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Eur J Haematol 2006: 77: 378–386 doi:10.1111/j.1600-0609.2006.00739.

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Ó 2006 The Authors Journal compilation Ó 2006 Blackwell Munksgaard EUROPEAN JOURNAL OF HAEMATOLOGY

Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY
˚ rd G, Gasco ´ n P, Ludwig H. Evaluation of anaemia in patients Birgega with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY.
OnlineOpen: This article is available free online at

Gunnar Birgegård1, Pere Gascón2, Heinz Ludwig3

University Hospital, Uppsala, Sweden; 2Hospital Clinic, Barcelona, Spain; 3Wilhelminenspital, Vienna, Austria

Abstract: Objectives: Until recently, no prospective epidemiologic survey of lymphoma and multiple myeloma (L/MM) in European cancer patients had been conducted; furthermore, data on prevalence, incidence, and treatment patterns of L/MM were limited or unavailable. Here we define anemia prevalence, incidence, and treatment patterns, and identify anemia risk factors in European L/MM patients. Methods: Data for a subgroup of 2360 L/MM patients in the European Cancer Anaemia Survey (ECAS) were analyzed; variables included age, gender, tumor type/stage, cancer and anemia treatment, WHO performance status, and hemoglobin (Hb) levels. Results: 2316 patients were evaluable (1612 L and 704 MM). Anemia rate at enrollment was 52.5%. At enrollment, Hb levels correlated significantly with WHO scores (r ¼ )0.306, P < 0.001). Anemia prevalence during ECAS was 72.9% (MM, 85.3%; nonHodgkin’s lymphoma, 77.9%; Hodgkin’s disease, 57.4%); incidence in chemotherapy patients was 55.4%. Only 47.3% of patients anemic any time during ECAS received anemia treatment; overall Hb nadir for initiating treatment was 8.9 g/dL (epoetin, 9.5 g/dL; transfusion, 8.2 g/dL). Factors found to significantly (P < 0.03) increase anemia risk were low initial Hb, female gender, persistent/resistant disease, and platinum chemotherapy. Conclusions: L/MM patients have a high prevalence and incidence of anemia; however, anemia is not optimally treated. Anemia is common in L/MM patients and, given its known adverse impact on physical functioning and quality-of-life variables including fatigue and cognitive function, anemia management should be an integral part of their care. Predictive factors identified by ECAS may help clinicians develop optimal anemia treatment strategies for L/MM patients.

Key words: European cancer anaemia survey; anaemia; epoetin alpha; lymphoma; multiple myeloma Correspondence: Gunnar Birgegård, Department of Internal Medicine, University Hospital, 75185 Uppsala, Sweden Tel: +46 (018) 611 44 12 Fax: +46 (018) 611 00 00 e-mail: Accepted for publication 21 May 2006

Anemia is a serious and common complication in patients with non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease (HD), and multiple myeloma (MM) (1–5). Moullet et al. (2) reported the presence of anemia [hemoglobin (Hb) £ 12 g/dL for all patients over age 50; £ 11 g/dL for women under age 50] at diagnosis in 32% of 1077 patients with non-Hodgkin’s disease (range 17–39%, depending on histologic subtype), and Kyle et al. (6) reported anemia (Hb £ 12 g/dL) in 73% of 378

1027 patients with newly diagnosed MM. Several factors can cause anemia in patients with lymphoid malignancies or MM, including abnormal iron utilization, inappropriately low serum erythropoietin levels, a decrease of bone-marrow response to erythropoietin, hemolysis, and bonemarrow involvement (2, 7). However, anemia may also be caused or exacerbated by treatment with cytotoxic agents. Coiffier et al., in a retrospective chart survey of patients with various solid or non-

