu PP, Liu DY, Xiao JJ, Chen XQ (2014) Elevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment. Asia Pac J Clin Oncol. doi:10.1111/ajco.12273. [Epub ahead of print]

  22. Skibola CF, Curry JD, Nieters A (2007 Jul) Genetic susceptibility to lymphoma. Haematologica 92(7):960–969

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Charbonneau B, Maurer MJ, Ansell SM et al (2012) Pretreatment circulating serum cytokines associated with follicular and diffuse large B-cell lymphoma: a clinic-based case-control study. Cytokine 60(3):882–889

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Bonetto A, Aydogdu T, Jin X et al (2012) JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab 303(3):E410–E421

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Bonetto A, Penna F, Aversa Z et al (2013) Early changes of muscle insulin-like growth factor-1 and myostatin gene expression in gastric cancer patients. Muscle Nerve 48(3):387–392

    CAS  Article  PubMed  Google Scholar 

  26. Karmali R, Dalovisio A, Borgia JA et al (2015) All in the family: clueing into the link between metabolic syndrome and hematologic malignancies. Blood Rev 29(2):71–80

    CAS  Article  PubMed  Google Scholar 

  27. Karmali R, Paganessi LA, Frank RR, Jagan S, Larson ML, Venugopal P, Gregory SA, Christopherson KW 2nd (2013) Aggressive disease defined by cytogenetics is associated with cytokine dysregulation in CLL/SLL patients. J Leukoc Biol (1):161–70

  28. Vishwamitra D, Shi P, Wilson D et al (2011) Expression and effects of inhibition of type 1 insulin-like growth factor receptor tyrosine kinase in mantle cell lymphoma. Heamatolgica 96(6):871–880

    CAS  Article  Google Scholar 

  29. Oliveira AG, Gomes-Marcondes MC (2016) Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats. BMC Cancer 16:418. doi:10.1186/s12885-016-2424-9

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

  1. Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, Chicago, IL, USA

    Reem Karmali, Vineela Chukkapalli, Sunita Nathan, Kelly Szymanski-Grant & Parameswaran Venugopal

  2. Rush University Medical Center, Chicago, IL, USA

    Taha Alrifai, Ibtihaj A. M. Fughhi & Sanjib Basu

  3. University of Illinois, Chicago, IL, USA

    Ronald Ng

  4. Department of Radiology, Rush University Medical Center, Chicago, IL, USA

    Palmi Shah

  5. Division of Hematology, Oncology, Northwestern University, Chicago, IL, USA

    Leo I. Gordon

  6. Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA

    Leo I. Gordon & Frank J. Penedo

  7. Departments of Medical Social Sciences, Psychology & Psychiatry and Behavioral Sciences, Northwestern University, Axis Apartments & Lofts, 446 E Ontario St, Chicago, IL, 60611, USA

    Frank J. Penedo

  8. Departments of Pathology and Biochemistry, Rush University Medical Center, Chicago, IL, USA

    Jeffrey A. Borgia

Authors
  1. Reem Karmali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taha Alrifai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ibtihaj A. M. Fughhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronald Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vineela Chukkapalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Palmi Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sanjib Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sunita Nathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kelly Szymanski-Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Leo I. Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Parameswaran Venugopal
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Frank J. Penedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jeffrey A. Borgia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reem Karmali.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Karmali, R., Alrifai, T., Fughhi, I.A.M. et al. Impact of cachexia on outcomes in aggressive lymphomas. Ann Hematol 96, 951–956 (2017). https://doi.org/10.1007/s00277-017-2958-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-017-2958-1

Keywords

  • Non-Hodgkin lymphomas
  • Cachexia
  • Prognostic factors
  • Pathophysiology
  • DLBCL
  • Outcomes