Myelosuppression and Its Consequences in Elderly Patients With Cancer

Myelosuppression and Its Consequences in Elderly Patients With Cancer

ABSTRACT: Cancer is a disease of the elderly, and its incidence and mortality increase with age. The number of persons with cancer is expected to double between 2000 and 2050, from 1.3 million to 2.6 million, with the elderly accounting for most of this increase. Studies have shown that otherwise-healthy older patients treated with chemotherapy of similar intensity obtain benefits comparable to those obtained by younger patients. However, chemotherapy-induced neutropenia and its complications are more likely in older patients; they are also more often hospitalized because of life-threatening infectious complications. Furthermore, most neutropenic episodes in elderly patients occur in the early cycles of chemotherapy. To minimize the occurrence of chemotherapyinduced neutropenia, older patients are often treated with less-aggressive chemotherapy and with dose reductions and delays, which may compromise treatment outcome. The proactive management of myelosuppression is therefore essential in elderly patients. Research to determine the predictors for neutropenia has found that age itself is a significant risk factor. The benefit of treating elderly patients with colony-stimulating factors is well established, with their use beginning in the first cycle of chemotherapy being crucial for minimizing neutropenia and its complications and facilitating the delivery of full-dose chemotherapy. Such prophylaxis should be routinely considered in elderly patients with cancer treated with myelosuppressive chemotherapy.

It has long been recognized that cancer is primarily a disease of the elderly. Approximately 60% of all newly diagnosed malignancies are in persons aged 65 years or older, as are 70% of all deaths due to cancer.[1-3] With few exceptions, those malignancies with the highest incidences-such as lung, breast, and colon cancer- mainly affect elderly persons.[4] As life expectancy in the United States increases and the population ages, a substantial increase in the number of persons with cancer is expected. In fact, the number of persons with cancer is expected to double in the next 50 years, from 1.3 million in 2000 to 2.6 million in 2050.[2] As in younger patients, chemotherapy is the mainstay of treatment in patients 65 years of age and older, and the benefits of treatment include extended survival, maintenance of and improvement in quality of life, and palliation of symptoms.[5] The elderly are more susceptible to certain toxicities of chemotherapy, however; in particular, myelosuppression and lifethreatening neutropenia are more common in elderly patients, emphasizing the need for prophylactic intervention.[ 6] Chemotherapy-Induced Neutropenia in the Elderly The role of age in patients' susceptibility to the neutropenic complications of chemotherapy has been extensively explored. Clinical and experimental studies have suggested an age-related decline in the number of hematopoietic stem cells, as well as of the ability of the bone marrow to react to hematopoietic stress, such as hemorrhage or infection.[7] These findings may in part explain the higher rates of myelosuppression after chemotherapy in the elderly. Studies of the clinical impact of myelosuppression in the elderly have consistently found a higher incidence of severe neutropenia and its complications in older patients. In a study of adjuvant chemotherapy for breast cancer with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil, the rates of grade 3 hematotoxic effects were significantly higher in older patients than in younger patients (9.2% vs 4.5%; P < .001).[8] Another study in early-stage breast cancer found that the incidence and severity of neutropenia were greater and the absolute neutrophil count nadir was deeper in patients older than 65 years.[9] Retrospective analysis of data from a large randomized phase III trial in non- small-cell lung cancer found a significantly higher incidence of leukopenia in men 70 years of age or older.[10] A retrospective study of practice patterns in non-Hodgkin's lymphoma reported that the incidence of febrile neutropenia was 34% in patients aged 65 years or older and 21% in younger patients.[ 11] Not only are neutropenic complications more frequent in the elderly, they are also often more severe, leading to higher rates of hospitalization, longer hospital stays, and higher mortality. The study of practice patterns mentioned above found that the rate of hospitalization for febrile neutropenia in patients aged 65 years or older was nearly double that in younger patients (28% vs 16%) and the duration of the hospitalization was 30% longer.[11] A study of CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy for non-Hodgkin's lymphoma reported that the mean length of stay in hospitalizations for febrile neutropenia was 9.8 days in elderly patients and 7.0 days in younger patients.