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Trifluridine/Tipiracil and Bevacizumab in Adults with Refractory Metastatic Colorectal Cancer

Gabriel Valagni, Nkafu Bechem Ndemazie, Tiago Biachi de Castria

Trifluridine/tipiracil (FTD/TPI) is a novel oral formulation of two drugs with promising results in the treatment of metastatic colorectal cancer (mCRC).1 Trifluridine is a thymidine-based nucleoside analogue that, after intracellular phosphorylation, gets incorporated into DNA, causing DNA dysfunction.2 It was first identified by Callahan et al. in 1996 as an active impurity in the herbicide trifluralin, which […]

touchREVIEWS in Oncology & Haematology. 2024;20(2):Online ahead of journal publication

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The Role of Complete Blood Cell Count in Prognosis—Watch this Space!

Nicole M Rochet, Svetomir N Markovic, Luis F Porrata
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Published Online: May 25th 2012 Oncology & Hematology Review, 2012;8(1):76–82 DOI: https://doi.org/10.17925/OHR.2012.08.1.76
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1

Abstract

Overview

Prognostic factors in cancer patients provide information about possible clinical outcomes and help classify patients into different risk groups. Treatment and clinical management decisions are often challenging, thus the availability of reliable and accessible prognostic markers is vital when designing treatment plans and discussing them with patients. This article discusses the prognostic value of the complete blood cell count components (i.e., white blood cell count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, hemoglobin level, and platelet count) in regard to clinical outcomes in patients with malignant disorders.

Keywords

Complete blood cell count, white blood cell count, hemoglobin level, platelet count, neutrophil count, lymphocyte count, monocyte count, survival, cancer, prognosis

2

Article

Prognostic factors of clinical outcomes in patients with cancer are a useful tool in the practice of medicine, especially in the fields of oncology and malignant hematology. A good prognostic factor should reflect the biology of its targeted disease, be inexpensive, reliable, reproducible, and standardized. Furthermore, a universal prognostic factor that can predict survival regardless of the type of cancer will help to simplify the management of cancer patients. In this article, we describe the undermined universal prognostic value of a low-cost, standardized, reliable, and reproducible prognostic factor in cancer: the complete blood cell (CBC) count and its components.

White Blood Cell Count

The absolute white blood cell (WBC) count obtained from the CBC count has been historically used as a marker of infection and inflammation. It is a widely available tool for clinicians to identify the presence of infection and monitor the patient’s response to treatment, such as antibiotics. Nonetheless, the role of the WBC count has gone beyond the assessment of infectious processes and it has become an important prognostic measurement of outcomes in cancer treatment. The inflammatory process that takes place during cancer development and progression are, in part, reflected in abnormalities of the WBC count.
In hematologic malignancies, the WBC count is a prognostic factor for clinical outcomes included in international prognostic systems. For example, in advanced Hodgkin’s lymphoma (HL), the International Prognostic Score (IPS) alerts cancer specialists of worse clinical outcomes in patients presenting with a WBC count ≥15,000/mm3.1 Another international prognostic system that associates a higher WBC count count with adverse clinical outcomes is the Mantle Cell Lymphoma International Prognostic Index (MIPI). The MIPI has been validated in several population-based cohorts, confirming that a high WBC count is a negative predictor of survival.2,3
In addition to hematologic malignancies, the WBC count has been reported to be of prognostic value in solid tumors. Pre-treatment leukocytosis, defined as a WBC count >10,000/μl, has been shown to be an independent prognostic factor of survival in cervical cancer patients.4 In non-small cell lung cancer (NSCLC), the prognostic importance of the WBC count has been studied in patients before the initiation of systemic treatment and as a pre-operative measure, in both cases showing that an elevated WBC count is a significant predictor of overall survival (OS) and time to progression of disease.5–7 Mandrekar et al.5 developed a survival prediction model for newly diagnosed advanced-stage NSCLC that incorporates WBC count as one of the variables. Additionally, patients with metastatic melanoma who exhibit a high pre-treatment leukocyte count (>10 x 109/l) have poor clinical outcomes following biochemotherapy in both OS (hazard ratio [HR]=1.7; p=0.0005) and progression-free survival (PFS) (HR=1.5; p=0.008).8
Interestingly, 143,748 post-menopausal women were studied, as part of the Women Health Initiative, to determine the association of WBC count with the incidence of cancer and cancer mortality. The study concluded that within this population, women with higher WBC counts have an increased risk of developing invasive breast, colorectal, endometrial, and lung cancer, as well as a higher risk of overall mortality in breast and lung cancer.9 As a biomarker of inflammation, the WBC count is a simple test to roughly assess inflammation in patients with cancer.