Ludwig et al. A total of 15 317 patients from 748 centers in 24 European countries were enrolled and were followed for up to 6 months. and/or iron] within 30 d of survey enrollment and at enrollment were recorded. which profiled cancer-related anemia in the European cancer population-at-large (9). disease status. Performance scores were based on the WHO scale. these patients had to be under the care of a physician or center specializing in cancer treatment. in accordance with the toxicity grading criteria from the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC). Patients enrolled were adults with a solid or hematologic malignancy. and current treatment patterns of cancer-related anemia. The survey evaluated the prevalence.7% and 34. data from patients with lymphoma or multiple myeloma (L/MM) who were included in the ECAS were analyzed.0 g/dL) was found to be 39. 9. reported the results of the European Cancer Anaemia Survey (ECAS).3% at enrollment and 67. NCI (14). and laboratory values (including Hb and hematocrit). Data collected at follow-up included performance status. or their treatment status. and current cycle number for patients receiving chemotherapy. It is now recognized that anemia may lead to symptoms that adversely affect physical status and diminish functional capacity and quality of life (QOL) in cancer patients (5.0–<10. and at survey completion. Because of the importance of anemia in patients with hematologic malignancies. respectively. elucidate the relationship between anemia and performance status as measured by WHO criteria. anemia therapy.9–8.Anemia in multiple myeloma and lymphoma myeloid hematologic malignancies treated at 24 centers in France. laboratory values.0 g/dL (moderate).9– 10. The objectives of these analyses were to define the prevalence and incidence of anemia in patients with L/MM.0 g/dL (severe). as well as its relationship to World Health Organization (WHO) performance status and risk factors for its development. based on the Common Toxicity Criteria. ECAS was a large. Moreover. tumor type and stage. in remission). incidence. and reason for survey completion (end of survey period.9%. and interaction between Hb level and treatment status.0% during the survey. Patient characteristics and baseline Hb level were examined with descriptive statistics. Briefly. Results of the analyses are described here. date of initial diagnosis. Materials and methods The methodology for ECAS has been described elsewhere (9). irrespective of their dis- ease status (newly diagnosed. performance status. death. final chemotherapy and radiotherapy regimens.5 g/dL) in patients with HD or NHL increased from 16. and private centers specializing in cancer care in 24 European countries. observational survey conducted in 748 academic. any combination of the preceding. Anemia was defined as an Hb level <12 g/dL. or none). early withdrawal) were recorded. decreased Hb level was found to correlate significantly (P < 0.24) and during the survey (range: Pearson r ¼ )0. In a recent publication. laboratory values.1% and 18. prospective. Additionally. which ranges from 0 (best possible score) to 4 (worst possible score). Anemia may also be associated with poorer prognosis and increased patient mortality (2. assess anemia treatment patterns. found that the prevalence of moderate anemia (Hb 8. 11–13). type of cancer treatment (surgery. to identify independent risk factors for anemia. The prevalence of anemia (Hb level <12. radiotherapy.27 to )0. and define risk factors for the development of anemia in this patient subgroup. anemia was further categorized as 11. All procedures met local Ethical Committee requirements and were conducted in accordance with the guidelines defined in the Declaration of Helsinki. Data collected at enrollment included age. A small difference between OR and 379 . at up to six evaluation points or monthly for up to 6 months at regular scheduled clinic visits. incidence of anemia was 53%. community. Statistical analyses were based on the pooled data from all the participating countries. dichotomous potential predictive factors determined a priori (from available demographic and clinical variables) were evaluated in bivariate analyses with the outcome measures to obtain unadjusted odds ratios (ORs) and then entered into a multivariate logistic regression equation to evaluate the predictive factors and develop adjusted odds ratios (AORs). 10). at the start of the fourth chemotherapy cycle (8). persistent/recurrent. lost to follow-up. also. performance status.30).0 g/dL (mild). Two-way anova models were used to determine WHO performance score at enrollment from Hb level at enrollment. Additionally. but not enrolled in a clinical trial. recombinant human erythropoietin (epoetin). gender. Data were collected at enrollment. chemotherapy.9% to 25. and the EORTC. hormone or immunotherapy. cancer treatment. cancer treatment and anemia therapy [transfusion. For statistical analyses.001) with poor performance scores at enrollment (Pearson r ¼ )0. epidemiologic. treatment status at enrollment. At survey completion. and <8.