[12] In a study of chemotherapy for metastatic breast cancer the incidence of life-threatening febrile neutropenia in elderly patients was twice that in younger patients, and the only treatment- related septic deaths were in the elderly patients.[13] In fact, Kuderer et al, after analyzing data from more than 41,000 adult patients with cancer hospitalized for febrile neutropenia, found that age 65 years or older was associated with more than three times higher mortality (6.68% vs 2.00%).[14] Because of their greater susceptibility to myelosuppression, elderly patients are often given lower doses of chemotherapy-these dose reductions are often planned, beginning with the first chemotherapy cycle. A survey of practice patterns in 2,911 patients with non-Hodgkin's lymphoma reported that treatment with chemotherapy was more likely to begin with a planned average relative dose intensity of 80% or less in older patients than in younger patients (28% vs 12%, P < .001).[15] Another survey of practice patterns, in more than 20,000 patients treated with adjuvant chemotherapy for breast cancer, found that two-thirds of patients 65 or older were treated with a dose intensity of less than 85%.[16] Bias against elderly patients may also be manifested in other ways (Table 1). For example, despite the higher incidence of cancer in older patients, they are substantially underrepresented in clinical trials of chemotherapy.[17] Clinical trial protocols frequently exclude patients older than a specified age, owing in part to concerns about the potential for greater toxicity. A review of trials conducted by the Southwest Oncology Group in various malignancies found that only 25% of 16,396 study subjects were 65 or older, even though such patients accounted for 63% of the population with cancer when those studies were conducted.[18] Physician bias may also play a role in excluding elderly patients from clinical trials. A case-matched study in younger and older women with breast cancer found that older women were less likely to be recruited for and enrolled in clinical trials even though they met the eligibility criteria.[19] Elderly patients are also more likely to be treated with less aggressive, and possibly less effective, regimens than younger patients. A number of studies have investigated alternative, non- doxorubicin-containing regimens in elderly patients with non-Hodgkin's lymphoma, and these regimens are associated with poorer clinical outcomes.[ 20-22] A study in patients with aggressive lymphoma found that elderly patients were less likely to be treated with intent for a cure and were less likely to survive for 5 years or longer.[25] A review of treatment practices in non-small-cell lung cancer in the United Kingdom found that diagnosis and treatment were consistently less aggressive in older patients.[26] Published guidelines recommend that elderly patients be treated with chemotherapy, but sometimes they are not. Patients aged 75 years or older with ovarian cancer were found to be significantly less likely than younger patients to be treated with chemotherapy (58.2% vs 86.1%, P = .001).[23] Mahoney et al found that elderly patients with stage III colon cancer were less likely to be treated with chemotherapy after surgery than were younger patients.[24] Such undertreatment may be a primary cause of the poorer outcomes in elderly patients.[27] Indeed, the use of substandard chemotherapy doses and regimens has been shown to contribute to lower overall survival in patients with chemosensitive tumors in several large studies with long followups.[ 20,21,28-32] Otherwise-healthy elderly patients obtain benefits comparable to those obtained by younger patients when they are treated with chemotherapy of similar dose intensity.[1] This has been seen in numerous malignancies, including non-Hodgkin's lymphoma,[ 20] acute myelogenous leukemia,[ 33] early-stage breast cancer,[34] non-small-cell lung cancer,[10,35] and colon cancer[36] (Table 2). Fit elderly patients should therefore be treated as aggressively and with the same curative intent as younger patients. The greater susceptibility to myelosuppression in older patients, however, means that supportive care with colony-stimulating factor (CSF) and erythropoietic agents must be considered. Pharmacologic studies have shown that, despite the decline in hematopoietic reserves with older age, CSF administration is effective in elderly patients. It has been shown to produce the same dose-related increases in peak neutrophil counts in both young and elderly healthy volunteers.[37] Colony-stimulating factor has also been shown to increase the neutrophil counts by the same degree in young and elderly patients with various malignancies treated with myelosuppressive chemotherapy.[38] Managing neutropenia in elderly patients with prophylactic CSF has been assessed in a number of randomized placebo-controlled studies.