Absolute Neutrophil Count

Many of the cells and mediators involved in the development of the systemic inflammatory response are also found in the microenvironment of tumors; it is believed that these factors support tumor growth and progression, affecting host antitumor activity, which underlies the importance of identifying markers associated with cancer-inflammatory response.10,11 Neutrophils are central to this inflammatory response. The prognostic significance of the absolute neutrophil count (ANC) has been extensively studied, with evidence to suggest that blood neutrophils provide significant information when monitoring cancer progression, anticipating possible complications and assessing patient’s tolerance to therapy.
The association between malignancies and inflammation has been extensively studied in cervical cancer, in part due to evidence linking this neoplasm with papillomavirus infection. One study analyzed the number and functions of neutrophils in healthy controls, patients with pre- or micro-invasive stages, and patients with invasive cervical cancer, reporting an association between neutrophilia and an advanced stage of cervical cancer as well as impaired neutrophil migration in the invasive cancer group.12 These results suggest that the defective neutrophils are associated with tumor development and impaired host immune response. Another study in cervical cancer patients proposed a new prognostic marker multiplying the pre-treatment neutrophil and monocyte counts, and reported that those with an elevated value had a poor outcome.13 A different study of 338 patients with stage III and IV NSCLC reported that pre-treatment elevated neutrophil counts (≥4,500 mm-3) were significantly associated with decreased OS (p=0.0008) and PFS (p=0.024).14 Furthermore, the role of the immune system in patients receiving immunotherapy has been assessed using the peripheral neutrophil count as a predictor of treatment response and survival in metastatic renal cell carcinoma and stage IV melanoma, consistently reporting that a high neutrophil count is an independent prognostic factor for short OS; however, these studies used different cutoff values to divide patients into high versus low neutrophil groups.8,15,16
It has been repeatedly shown in many types of malignancies that the neutrophil:lymphocyte ratio (NLR) is a prognostic marker of survival. In a study of patients with colorectal cancer (some who received palliative care only, others surgical resection, and another group that underwent surgical palliative care), an elevated pre-treatment NLR was associated with the worst OS, but this was not independent of stage.17 Similarly, other studies confirmed that an elevated NLR prior to treatment is a useful predictor of survival in breast,18 ovarian,19 gastric,20–22 colon,23 lung,24 and pancreatic cancer25–27 (in these studies the cutoff value of NLR ranged from 2.5 to 5.0). In hepatocellular carcinoma, the prognostic significance of the NLR has not only been evaluated at diagnosis and pre-operatively, but also as a marker of tumor recurrence after liver transplantation.28–31 Interestingly, a study that evaluated NLR patients with unresectable hepatocellular carcinoma who were treated with transarterial chemoembolization reported that patients with a NLR ≥3.3 before treatment had a worse OS (median survival of eight months versus 12 months for patients with a NLR <3.3; p=0.001). However, an increased NLR after treatment was associated with better outcome (p=0.006), suggesting that, in these patients, transarterial chemoembolization triggered an antitumor immune response through the mobilization of lymphoid and myeloid cells.32
It has also been reported that the NLR may provide useful information for prognostication in patients undergoing systemic cancer therapy. In a retrospective study of patients with malignant mesothelioma treated with systemic therapy, an NLR <5 was associated with a 10-month longer survival than an NLR ≥5 (16.7 versus 6.6 months); the study confirmed that NLR is an independent predictor of poor survival regardless of whether systemic therapy was the initial or subsequent treatment.33 Similar results were obtained in a study that evaluated the prognostic significance of NLR in patients with advanced colorectal cancer treated with chemotherapy. In this study, an NLR ≤5 and combination chemotherapy were associated with improved PFS and OS.34 Also, normalization of the NLR after one cycle of chemotherapy was a strong predictor of benefit from treatment, resulting in improved PFS. Moreover, the prognostic role of NLR was also validated in patients with pancreatic and colorectal liver metastasis treated with chemotherapy (the cutoff value for NLR used in these studies was 5).35,36
The neutrophil count has also been studied in hematologic malignancies, proving to be as strong a prognostic tool as in solid tumors. The International Prognostic Scoring System (IPSS), developed to evaluate outcomes in myelodysplastic syndromes, incorporated cytopenias as one of their prognostic parameters, considering patients with neutropenia as a negative factor for disease outcome.37,38 Recently, the NLR at diagnosis was shown to be a prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL) treated with combination chemotherapy. NLR ≥3.5 was associated with worse clinical outcomes (including reduced PFS and OS) when compared with patients with NLR <3.5. Another significant finding of this study was the association between B-symptoms (fever and night sweats) and a high NLR at diagnosis.39 Clearly, the neutrophil count alone or the NLR provide inexpensive information regarding solid and hematologic malignancy outcomes that may guide treatment decisions.

Absolute Lymphocyte Count

The absolute lymphocyte count (ALC) has been studied in hematologic and solid malignancies as a marker of host antitumor immunity. Its prognostic significance has been evaluated during different clinical stages of cancer, including at diagnosis, at different phases of chemotherapy or radiation treatment, and after autologous stem-cell transplantation (ASCT). ALC is proven to be an independent prognostic factor for survival, independent of cancer type, and it is included in several validated prognostic scores, such as the IPS in advanced HL.1

Absolute Lymphocyte Count at Diagnosis

ALC at diagnosis can be considered a biomarker of immune status to the presence of a malignancy. Several studies have confirmed the utility of ALC in predicting survival in patients with lymphoma. One of the first studies to assess the prognostic role of ALC at the time of diagnosis involved 228 patients with follicular lymphomas and it reported that the OS was significantly better for patients with an ALC >1 x 109/l compared with an ALC <1 x 109/l at diagnosis.40 Decreased lymphocyte count at the time of diagnosis has also been reported to correlate with reduced OS in classical HL41–43 and in DLBCL patients receiving chemotherapy.44 In DLBCL, a low ALC has been identified as an adverse prognostic factor associated to inferior OS and confirmed to add additional prognostic information when compared to the International Prognostic Index (IPI), which is the standard tool used to predict outcomes in DLBCL.42,43 Superior clinical outcome has also been reported in DLBCL patients who have an ALC >1 x 109/l at the time of first relapse.45
The status of the immune system at diagnosis has also been studied in patients with multiple myeloma (MM) through the analysis of the peripheral ALC. In a cohort of 537 patients with newly diagnosed MM, those with an ALC >1.4 x 109/l experienced a higher OS (65 months) when compared with patients with an ALC <1.4 x 109/l (26 months).46 Similar results were reported using the ALC as a prognostic marker in myelodysplastic syndromes (ALC >1.2 x 109/l, median OS of 26.6 months versus ALC <1.2 x 109/l, median OS of 18.5 months; p<0.001).47