0) 6 37 144 313 (1. treatment. Hodgkin’s disease.8) (62.8) (14. and underwent at least two chemotherapy cycles during the survey. Within this subpopulation were 1128 (47. 704 MM): excluded 44 ineligible patients with inconsistent diagnosis and treatment.0 (18–87) 141 393 314 254 (12.8) 143 167 100 96 229 18 250 2 (28. no treatment New diagnosis. TX.8) (19.1) 309 (28.4) 257 (53. L. This population was analyzed for demographics. n (%) None Radiotherapy (RT) Chemotherapy (CT) Concomitant RT/CT Hb level (g/dL) Mean (SD) Median (range) Hb category.2) (26.0 (5.5) (2.7) 209 (41.2 (16.3) (14. • Analysis Population (n ¼ 2179. or retrospective data.5) (30.9) 12.1) 91 (13. • Risk Factor Chemotherapy Population (n ¼ 678): included only patients who were neither anemic nor receiving anemia treatment at enrollment. of whom 1128 had NHL.6 (1.0% (1153/2135) were males and 46.4) (8.5) (37.1) 30 157 342 550 (2. 665 MM): further excluded 137 patients with no data beyond enrollment.0) (19.5) (17. Of the 2316 patients in this population at enrollment.8 (4. Results Patients A total of 15 367 patients were enrolled in ECAS. 1514 L.4%) with L/MM are the subject of this report.4) (26.0 (35-250) Fig.5) (23.7 (10.9) 67. received their first chemotherapy during ECAS. 380 .1–78.1) 21.2) (7.0 (18–89) 304 131 42 20 (61. and underwent at least one chemotherapy cycle. 20 MM): included only chemotherapy patients who were neither anemic nor receiving anemia treatment at enrollment.0) (49. treatment P/R Remission Treatment status.6) (50.4) (54. Patient demographics and baseline characteristics at enrollment Non-Hodgkin's lymphoma Age (yr) Mean (SD) Median (range) Age groups.1) 21. body mass index.5) 564 (55. The proportions of males and females were comparable Table 1.6) (25.3) 14 (2.5%) with MM.6) 31 171 269 210 (4.4) 332 (51.˚ rd et al. and 512 had HD.3) (22.9) 95 (8. 512 (21. 21.9) 276 (55.0 (12.0 (31–94) 10 185 224 285 (1.0–40. n (%) Male Female WHO score.0 (1.7 (15.3) 70.9 g/dL ‡12 g/dL Weight (kg) Mean (SD) Median (range) BMI Mean (SD) Median (range) Hodgkin's disease Multiple myeloma 57.4) 11. n (%) Grade 0 Grades 1–2 Grades 3–4 Disease status.4) (28.0) (45.2) 20.0 (2.2) 12.0–11.0% (982/2135) were females. NHL.8) 71.7) (17.5) (4.4) 129 (18. BMI.7) 245 247 412 195 474 15 595 4 (22.7) 20.9 (12. HD.6) (31. 193 L.3) (31.7) (43. MM.0 (5.1) 12.2) 93 102 381 121 318 14 341 16 (13. This population was analyzed for incidence of anemia in L/MM chemotherapy patients.1 (15. 54. lymphoma. Hb levels.5 (39–162) 70. This population was analyzed for frequency of anemia (prevalence).6) (54.9) (3.0–17.0) 69.0) 38. This population was analyzed for demographics.1) (0. • Anemia Chemotherapy Incidence Population (n ¼ 213. 1612 L. and anemia treatment during ECAS. Five patient populations were identified for statistical analysis (Fig.6) 312 (48.0–9.6–18. Demographics and clinical characteristics of patients in the Evaluable Population are summarized in Table 1.8) (35.0 g/dL 8.1) (39.7–42. n (%) New diagnosis. n (%) <8.0) 65.3 (3. 1): • Enrollment Population (n ¼ 2360): included 720 MM and 1640 L patients.7) 469 (68. non-Hodgkin’s lymphoma.5) 60.3) (33.2) (2.3) 225 (46.8%) patients with NHL. multiple myeloma.9) 11.3) 68. WHO scores.7) (51.7) (0.3 (4. who received their first chemotherapy during ECAS.6) (1.4) (46. Population flowchart for lymphoma/myeloma ECAS subgroup analysis.6–18.2) 35. of whom 2360 (15.7) (28. • Evaluable Population (n ¼ 2316. prevalence of anemia.7%) with HD. Birgega AOR was considered to indicate good independent predictive power of the predictor in question. and 720 (30.9 g/dL 10.9) 445 (44. n (%) <40 yr 40–59 yr 60–69 yr ‡70 yr Gender. standard deviation.0 (39–150) 71. and WHO scores at enrollment.0) 20.8) (40.1) SD.9 (14.6 (5.1 (12.8 (14.4) 685 (62.3) 12. 1.