[ 22,35,36,39-42] In four of these trials, in elderly patients with non- Hodgkin's lymphoma,[22,39-41] CSF started in the first cycle reduced the incidence of grades 3 and 4 neutropenia and of neutropenic infection by 32% to 82% and 32% to 100%, respectively; P < .01 for both.[43] Early CSF use is also associated with shorter hospitalizations for febrile neutropenia in elderly patients with breast cancer,[13] non-Hodgkin's lymphoma,[40] and acute myelogenous leukemia.[33,44,45] In addition, use of CSF in later cycles in patients treated with adjuvant chemotherapy for breast cancer has been shown to increase the proportion of patients in whom the dose intensity of the chemotherapy is maintained above the 85% threshold.[42,46] The use of CSF early in the course of chemotherapy and throughout all cycles makes it possible to deliver standard full-dose, as well as dose-dense, chemotherapy in older patients, with outcomes comparable to those in younger patients.[47-49] Risk Models for Neutropenia Colony-stimulating factor use in the first cycle of chemotherapy is effective in reducing both the incidence and the severity of neutropenia, as well as related complications, but its routine use in all patients treated with chemotherapy is not considered necessary or cost-effective. As discussed by Lyman in this supplement, efforts are under way to determine the characteristics of patients that place them at greater risk for neutropenia and associated complications.[50] The risk models that have been developed so far have found a number of risk factors for chemotherapy-induced neutropenia and neutropenic complications. Advanced age appears to be a general risk factor for chemotherapy-induced neutropenia and its complications in a number of clinical settings. A review of published risk models in which multivariate analysis had been performed analyzed a total of 18 models, including three that had been validated in separate populations.[6] Advanced age was reported to be an independent, significant risk factor in eight of the models and had been validated in at least two of them. In a separate review of the literature on risk factors for chemotherapy-induced neutropenia, nine studies considered the relation between advanced age and the risk of severe neutropenia, eight of which found that older patients were at greater risk and seven of which found that the relation was statistically significant.[51] Because advanced age has been established as a strong risk factor for neutropenic complications, many studies that have evaluated neutropenic events in this patient population have focused on the timing of complications, it being an important consideration in scheduling and coordinating preventive measures, such as prophylactic CSF. It appears that neutropenic complications-including mortality-commonly occur in the early cycles of chemotherapy in older patients. A retrospective analysis of data from 267 consecutive elderly patients with aggressive non-Hodgkin's lymphoma treated with CHOP found that 13% of the patients died of treatment- related causes, with 63% of the deaths occurring in the first cycle of chemotherapy.[52] Eighty-three percent of these deaths were attributed to infection, and 66% of them were in patients with severe neutropenia (Figure 1). A randomized trial that assessed chemotherapy-induced toxicities in 453 elderly patients with non- Hodgkin's lymphoma reported that, depending on the regimen used, 55% to 72% of the neutropenic events occurred in cycle 1 of the chemotherapy.[ 21] In another study, in 577 patients with non-Hodgkin's lymphoma treated with CHOP, 62% of the initial episodes of febrile neutropenia in elderly patients occurred in cycle 1 (Figure 2).[53] A retrospective analysis of data from two clinical trials in patients with metastatic breast cancer treated with doxorubicin and docetaxel (Taxotere) reported that 75% of all febrile neutropenic events occurred in cycle 1.[54] In summary, there is strong evidence that age itself is a general risk factor for severe neutropenia and that neutropenic complications are most likely in cycles 1 and 2 of chemotherapy. Advanced age may also be associated with other patient characteristics that affect that risk. Thus, a more accurate predictor of neutropenia may be the patient's physiologic, rather than chronologic, age. Nevertheless, the fact that advanced age is a significant risk factor-and in the absence of other risk factors to determine which elderly patients are at greatest risk-argues for the use of CSF started in the first cycle of chemotherapy in elderly patients. Such a strategy appears to be most effective in minimizing neutropenic complications and in facilitating the delivery of full-dose chemotherapy. The current guidelines of the American Society of Clinical Oncology (ASCO) for the use of CSF recommend its use in the first cycle of chemotherapy in certain populations of patients who are at higher risk for neutropenic complications. The "special circumstances" in these guidelines include poor performance status, advanced cancer, previous radiation therapy, extensive previous chemotherapy, history of febrile neutropenia, existing neutropenia, and conditions that increase the risks of serious infection.