Absolute Lymphocyte Count Pre-Treatment and During Treatment

Prognostic markers for cancer patients who are receiving treatment are valuable tools for clinicians to make informed decisions and a useful way to stratify patients into groups who would likely benefit from a particular intervention. A recent study validated a prognostic score that included the lymphocyte count to asses survival in patients undergoing chemotherapy for advanced or metastatic cancer after first-line treatment.48 The majority of patients included in this prospective study had primary breast, lung, or ovarian cancer and treatment after inclusion included chemotherapy, immunotherapy, radiotherapy, and supportive care. An ALC <700/μl was reported as an independent predictor of decreased survival in this cohort of metastatic patients.48
The role of ALC recovery after induction chemotherapy has been study in patients diagnosed with acute myelogenous leukemia.49 The authors reported that in a cohort of 103 patients, subjects with an ALC ≥500 cells/μl at all time points (days 15, 21, and 28 after induction chemotherapy and before first consolidation chemotherapy) had a superior OS and leukemia-free survival. Another study showed that patients with DLBCL with confirmed relapse at follow-up had a lower ALC compared with those without evidence of relapse after receiving immunotherapy (R-CHOP).50 Furthermore, the antitumor status of the host immune system evaluated through the peripheral ALC has also been assessed in patients receiving radioimmunotherapy,51 treatment with cytotoxic T-lymphocyte antigen,52 and chemoradiation53 in both hematologic and solid malignancies, with a general consensus that a higher ALC is associated with better response to treatment and superior OS.
The above-mentioned studies suggest that lymphocytes have a role in the anticancer immunosurveillance of the host defense mechanism during chemotherapy, radiotherapy, and immunotherapy. Cancer clinicians should pay special attention to this CBC count parameter when making treatment decisions and should carefully monitor the host’s immune status as a way to anticipate possible outcomes.

Absolute Lymphocyte Count in Autologous Stem Cell Transplant

Numerous studies have focused their attention on immune reconstitution after autologous hematopoietic stem cell transplantation (AHSCT) as treatment for malignant diseases. Early ALC recovery after AHSCT is considered a marker of post-transplantation immune recovery and is associated with prolonged survival. One of the first studies to assess the prognostic significance of ALC recovery after ASCT consisted of patients with MM and non-Hodgkin’s lymphoma (NHL), using an ALC cutoff value of 500 cells/μl on Day 15 after transplant.54 The data analyzed in this study showed that ALC ≥500 cells/μl on Day 15 after ASCT is an independent prognostic factor of OS and PFS (in MM, the median OS for patients with an ALC ≥500 cells/μl was 33 months versus 12 months for patients with an ALC <500 cells/μl [p<0.0001]; in NHL, the median OS for patients with an ALC ≥500 cells/μl was not reached versus six months for patients with an ALC <500 cells/μl [p<0.001]). Subsequently, two different studies in NHL and MM patients provided evidence in favor of the prognostic importance of ALC after ASCT by establishing that ALC on Day 15 is directly dependent on dose-infused autograft lymphocytes (r=0.71 for NHL; r=0.83 for MM) and influences survival.55,56
Over the years, many studies have validated the prognostic significance of early ALC recovery post-ASCT as an indicator of survival in multiple malignant hematologic conditions,57–60 metastatic breast cancer,61,62 and primary systemic amyloidosis,63 concluding that a higher ALC on Day 15 post-transplant is associated with significantly improved clinical outcomes. Furthermore, new-onset lymphopenia (as measured by ALC) during routine follow-up after ASCT was identified as a simple marker to assess relapse in patients with DLBCL (patients with an ALC <1.0 x 109/l had a greater cumulative incidence of relapse).64

