Predictors of chemotherapy-induced severe anemia in cancer patients receiving chemotherapy

  • Abolfazl Razzaghdoust
  • Bahram MofidEmail author
  • Parvin Peyghambarlou
Original Article



Chemotherapy-induced anemia is a frequent complication of systemic chemotherapy and is associated with decreased functional capacity and quality of life. The objective of this study was to identify the candidate variables most likely to be associated with chemotherapy-induced severe anemia (hemoglobin < 8 g/dL) in patients treated with cytotoxic chemotherapy.


A total of 14 clinical and laboratory covariates were prospectively evaluated at baseline in a cohort of consecutive cancer patients receiving cytotoxic chemotherapy. The anemia risk category for each chemotherapy regimen used was determined based on pivotal trials published in the literature. All regimens were classified to three categories (high risk, intermediate risk, and low risk). Logistic regression analysis adjusted for the regimen risk was used to determine the candidate risk factors associated with chemotherapy-induced anemia.


A total of 305 patients were included in the study. Administration of high-risk regimens (i.e., regimens with ≥ 20% risk of anemia in a pivotal trial) was demonstrated to be a novel independent predictive factor for severe anemia (odds ratio 3.33, p = 0.005). Considering regimen risk as an adjustment factor, 5 readily available predictors including low hemoglobin, body mass index (BMI) less than 23 kg/m2, low hematocrit, high haptoglobin, and high ferritin were associated with the outcome.


The application of these candidate predictors would be helpful in classifying patients at risk for severe anemia, who might be appropriate candidates for prophylactic erythropoietin. Multivariable models including such promising candidate predictors need to be developed.


Cancer Severe anemia Predictor Chemotherapy 



This study is related to the project NO. 1397/69569 from Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. We appreciate the “Student Research Committee” and “Research & Technology Chancellor” in Shahid Beheshti University of Medical Sciences for their financial support of this study. The authors would also like to acknowledge Behnam Daheshpour Charity Organization for supporting this work.

Author contributions

The authors have met all three of the following criteria for authorship, thereby accepting public responsibility for appropriate portions of the content:

1. Substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data

2. Drafting the article or revising it critically for important intellectual content

3. Approval of the version to be published and all subsequent versions

Funding information

This study was supported by the Student Research Committee in Shahid Beheshti University of Medical Sciences, and Behnam Daheshpour Charity Organization.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

520_2019_4780_MOESM1_ESM.docx (135 kb)
ESM 1 (DOCX 134 kb)