[55] Advanced age has consistently been found in several risk models to be an independent risk factor for severe neutropenia. In additon, the risk for neutropenia appears to be greatest in the earliest cycles of chemotherapy and withholding CSF in older patients until after an event has occurred may place them at an unacceptably high risk for serious infection and death. And, finally, data on elderly patients with various malignancies show that they benefit from chemotherapy as much as younger patients when it is administered at the standard recommended doses; early CSF use helps make this possible. Elderly patients who are treated with moderately aggressive chemotherapy should therefore be considered a special population in whom primary prophylaxis with CSF is warranted. Such an approach has been advocated by an advisory panel of the National Comprehensive Cancer Network (NCCN); the rationale is the greater risk of chemotherapy-induced neutropenia and its complications in elderly patients and the ability of G-CSF (granulocyte colony-stimulating factor) to reduce this risk (Table 3). Specifically, the NCCN guidelines for the management of elderly patients with cancer recommend the routine use of CSF in patients 70 years of age or older who are treated with CHOP or a regimen with similar dose intensity, and in patients 60 or older who are treated with induction or consolidation chemotherapy for acute myelogenous leukemia.[5] Conclusion The elderly are the single largest proportion of patients with cancer, and the majority of cancer-related deaths occur in this population. Elderly patients obtain comparable benefit from standard doses of chemotherapy as younger patients, but they are more susceptible to the myelotoxic effects of chemotherapy-in particular lifethreatening neutropenia-which often occur early. Investigation of clinical risk factors has consistently found that advanced age is a risk factor for neutropenic complications. When prophylactic CSF is administered early in the course of therapy and continued in all chemotherapy cycles it reduces the incidence and severity of neutropenia and associated complications, hence making it possible to use standard doses of chemotherapy. Such use should be routinely considered in elderly patients treated with moderately toxic chemotherapy regimens.


The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.


1. Balducci L: The geriatric cancer patient: Equal benefit from equal treatment. Cancer Control 8(2 suppl):1-25, 27-28, 2001.
2. Edwards BK, Howe HL, Ries LAG, et al: Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on US cancer burden. Cancer 94:2766-2792, 2002.
3. Jemal A, Thomas A, Murran T, et al: Cancer statistics, 2002. CA Cancer J Clin 52:23- 47, 2002.
4. Yancik R, Ries LA: Aging and cancer in America: Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 14:17- 23, 2000.
5. Balducci L, Yates J: General guidelines for the management of older patients with cancer. Oncology 14:221-227, 2000.
6. Lyman GH, Balducci L, Agboola Y: Use of colony-stimulating factors in the elderly cancer patient. Oncology Spectrums 2:414-421, 2001.
7. Balducci L, Hardy CL, Lyman GH: Hemopoietic reserve in the older cancer patient: Clinical and economic considerations. Cancer Control 7:539-547, 2000.
8. Crivellari D, Bonetti M, Castiglione- Gertsch M, et al: Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: The International Breast Cancer Study Group trial VII. J Clin Oncol 18:1412-1422, 2000.
9. Dees EC, O’Reilly S, Goodman SN, et al: A prospective pharmacologic evaluation of age-related toxicity of adjuvant chemotherapy in women with breast cancer. Cancer Invest 18:521-529, 2000.
10. Langer CJ, Manola J, Bernardo P, et al: Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: Implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94:173-181, 2002.
11. Lyman GH, Morrison VA, Dale DC, et al: Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma 44:2069-2076, 2003. See also
12. Caggiano V, Stolshek B, Delgado D, et al: First and all cycle febrile neutropenia hospitalizations (FNH) and costs in intermediate grade non-Hodgkin’s lymphoma (IGL) patients on standard-dose CHOP therapy (abstract 1810). Blood 98:431a, 2001.
13. Christman K, Muss HB, Case DL, et al: Chemotherapy of metastatic breast cancer in the elderly. The Piedmont Oncology Association experience. JAMA 268:57-62, 1992.
14. Kuderer NM, Cosler L, Crawford J, et al: Mortality and economic impact of hospitalization with febrile neutropenia in patients with breast cancer (abstract 106). Proc Am Soc Clin Oncol 22:27, 2003.