Absolute Monocyte Count

It has been postulated that monocytes promote tumor progression and support host antitumor immunity. Moreover, an increased monocyte count in the peripheral blood is considered a predictive factor of poor prognosis in cancer patients. Sasaki and colleagues65,66 studied the pre-operative absolute monocyte count (AMC) in patients who had had liver resection due to hepatocellular carcinoma, as well as in patients who underwent hepatic surgery due to colorectal metastasis. They reported that a pre-operative AMC of ≥300/mm3 was an independent prognostic indicator of tumor recurrence in cirrhotic patients with hepatocellular carcinoma. In the study of 97 patients with colorectal liver metastasis, univariate analysis showed that patients with a pre-operative monocyte count >300/mm3 had a worse five-year cancer related survival when compared with patients with a monocyte count ≤300/mm3 (p=0.04), but disease-free survival rates did not differ between both groups.66 Elevated pre-operative monocyte counts in a multivariate analysis were found to be an independent prognostic factor for cancer-related survival.
Another study of patients with stage IV melanoma treated with interleukin-2-based immunotherapy identified elevated monocyte counts as a negative prognostic factor (HR=1.7; p<0.001).16 A high peripheral AMC (alone or combined with neutrophil count) has also been associated with adverse outcomes in cervical and ovarian cancer.13,67
The peripheral blood monocyte count has also been examined in hematologic malignancies, such as leukemia and lymphoma. In patients with DLBCL, an elevated AMC ≥630/μl at time of initial diagnosis was associated with inferior PFS and OS.43 Furthermore, this study combined the ALC and monocyte count at diagnosis to evaluate the AMC:ALC ratio as a prognostic score and this new score was able to identify low-, intermediate-, and high risk patients. In addition, they were able to show that the AMC:ALC ratio provides additional prognostic information when compared with the IPI. Nonetheless, in classical HL, the peripheral blood lymphocyte:monocyte ratio at diagnosis was reported as a strong predictor of OS, PFS, and time to progression. This study was not only able to evaluate the prognostic significance of the combined lymphocyte:monocyte ratio, but also reported that an AMC ≥900 cells/μl at diagnosis is an indicator of inferior survival and worse outcome.41
The above-mentioned studies provide evidence that monocytes are immunologically relevant host factors that can be routinely assessed through the CBC count to monitor patients’ response to treatment and identify high-risk patients who are more likely to have adverse outcomes.

Hemoglobin Concentration

Anemia is a common morbidity encountered in cancer patients and, as a consequence, anemic patients suffer from shortness of breath, fatigue, and decreased energy, among other symptoms. Anemia can be a due to the malignancy itself or be a direct consequence of treatment, such as radiotherapy or chemotherapy. Therefore, the hemoglobin concentration in peripheral blood has also been studied as a prognostic factor in malignant disorders.
The role of hemoglobin levels in clinical outcomes has been extensively examined in gynecologic malignancies, such as cervical, ovarian, and endometrial cancer. In 1989, a retrospective study of 386 patients with advanced cervical carcinoma treated with radiotherapy established that anemic patients had a higher risk of treatment failure during treatment.68 Subsequently, various studies have established an association between hemoglobin levels and survival in cervical carcinoma.69–72 A retrospective review of 494 women with locally advanced cervical cancer treated with cisplatin and radiotherapy reported that low hemoglobin levels in the last part of treatment were predictive of disease recurrence and survival, whereas patients with a hemoglobin level <10.0 g/dl had a significantly lower PFS.72 This study also reported that patients with large tumor size and higher stage of disease had lower hemoglobin levels at baseline, suggesting that hemoglobin is a tumor-related factor. Other cervical cancer studies have reported a relationship between baseline hemoglobin level and better response to chemotherapy,69 as well as longer disease-free survival and OS in patients treated with radiotherapy who had a baseline hemoglobin level ≥12 g/dl.71
Similar results have been described for other solid malignancies, including ovarian,73–76 endometrial,77–79 esophageal,80–84 and lung cancer,5,7,85–90 reporting that a low hemoglobin count is an indicator of poor prognosis. The above-mentioned studies suggest that close attention should be paid to anemia before and during treatment, with the goal of maintaining adequate hemoglobin levels and, as a consequence, ideally improving cancer outcomes and quality of life.

Platelet Count

Angiogenesis is considered an essential step for tumor growth, progression, and metastasis. Vascular endothelial growth factor (VEGF) is a known potent stimulator of angiogenesis and, in addition, it has been demonstrated that platelets are a source of VEGF.91 Hence, researchers have reported a strong positive correlation between VEGF serum concentration and platelet counts in cancer patients, as well as a worse prognosis in those patients with higher concentrations of serum VEGF per platelet count.92,93
The prognostic significance of the platelet count has been studied in several malignancies, yielding important information about clinical outcomes. Thrombocytosis has been associated with unfavorable prognosis or advanced disease in gynecological cancers,74,94–97 esophageal carcinoma,98 gastric cancer,99 and lung cancer.7,100–103 Most of these studies used different cutoff values to define thrombocytosis (ranging from 293 x 109/l to 400 x 109/l); however, a high platelet count was always identified as a negative prognostic factor. In surgically resected NSCLC, an increased pre-operative platelet count has consistently been associated with statistically significant reduced survival when compared with patients without thrombocytosis.7,100,103
The peripheral blood platelet count has also been investigated in patients with malignant mesothelioma. In 1989, Ruffie et al.104 published one of the first studies to identify a platelet count ≥400,000/μl as a significant prognostic indicator of decreased survival in mesothelioma (p=0.001 in a multivariate analysis; n=328). These results were validated in subsequent studies that confirmed that a high platelet count is an indicator of poor clinical outcome.105–107
Recent studies have examined the prognostic role of the platelet count as an additional risk factor that should be added to the IPPS108 and the Dynamic International Prognostic Scoring System (DIPSS)109 for primary myelofibrosis (PMF). In these studies, researchers showed that a platelet count <100 x 109/l is an independent prognostic factor of survival in PMF patients, with a shorter median survival when this factor was added to the above-mentioned prognostic scores. In the DIPSS study, a platelet count <100 x 109/l was associated with inferior survival in both the training set (n=428) and the test set (n=365).109 In addition, all 793 patients were assessed for leukemic transformation and the analysis identified a platelet count <100 x 109/l as an independent predictor of leukemia-free survival. Hence, it is likely that future prognostic models in PMF will include the platelet count as an important predictive parameter of clinical outcomes.