  1. 1.
    Repetto L (2009) Incidence and clinical impact of chemotherapy induced myelotoxicity in cancer patients: an observational retrospective survey. Crit Rev Oncol Hematol 72(2):170–179. Google Scholar
  2. 2.
    Wu Y, Aravind S, Ranganathan G, Martin A, Nalysnyk L (2009) Anemia and thrombocytopenia in patients undergoing chemotherapy for solid tumors: a descriptive study of a large outpatient oncology practice database, 2000-2007. Clin Ther 31(Pt 2):2416–2432. Google Scholar
  3. 3.
    Lyman GH, Berndt ER, Kallich JD, Erder MH, Crown WH, Long SR, Lee H, Song X, Finkelstein SN (2005) The economic burden of anemia in cancer patients receiving chemotherapy. Value Health 8(2):149–156. Google Scholar
  4. 4.
    Lind M, Vernon C, Cruickshank D, Wilkinson P, Littlewood T, Stuart N, Jenkinson C, Grey-Amante P, Doll H, Wild D (2002) The level of haemoglobin in anaemic cancer patients correlates positively with quality of life. Br J Cancer 86(8):1243–1249. Google Scholar
  5. 5.
    Glaspy J, Bukowski R, Steinberg D, Taylor C, Tchekmedyian S, Vadhan-Raj S (1997) Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group. J Clin Oncol 15(3):1218–1234. Google Scholar
  6. 6.
    Demetri GD, Kris M, Wade J, Degos L, Cella D (1998) Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 16(10):3412–3425. Google Scholar
  7. 7.
    Caro JJ, Salas M, Ward A, Goss G (2001) Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer 91(12):2214–2221Google Scholar
  8. 8.
    Dranitsaris G, Clemons M, Verma S, Lau C, Vincent M (2005) Chemotherapy-induced anaemia during adjuvant treatment for breast cancer: development of a prediction model. Lancet Oncol 6(11):856–863. Google Scholar
  9. 9.
    Chaumard N, Limat S, Villanueva C, Nerich V, Fagnoni P, Bazan F, Chaigneau L, Dobi E, Cals L, Pivot X (2012) Incidence and risk factors of anemia in patients with early breast cancer treated by adjuvant chemotherapy. Breast 21(4):464–467. Google Scholar
  10. 10.
    Coiffier B, Guastalla JP, Pujade-Lauraine E, Bastit P (2001) Predicting cancer-associated anaemia in patients receiving non-platinum chemotherapy: results of a retrospective survey. Eur J Cancer 37(13):1617–1623Google Scholar
  11. 11.
    Caggiano V, Tannous RE, Gupta S, Fridman M (2002) Chemotherapy-induced moderate to severe anemia in intermediate-grade non-Hodgkin’s lymphoma patients. J Oncol Pharm Pract 8(2–3):73–80. Google Scholar
  12. 12.
    Barrett-Lee PJ, Ludwig H, Birgegard G, Bokemeyer C, Gascon P, Kosmidis PA, Krzakowski M, Nortier JW, Kongable G, Schneider M, Schrijvers D, Van Belle SJ (2006) Independent risk factors for anemia in cancer patients receiving chemotherapy: results from the European Cancer Anaemia Survey. Oncology 70(1):34–48. Google Scholar
  13. 13.
    Vincent M, Dranitsaris G, Verma S, Lau C, Gascon P, Van Belle S, Ludwig H (2007) The development and validation of a prediction tool for chemotherapy-induced anemia in patients with advanced nonsmall cell lung cancer receiving palliative chemotherapy. Support Care Cancer 15(3):265–272. Google Scholar
  14. 14.
    Chao C, Xu L, Family L, Xu H (2016) A risk prediction model for severe chemotherapy-induced anemia in breast cancer patients. Blood 128(22):2399–2399Google Scholar
  15. 15.
    Maccio A, Madeddu C, Gramignano G, Mulas C, Tanca L, Cherchi MC, Floris C, Omoto I, Barracca A, Ganz T (2015) The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study. Haematologica 100(1):124–132. Google Scholar
  16. 16.
    Crawford J, Becker PS, Armitage JO, Blayney DW, Chavez J, Curtin P, Dinner S, Fynan T, Gojo I, Griffiths EA, Hough S, Kloth DD, Kuter DJ, Lyman GH, Mably M, Mukherjee S, Patel S, Perez LE, Poust A, Rampal R, Roy V, Rugo HS, Saad AA, Schwartzberg LS, Shayani S, Talbott M, Vadhan-Raj S, Vasu S, Wadleigh M, Westervelt P, Burns JL, Pluchino L (2017) Myeloid Growth Factors, Version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 15(12):1520–1541 1540–1405Google Scholar
  17. 17.
    Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47(1):8–32. Google Scholar
  18. 18.