15. Zelenetz AD, Reider PA, Delgado DJ: Review of patterns of care among community physicians in intermediate grade NHL (IGL) reveals significantly greater planned and delivered dose attenuation in older patients (abstract 588). Blood 96:137a, 2000.
16. Agboola O, Crawford J, Dale DC, et al: Most patients treated with adjuvant chemotherapy for breast cancer receive substantially reduced dose intensity (abstract 110). Proc Am Soc Clin Oncol 22:28, 2003.
17. Yee KW, Pater JL, Pho L, et al: Enrollment of older patients in cancer treatment trials in Canada: Why is age a barrier? J Clin Oncol 21:1618-1623, 2003.
18. Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061-2067, 1999.
19. Kemeny M, Muss HB, Kornblith AB, et al: Barriers to participation of older women with breast cancer in clinical trials (abstract 2371). Proc Am Soc Clin Oncol 19:602a, 2000.
20. Dixon DO, Neilan B, Jones SE, et al: Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: The Southwest Oncology Group experience. J Clin Oncol 4:295-305, 1986.
21. Bastion Y, Blay JY, Divine M, et al: Elderly patients with aggressive non-Hodgkin’s lymphoma: Disease presentation, response to treatment, and survival—A Groupe d’Etude des Lymphomes de l’Adulte study on 453 patients older than 69 years. J Clin Oncol 15:2945- 2953, 1997.
22. Björkholm M, Ösby E, Hagberg H, et al: Randomized trial of r-metHu granulocyte colony-stimulating factor (G-CSF) as adjunct to CHOP or CNOP treatment of elderly patients with aggressive non-Hodgkin’s lymphoma (abstract 2655). Blood 94:599a, 1999.
23. Cress RD, O’Malley CD, Leiserowitz GS, et al: Patterns of chemotherapy use for women with ovarian cancer: A populationbased study. J Clin Oncol 21:1530-1535, 2003.
24. Mahoney T, Kuo YH, Topilow A, et al: Stage III colon cancers: Why adjuvant chemotherapy is not offered to elderly patients. Arch Surg 135:182-185, 2000.
25. Chen CI, Skingley P, Meyer RM: A comparison of elderly patients with aggressive histology lymphoma who were entered or not entered into a randomized phase II trial. Leuk Lymphoma 38:327-334, 2000.
26. Peake M. Elderly lung cancer patients in UK are undertreated. Presented at the 96th International Conference of the American Thoracic Society, May 5-10, 2000; Toronto, Ontario, Canada.
27. Goodwin JS, Samet JM, Hunt WC: Determinants of survival in older cancer patients. J Natl Cancer Inst 88:1031-1038, 1996.
28. Bonadonna G, Valagussa P, Moliterni A, et al: Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: The results of 20 years of follow-up. N Engl J Med 332:901-906, 1995.
29. Budman DR, Berry DA, Cirrincione CT, et al: Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J Natl Cancer Inst 90:1205-1211, 1998.
30. Epelbaum R, Faraggi D, Ben-Arie Y, et al: Survival of diffuse large cell lymphoma. A multivariate analysis including dose intensity variables. Cancer 66:1124-1129, 1990.
31. Kwak LW, Halpern J, Olshen RA, et al: Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: Results of a tree-structured survival analysis. J Clin Oncol 8:963-977, 1990.
32. Lepage E, Gisselbrecht C, Haioun C, et al: Prognostic significance of received relative dose intensity in non-Hodgkin’s lymphoma patients: Application to LNH-87 protocol. The GELA (Groupe d’Etude des Lymphomes de l’Adulte). Ann Oncol 4:651-656, 1993.
33. Rowe JM, Andersen JW, Mazza JJ, et al: A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: A study of the Eastern Cooperative Oncology Group (E1490). Blood 86:457-462, 1995.
34. Early Breast Cancer Trialists’ Collaborative Group: Polychemotherapy for early breast cancer: An overview of the randomised trials. Lancet 352:930-942, 1998.
35. Rosvold E, Langer CJ, McAleer C, et al: Advancing age does not exacerbate toxicity or compromise outcome in non-small cell lung cancer patients receiving paclitaxelcarboplatin (abstract 1846). Proc Am Soc Clin Oncol 18:478a, 1999.