Conclusion

It is evident that components of the CBC count can provide valuable prognostic information in solid tumors and hematologic malignancies (summarized in Table 1) that are not only limited to survival predictions or assessment of disease progression, but also are important tools when evaluating response to treatment. Despite numerous studies to evaluate the prognostic significance of these factors and their potential clinical applications, in many cancers, these markers are still not routinely used in clinical practice as a tool to monitor disease progression or response to treatment. One reason is that most of the published studies were retrospective in nature. Additionally, many of them used different cutoff values for the prognostic analysis, complicating their interpretation. Thus, true assessment of the utility of the CBC count as an inexpensive, established, and globally accessible prognostic factor in many malignancies requires careful prospective studies. It is likely that future prospective studies examining the biology behind the prognostic value of the different components of the CBC count would later yield significant therapeutic progress and a thorough understanding of disease pathogenesis. ■

2

References

  1. Hasenclever D, Diehl V, A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease, N Engl J Med, 1998;339(21):1506–14.
  2. Smith SD, Hsi E, Bolwell B, et al., Validation of the Mantle Cell Lymphoma International Prognostic Index: a single-center retrospective analysis, Am J Hematol, 2010;85(6):454–6.
  3. Van de Schans SA, Janssen-Heijnen ML, Nijziel MR, et al., Validation, revision and extension of the Mantle Cell Lymphoma International Prognostic Index in a population-based setting, Haematologica, 2010;95(9):1503–9.
  4. Mabuchi S, Matsumoto Y, Isohashi F, et al., Pre-treatment leukocytosis is an indicator of poor prognosis in patients with cervical cancer, Gynecol Oncol, 2011;122(1):25–32.
  5. Mandrekar SJ, Schild SE, Hillman SL, et al., A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials, Cancer, 2006;107(4):781–92.
  6. Tibaldi C, Vasile E, Bernardini I, et al., Baseline elevated leukocyte count in peripheral blood is associated with poor survival in patients with advanced non-small cell lung cancer: a prognostic model, J Cancer Res Clin Oncol, 2008;134(10):1143–9.
  7. Tomita M, Shimizu T, Hara M, et al., Preoperative leukocytosis, anemia and thrombocytosis are associated with poor survival in non-small cell lung cancer, Anticancer Res, 2009;29(7):2687–90.
  8. Schmidt H, Suciu S, Punt CJ, et al., Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial, J Clin Oncol, 2007;25(12):1562–9.
  9. Margolis KL, Rodabough RJ, Thomson CA, et al., Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women, Arch Intern Med, 2007;167(17):1837–44.
  10. Balkwill F, Mantovani A, Inflammation and cancer: back to Virchow?, Lancet, 2001;357(9255):539–45.
  11. Moore MM, Chua W, Charles KA, Clarke SJ, Inflammation and cancer: causes and consequences, Clin Pharmacol Ther, 2010;87(4):504–8.
  12. Fernandes PC Jr, Garcia CB, Micheli DC, et al., Circulating neutrophils may play a role in the host response in cervical cancer, Int J Gynecol Cancer, 2007;17(5):1068–74.
  13. Cho H, Kim JH, Multiplication of neutrophil and monocyte counts (MNM) as an easily obtainable tumour marker for cervical cancer, Biomarkers, 2009;14(3):161–70.
  14. Teramukai S, Kitano T, Kishida Y, et al., Pre-treatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03, Eur J Cancer, 2009;45(11):1950–8.
  15. Atzpodien J, Reitz M, Peripheral blood neutrophils as independent immunologic predictor of response and longterm survival upon immunotherapy in metastatic renal-cell carcinoma, Cancer Biother Radiopharm, 2008;23(1):129–34.
  16. Schmidt H, Bastholt L, Geertsen P, et al., Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model, Br J Cancer, 2005;93(3):273–8.
  17. Walsh SR, Cook EJ, Goulder F, et al., Neutrophil–lymphocyte ratio as a prognostic factor in colorectal cancer, J Surg Oncol, 2005;91(3):181–4.
  18. Azab B, Bhatt VR, Phookan J, et al., Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients, Ann Surg Oncol, 2011;1:217–24.
  19. Cho H, Hur HW, Kim SW, et al., Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment, Cancer Immunol Immunother, 2009;58(1):15–23.
  20. Aliustaoglu M, Bilici A, Ustaalioglu BB, et al., The effect of peripheral blood values on prognosis of patients with locally advanced gastric cancer before treatment, Med Oncol, 2010;27(4):1060–5.
  21. Ubukata H, Motohashi G, Tabuchi T, et al., Evaluations of interferon-gamma/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients, J Surg Oncol, 2010;102(7):742–7.
  22. Yamanaka T, Matsumoto S, Teramukai S, et al., The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer, Oncology, 2007;73(3–4):215–20.
  23. Ding PR, An X, Zhang RX, et al., Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence following curative resection for stage IIA colon cancer, Int J Colorectal Dis, 2010;25(12):1427–33.