    Razzaghdoust A, Mofid B, Moghadam M (2018) Development of a simplified multivariable model to predict neutropenic complications in cancer patients undergoing chemotherapy. Support Care Cancer 26:3691–3699. Google Scholar
  19. 19.
    Blay JY, Le Cesne A, Mermet C, Maugard C, Ravaud A, Chevreau C, Sebban C, Guastalla J, Biron P, Ray-Coquard I (1998) A risk model for thrombocytopenia requiring platelet transfusion after cytotoxic chemotherapy. Blood 92(2):405–410Google Scholar
  20. 20.
    Kuderer NM, Francis CW, Crawford J, Dale DC, Wolff DA, Culakova E, Poniewierski MS, Lyman GH (2006) A prediction model for chemotherapy-associated thrombocytopenia in cancer patients. J Clin Oncol 24(18_suppl):8616–8616. Google Scholar
  21. 21.
    Alexandre J, Rey E, Girre V, Grabar S, Tran A, Montheil V, Rabillon F, Dieras V, Jullien V, Herait P, Pons G, Treluyer JM, Goldwasser F (2007) Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study. Ann Oncol 18(1):168–172. Google Scholar
  22. 22.
    Alexandre J, Gross-Goupil M, Falissard B, Nguyen ML, Gornet JM, Misset JL, Goldwasser F (2003) Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy. Ann Oncol 14(1):36–41Google Scholar
  23. 23.
    Chan A, Chen C, Chiang J, Tan SH, Ng R (2012) Incidence of febrile neutropenia among early-stage breast cancer patients receiving anthracycline-based chemotherapy. Support Care Cancer 20(7):1525–1532. Google Scholar
  24. 24.
    Lyman GH, Abella E, Pettengell R (2014) Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: a systematic review. Crit Rev Oncol Hematol 90(3):190–199. Google Scholar
  25. 25.
    Kalousis A, Prados J, Hilario M (2007) Stability of feature selection algorithms: a study on high-dimensional spaces. Knowl Inf Syst 12(1):95–116Google Scholar
  26. 26.
    Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR (1996) A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 49(12):1373–1379Google Scholar
  27. 27.
    Courvoisier DS, Combescure C, Agoritsas T, Gayet-Ageron A, Perneger TV (2011) Performance of logistic regression modeling: beyond the number of events per variable, the role of data structure. J Clin Epidemiol 64(9):993–1000. Google Scholar
  28. 28.
    Chang J, Couture F, Young S, McWatters KL, Lau CY (2005) Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy. J Clin Oncol 23(12):2597–2605. Google Scholar
  29. 29.
    Lyman GH, Glaspy J (2006) Are there clinical benefits with early erythropoietic intervention for chemotherapy-induced anemia? A systematic review. Cancer 106(1):223–233. Google Scholar
  30. 30.
    Khalafallah AA, Yan C, Al-Badri R, Robinson E, Kirkby BE, Ingram E, Gray Z, Khelgi V, Robertson IK, Kirkby BP (2016) Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomised controlled trial. Lancet Haematol 3(9):e415–e425. Google Scholar
  31. 31.
    Berlin NI, Hyde GM, Parsons RJ, Lawrence JH (1955) The blood volume in cancer. Cancer 8(4):796–802.<796::AID-CNCR2820080425>3.0.CO;2-Y Google Scholar
  32. 32.
    Matsubara J, Ono M, Negishi A, Ueno H, Okusaka T, Furuse J, Furuta K, Sugiyama E, Saito Y, Kaniwa N, Sawada J, Honda K, Sakuma T, Chiba T, Saijo N, Hirohashi S, Yamada T (2009) Identification of a predictive biomarker for hematologic toxicities of gemcitabine. J Clin Oncol 27(13):2261–2268. Google Scholar
  33. 33.
    Kundu JK, Surh YJ (2012) Emerging avenues linking inflammation and cancer. Free Radic Biol Med 52(9):2013–2037. Google Scholar
  34. 34.
    Neumcke I, Schneider B, Fandrey J, Pagel H (1999) Effects of pro- and antioxidative compounds on renal production of erythropoietin. Endocrinology 140(2):641–645. Google Scholar
  35. 35.
    Spivak JL, Gascon P, Ludwig H (2009) Anemia management in oncology and hematology. Oncologist 14(Suppl 1):43–56. Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Student Research Committee, Urology and Nephrology Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Radiation Oncology, Shohada-e-Tajrish Medical CenterShahid Beheshti University of Medical SciencesTehranIran

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