36. Sargent D, Goldberg R, MacDonald J, et al: Adjuvant chemotherapy for colon cancer (CC) is beneficial without significantly increased toxicity in elderly patients (Pts): Results from a 3351 Pt meta-analysis (abstract 933). Proc Am Soc Clin Oncol 19:241a, 2000.
37. Chatta GS, Price TH, Stratton JR, et al: Aging and marrow neutrophil reserves. J Am Geriatr Soc 42:77-81, 1994
38. Shank WA Jr, Balducci L: Recombinant hemopoietic growth factors: Comparable hemopoietic response in younger and older subjects. J Am Geriatr Soc 40:151-154, 1992.
39. Bertini M, Freilone R, Vitolo U, et al: PVEBEC: A new 8-weekly schedule with or without rG-CSF for elderly patients with aggressive non-Hodgkin’s lymphoma (NHL). Ann Oncol 5:895-900, 1994.
40. Zagonel V, Babare R, Merola MC, et al: Cost-benefit of granulocyte colony-stimulating factor administration in older patients with non- Hodgkin’s lymphoma treated with combination chemotherapy. Ann Oncol 5(suppl 2):127-132, 1994.
41. Zinzani PL, Pavone E, Storti S, et al: Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin’s lymphoma. Blood 89:3974- 3979, 1997.
42. de Graaf H, Willemse PH, Bong SB, et al: Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer. Oncology (Basel) 53:289-294, 1996.
43. Balducci L, Repetto L: Increased risk of myelotoxicity in elderly patients with cancer: The case for routine prophylaxis with colonystimulating factor beginning in the first cycle of chemotherapy. Cancer. In press.
44. Heil G, Hoelzer D, Sanz MA, et al: A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood 90:4710-4718, 1997.
45. Balducci L, Extermann M: Management of cancer in the older person: A practical approach. Oncologist 5:224-237, 2000.
46. Webster J, Lyman GH: Use of G-CSF to sustain dose intensity in breast cancer patients receiving adjuvant chemotherapy: A pilot study. Cancer Control 3:519-523, 1996.
47. Zinzani PL, Storti S, Zaccaria A, et al: Elderly aggressive-histology non-Hodgkin’s lymphoma: First-line VNCOP-B regimen experience on 350 patients. Blood 94:33-38, 1999.
48. Gregory SA, Case DC Jr, Bosserman L, et al: 14 day CHOP in patients with aggressive non-Hodgkin’s lymphoma (NHL): Preliminary results (abstract 49). Proc Am Soc Clin Oncol 19:15a, 2000.
49. Moore TD, Patel T, Segal ML, et al: A single pegfilgrastim dose per cycle supports dose-dense (q14d) CHOP-R in patients with NHL (abstract 2245). Blood 100:571a, 2002.
50. Lyman GH: Risk assessment in oncology clinical practice: From risk factors to risk models. Oncology 17(suppl 11):8-13, 2003 (this supplement).
51. Wilson-Royalty M, Lawless G, Palmer C, et al: Predictors for chemotherapy-related severe or febrile neutropenia: A review of the clinical literature. J Oncol Pharm Pract 7:1-7, 2001.
52. Gomez H, Hidalgo M, Casanova L, et al: Risk factors for treatment-related death in elderly patients with aggressive non-Hodgkin’s lymphoma: Results of a multivariate analysis. J Clin Oncol 16:2065-2069, 1998.
53. Lyman GH, Delgado D: Risk and timing of hospitalization for febrile neutropenia among patients receiving CHOP-like regimens for intermediate-grade non-Hodgkin’s lymphoma (abstract 3085). Blood 100:780a, 2002.
54. Meza L, Baselga J, Holmes FA, et al: Incidence of febrile neutropenia (FN) is directly related to duration of severe neutropenia (DSN) after myelosuppressive chemotherapy (abstract 2840). Proc Am Soc Clin Oncol 21:255b, 2002.
55. Ozer H, Armitage JO, Bennett CL, et al: 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: Evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol 18:3558- 3585, 2000.
Loading comments...
Please Wait 20 seconds or click here to close