  24. Sarraf KM, Belcher E, Raevsky E,et al., Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer, J Thorac Cardiovasc Surg, 2009;137(2):425–8.
  25. Aliustaoglu M, Bilici A, Seker M, et al., The association of pre-treatment peripheral blood markers with survival in patients with pancreatic cancer, Hepatogastroenterology, 2010;57(99–100):640–5.
  26. Bhatti I, Peacock O, Lloyd G, et al., Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil–lymphocyte versus platelet–lymphocyte ratio, Am J Surg, 2010;200(2):197–203.
  27. Garcea G, Ladwa N, Neal CP, et al., Preoperative neutrophil-tolymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma, World J Surg, 2011;35(4):868–72.
  28. Bertuzzo VR, Cescon M, Ravaioli M, et al., Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers, Transplantation, 2011;91(11):1279–85.
  29. Gomez D, Farid S, Malik HZ, et al., Preoperative neutrophil-tolymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma, World J Surg, 2008;32(8):1757–62.
  30. Guo ZX, Wei W, Zhong C et al., Correlation of preoperative neutrophil-to-lymphocyte ratio to prognosis of young patients with hepatocellular carcinoma, Ai Zheng, 2009;28(11):1203–8.
  31. Halazun KJ, Hardy MA, Rana AA, et al., Negative impact of neutrophil–lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma, Ann Surg, 2009;250(1):141–51.
  32. Huang ZL, Luo J, Chen MS, et al., Blood neutrophil-tolymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization, J Vasc Interv Radiol, 2011;22(5):702–9.
  33. Kao SC, Pavlakis N, Harvie R, et al., High blood neutrophil-tolymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy, Clin Cancer Res, 2010;16(23):5805–13.
  34. Chua W, Charles KA, Baracos VE, Clarke SJ, Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer, Br J Cancer, 2011;104(8):1288–95.
  35. An X, Ding PR, Li YH, et al., Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer, Biomarkers, 2010;15(6):516–22.
  36. Kishi Y, Kopetz S, Chun YS, et al., Blood neutrophil-tolymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy, Ann Surg Oncol, 2009;16(3):614–22.
  37. Sanz GF, Sanz MA, Greenberg PL, Prognostic factors and scoring systems in myelodysplastic syndromes, Haematologica, 1998;83(4):358–68.
  38. Greenberg P, Cox C, LeBeau MM, et al., International scoring system for evaluating prognosis in myelodysplastic syndromes, Blood, 1997;89(6):2079–88.
  39. Porrata LF, Ristow K, Habermann T, et al., Predicting survival for diffuse large B-cell lymphoma patients using baseline neutrophil/lymphocyte ratio, Am J Hematol, 2010;85(11):896–9.
  40. Siddiqui M, Ristow K, Markovic SN, et al., Absolute lymphocyte count predicts overall survival in follicular lymphomas, Br J Haematol, 2006;134(6):596–601.
  41. Porrata LF, Ristow K, Colgan JP, et al., Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in classical Hodgkin’s lymphoma, Haematologica, 2012;97(2):262–9.
  42. Talaulikar D, Choudhury A, Shadbolt B, Brown M, Lymphocytopenia as a prognostic marker for diffuse large B cell lymphomas, Leuk Lymphoma, 2008;49(5):959–64.
  43. Wilcox RA, Ristow K, Habermann TM, et al., The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma, Leukemia, 2011;25(9):1502–9.
  44. Kim DH, Baek JH, Chae YS, et al., Absolute lymphocyte counts predicts response to chemotherapy and survival in diffuse large B-cell lymphoma, Leukemia, 2007;21(10):2227–30.
  45. Porrata LF, Ristow K, Habermann TM, et al., Absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large B-cell lymphoma, Am J Hematol, 2009;84(2):93–7.
  46. Ege H, Gertz MA, Markovic SN, et al., Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective study, Br J Haematol, 2008;141(6):792–8.
  47. Jacobs NL, Holtan SG, Porrata LF, et al., Host immunity affects survival in myelodysplastic syndromes: independent prognostic value of the absolute lymphocyte count, Am J Hematol, 2010;85(3):160–3.
  48. Trédan O, Ray-Coquard I, Chvetzoff G, et al., Validation of prognostic scores for survival in cancer patients beyond first-line therapy, BMC Cancer, 2011;11:95.
  49. Behl D, Porrata LF, Markovic SN, et al., Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia, Leukemia, 2006;20(1):29–34.
  50. Porrata LF, Rsitow K, Inwards DJ, et al., Lymphopenia assessed during routine follow-up after immunochemotherapy (R-CHOP) is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma, Leukemia, 2010;24(7):1343–9.
  51. Porrata LF, Ristow K, Witzig TE, et al., Absolute lymphocyte count predicts therapeutic efficacy and survival at the time of radioimmunotherapy in patients with relapsed follicular lymphomas, Leukemia, 2007;21(12):2554–6.
  52. Ku GY, Yuan J, Page DB, et al., Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival, Cancer, 2010;116(7):1767–75.
  53. Choi CH, Kang H, Kim WY, et al., Prognostic value of baseline lymphocyte count in cervical carcinoma treated with concurrent chemoradiation, Int J Radiat Oncol Biol Phys, 2008;71(1):199–204.
  54. Porrata LF, Gertz MA, Inwards DJ, et al., Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma, Blood, 2001;98(3):579–85.
  55. Porrata LF, Litzow MR, Inwards DJ, et al., Infused peripheral blood autograft absolute lymphocyte count correlates with day 15 absolute lymphocyte count and clinical outcome after autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin’s lymphoma, Bone Marrow Transplant, 2004;33(3):291–8.
  56. Porrata LF, Gertz MA, Geyer SM, et al., The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma, Leukemia, 2004;18(6):1085–92.
  57. Porrata LF, Litzow MR, Tefferi A, et al., Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia, Leukemia, 2002;16(7):1311–8.
  58. Porrata LF, Inwards DJ, Micallef IN, et al., Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin’s disease, Br J Haematol, 2002;117(3):629–33.
  59. Joao C, Porrata LF, Inwards DJ, et al., Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma, Bone Marrow Transplant, 2006;37(9):865–71.
  60. Porrata LF, Inwards DJ, Ansell SM, et al., Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study, Biol Blood Marrow Transplant, 2008;14(7):807–16.
  61. Porrata LF, Ingle JN, Litzow MR, et al., Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer, Bone Marrow Transplant, 2001;28(9):865–71.
  62. Nieto Y, Shpall EJ, McNiece IK, et al., Prognostic analysis of early lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with an autologous hematopoietic progenitor cell transplant, Clin Cancer Res, 2004;10(15):5076–86.
  63. Porrata LF, Gertz MA, Litzow MR, et al., Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis, Clin Cancer Res, 2005;11(3):1210–8.
  64. Porrata LF, Inwards DJ, Ansell SM, et al., New-onset lymphopenia assessed during routine follow-up is a risk factor for relapse postautologous peripheral blood hematopoietic stem cell transplantation in patients with diffuse large B-cell lymphoma, Biol Blood Marrow Transplant, 2010;16(3):376–83.
  65. Sasaki A, Iwashita Y, Shibata K, et al., Prognostic value of preoperative peripheral blood monocyte count in patients with hepatocellular carcinoma, Surgery, 2006;139(6):755–64.
  66. Sasaki A, Kai S, Endo Y, et al., Prognostic value of preoperative peripheral blood monocyte count in patients with colorectal liver metastasis after liver resection, J Gastrointest Surg, 2007;11(5):596–602.
  67. Bishara S, Griffin M, Cargill A, et al., Pre-treatment white blood cell subtypes as prognostic indicators in ovarian cancer, Eur J Obstet Gynecol Reprod Biol, 2008;138(1):71–5.
  68. Girinski T, Pejovic-Lenfant MH, Bourhis J, et al., Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients, Int J Radiat Oncol Biol Phys, 1989;16(1):37–42.
  69. Fuso L, Mazzola S, Marocco F, et al., Pretreatment serum hemoglobin level as a predictive factor of response to neoadjuvant chemotherapy in patients with locally advanced squamous cervical carcinoma: a preliminary report, Gynecol Oncol, 2005;99(3, Suppl. 1):S187–91.
  70. Obermair A, Cheuk R, Horwood K, et al., Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: effect on progression-free survival, Int J Gynecol Cancer, 2003;13(5):633–9.
  71. Serkies K, Badzio A, Jassem J, Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy, Acta Oncol, 2006;45(6):695–701.
  72. Winter WE 3rd, Maxwell GL, Tian C, et al., Association of hemoglobin level with survival in cervical carcinoma patients treated with concurrent cisplatin and radiotherapy: a Gynecologic Oncology Group Study, Gynecol Oncol, 2004;94(2):495–501.
  73. Gadducci A, Cosio S, Fanucchi A, et al., Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?, Eur J Gynaecol Oncol, 2003;24(5):405–10.
  74. Munstedt K, Kovacic M, Zygmunt M, Von Georgi R, Impact of hemoglobin levels before and during chemotherapy on survival of patients with ovarian cancer, Int J Oncol, 2003;23(3):837–43.
  75. Obermair A, Handisurya A, Kaider A, et al., The relationship of pretreatment serum hemoglobin level to the survival of epithelial ovarian carcinoma patients: a prospective review, Cancer, 1998;83(4):726–31.
  76. Obermair A, Petru E, Windbichler G, et al., Significance of pretreatment serum hemoglobin and survival in epithelial ovarian cancer, Oncol Rep, 2000;7(3):639–44.
  77. Metindir J, Bilir Dilek G, Preoperative hemoglobin and platelet count and poor prognostic factors in patients with endometrial carcinoma, J Cancer Res Clin Oncol, 2009;135(1):125–9.
  78. Munstedt K, Volzing M, Von Georgi R, Hemoglobin levels during radiation therapy and their influence on local control and survival of patients with endometrial carcinoma, Oncol Rep, 2004;11(3):711–7.
  79. Tamussino KF, Gucer F, Reich O, et al., Pretreatment hemoglobin, platelet count, and prognosis in endometrial carcinoma, Int J Gynecol Cancer, 2001;11(3):236–40.
  80. Valencia Julve J, Alonso Orduna V, Esco Baron R, et al., Influence of hemoglobin levels on survival after radical treatment of esophageal carcinoma with radiotherapy, Clin Transl Oncol, 2006;8(1):22–30.
  81. Rades D, Lang S, Schild SE, Alberti W, Prognostic value of haemoglobin levels during concurrent radio-chemotherapy in the treatment of oesophageal cancer, Clin Oncol (R Coll Radiol), 2006;18(2):139–44.
  82. Rades D, Schild SE, Bahrehmand R, et al., Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy: the importance of pretreatment hemoglobin levels, Cancer, 2005;103(8):1740–6.
  83. Zhao KL, Liu G, Jiang GL, et al., Association of haemoglobin level with morbidity and mortality of patients with locally advanced oesophageal carcinoma undergoing radiotherapy – a secondary analysis of three consecutive clinical phase III trials, Clin Oncol (R Coll Radiol), 2006;18(8):621–7.
  84. Zenda S, Hironaka S, Boku N, et al., Impact of hemoglobin level on survival in definitive chemoradiotherapy for T4/M1 lymph node esophageal cancer, Dis Esophagus, 2008;21(3):195–200.
  85. Pradier O, Lederer K, Hille A, et al., Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small cell lung cancer: a phase II trial with special reference to the hemoglobin level as prognostic parameter, J Cancer Res Clin Oncol, 2005;131(4):261–9.
  86. Xu C, Gao Y, Li L, et al., Impact of anemia on chemotherapy efficacy and prognosis in patients with advanced non-small cell lung cancer, Zhongguo Fei Ai Za Zhi, 2010;13(10):968–74.
  87. Aoe K, Hiraki A, Maeda T, et al., Serum hemoglobin level determined at the first presentation is a poor prognostic indicator in patients with lung cancer, Intern Med, 2005;44(8):800–4.
  88. Tomita M, Shimizu T, Hara M, et al., Impact of preoperative hemoglobin level on survival of non-small cell lung cancer patients, Anticancer Res, 2008;28(3B):1947–50.
  89. Berardi R, Brunelli A, Tamburrano T, et al., Perioperative anemia and blood transfusions as prognostic factors in patients undergoing resection for non-small cell lung cancers, Lung Cancer, 2005;49(3):371–6.
  90. Langendijk H, de Jong J, Wanders R, et al., The importance of pre-treatment haemoglobin level in inoperable non-small cell lung carcinoma treated with radical radiotherapy, Radiother Oncol, 2003;67(3):321–5.
  91. Banks RE, Forbes MA, Kinsey SE, et al., Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology, Br J Cancer, 1998;77(6):956–64.
  92. Kim SJ, Choi IK, Park KH, et al., Serum vascular endothelial growth factor per platelet count in hepatocellular carcinoma: correlations with clinical parameters and survival, Jpn J Clin Oncol, 2004;34(4):184–90.
  93. O’Byrne KJ, Dobbs N, Propper D, et al., Vascular endothelial growth factor platelet counts, and prognosis in renal cancer, Lancet, 1999;353(9163):1494–5.
  94. Ayhan A, Bozdag G, Taskiran C, et al., The value of preoperative platelet count in the prediction of cervical involvement and poor prognostic variables in patients with endometrial carcinoma, Gynecol Oncol, 2006;103(3):902–5.
  95. Crasta JA, Premlatha TS, Krishnan SM, et al., Significance of preoperative thrombocytosis in epithelial ovarian cancer, Indian J Pathol Microbiol, 2010;53(1):54–6.
  96. Gerestein CG, Eijkemans MJ, de Jong D, et al., The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma, BJOG, 2009;116(3):372–80.
  97. Gungor T, Kanat-Pektas M, Sucak A, Mollamahmutoglu L, The role of thrombocytosis in prognostic evaluation of epithelial ovarian tumors, Arch Gynecol Obstet, 2009; 279(1):53–6.
  98. Shimada H, Oohira G, Okazumi S, et al., Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma, J Am Coll Surg, 2004;198(5):737–41.
  99. Ikeda M, Furukawa H, Imamura H, et al., Poor prognosis associated with thrombocytosis in patients with gastric cancer, Ann Surg Oncol, 2002;9(3):287–91.
  100. Cox G, Walker RA, Andi A, et al., Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer, Lung Cancer, 2000;29(3):169–77.
  101. Gonzalez Barcala FJ, Garcia Prim JM, Moldes Rodriguez M, et al., Platelet count: association with prognosis in lung cancer, Med Oncol, 2010;27(2):357–62.
  102. Pedersen LM, Milman N, Prognostic significance of thrombocytosis in patients with primary lung cancer, Eur Respir J, 1996;9(9):1826–30.
  103. Tomita M, Shimizu T, Hara M, et al., Prognostic impact of thrombocytosis in resectable non-small cell lung cancer, Interact Cardiovasc Thorac Surg, 2008;7(4):613–5.
  104. Ruffie P, Feld R, Minkin S, et al., Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients, J Clin Oncol, 1989;7(8):1157–68.
  105. Borasio P, Berruti A, Bille A, et al., Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients, Eur J Cardiothorac Surg, 2008;33(2):307–13.
  106. Herndon JE, Green MR, Chahinian AP, et al., Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B, Chest, 1998;113(3):723–31.
  107. Steele JP, Klabatsa A, Fennell DA, et al., Prognostic factors in mesothelioma, Lung Cancer, 2005;49(Suppl. 1):S49–52.
  108. Patnaik MM, Caramazza D, Gangat N, et al., Age and platelet count are IPSS-independent prognostic factors in young patients with primary myelofibrosis and complement IPSS in predicting very long or very short survival, Eur J Haematol, 2010;84(2):105–8.
  109. Gangat N, Caramazza D, Vaidya R, et al., DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status, J Clin Oncol, 2011;29(4):392–7.
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The authors have no conflicts of interest to declare.

Correspondence

Luis F Porrata, MD, Assistant Professor, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. E: porrata.luis@mayo.edu

Received

2012-01-03T00:00:00

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