9) 1021 1186 47 22 (44.0 g/dL 8. this high percentage was based on a small population (n ¼ 22).5 33. the mean age for patients with HD was substantially lower (38.7 yr). Hodgkin's disease.5–54. 52. At enrollment. compared with 12. Slightly more newly diagnosed patients with HD than with NHL or MM were receiving cancer treatment.9 28.0 62.8 45. HD. as were 37.9 g/dL.0) 47.2 31. respectively. however. At enrollment.9 % 14.9% vs.0–11. however. median age was 59.9 g/dL. and 9.9 n 342 144 269 % 31.1) (1.2% of HD patients were <40 yr of age. the majority of patients with MM had persistent/recurrent disease. 44.0–9.8 yr) or MM (65. Patients with MM were most frequently anemic (69. Anemia according to disease status and treatment status at enrollment (evaluable population) Anemic (%) Enrollment n (%) Disease status Newly diagnosed.6%).9 g/dL) were much more common in patients with MM (29. Treatment status was comparable across malignancies.8 39.001). compared with patients in the NHL and HD groups (Table 1). Hemoglobin category at enrollment Hemoglobin category (g/dL) <8.4%) or HD (8.0 0.4 30. Anemia levels categorized by disease status and treatment status at enrollment are shown in Table 3.0 g/dL).2 36.306.6% of patients with Hb levels 10.9 g/dL.5% (1187/2260) of patients with L or MM were anemic (Hb <12 g/dL).8 anemic at enrollment.4% of patients who were not anemic (Hb ‡12.306.4 3. WHO performance scores At enrollment. MM.1%).2%).0% of patients with NHL were anemic.5 37. and in a similar proportion of untreated patients (45.4 25.9% of patients with Hb levels 8.9 g/dL 10.9) 516 (22. Correlation between World Health Organization (WHO) performance score at enrollment and mean hemoglobin (Hb) levels (Spearman r ¼ )0.8–39.6 7.9 10.9 6.8 2.5 0 4. multiple myeloma.2 14. This compares with only 3.0 yr (range 18–94 yr). Conversely.2%) were observed in the MM group.6 42.5%) patients who were anemic had Hb levels of 10.7%) of patients receiving concomitant chemotherapy and radiotherapy were Table 3.0 % 51. whereas the majority of those with NHL or HD were newly diagnosed (Table 1).0–9. Nearly three-fourths (72.5 n 550 313 210 ‡12.4%).1) (2.7 20.6 n 157 37 171 8. compared with 23.4% of patients with Hb levels <8. 2. The lowest percentage of patients with WHO score 0 (18. as demonstrated by 40. When evaluated by malignancy. Fig.0 5.6–46. 49. As shown in Fig.4 58.9 26. 17. As shown in Table 2.1 10.7 28. low hemoglobin levels ( £ 9.4% with MM. 2.6 30. P < 0. P < 0.2 4.8 1.4% of those with HD. Anemia was also reported in 42. with treatment Persistent/recurrent disease In remission Treatment status No treatment Chemotherapy (CT) Radiotherapy (RT) Concomitant CT/RT Overall <8. with the majority of patients receiving chemotherapy (49. scores indicative of impaired performance (WHO scores of 3 or 4) were recorded for 34.7%) and the highest percentage of patients with WHO score 3 or 4 (13.001).4) 893 (38.8 37. 381 .5 14.8) 412 (17.9) (52.9 g/dL 481 (20.5% of MM patients being ‡70 yr of age.1 14. the proportion of males with NHL was slightly higher than that of females (55.6 72.8 37.1 yr) than that for patients with NHL (57.0 Diagnostic group NHL HD MM N 30 6 31 % 2. At enrollment.0 yr. In fact.8% of patients with NHL and 1. Significant correlations be- Table 2. most (28. 61. non-Hodgkin's lymphoma.7 2.7%) than in those with NHL (17. no treatment Newly diagnosed.1 63.7%) or no treatment (43.4 36.2 17.3 2.8 NHL. However. The mean age at enrollment for all L/MM patients (n ¼ 2303) was 56. MM occurred more often in older patients.0 50. being in this age range.0 g/dL.6% of patients receiving radiotherapy.6%) of patients receiving chemotherapy were anemic.0–11. more than half (58.Anemia in multiple myeloma and lymphoma for the groups with HD and MM. the prevalence of different Hb categories in patients with the individual diagnoses was not evenly distributed. there was a significant correlation between mean Hb level and WHO performance score at enrollment (Spearman r ¼ )0.0–9.0% and 4.0% of NHL and HD patients.0–11.2%). However.0–11.

7% for patients with persistent/recurrent disease. Fig.e. Nadir hemoglobin (category) for patients anemic at any time during the European Cancer Anemia Survey (ECAS). The incidence of anemia in chemotherapy patients was greater in the older age group. Fig. patients with MM were most likely to have Hb nadirs £ 9.4%) (Fig.6% for patients newly diagnosed and receiving treatment. Anemia treatment Only 47.9% in the group aged 60 yr and older (Fig. 382 . including time of enrollment. i.4% vs.4% became anemic. 51.259 to )0.8% for those in remission. 5). The frequency of anemia during ECAS categorized by disease status was 83.339.6% for those with HD). including the time of enrollment.9% experienced anemia at some time during ECAS (anemia prevalence).9 g/dL (59.0 g/dL (Fig. As shown in Fig.˚ rd et al. 71.9% in the group under 60 yr of age became anemic during ECAS compared with 65. 69. the frequency of anemia was increased for patients 60 yr of age and older compared with those under age 60. followed by patients with NHL (745/1030 or 77. Birgega tween mean Hb level and WHO performance score remained throughout the survey (range: Spearman r ¼ )0. 6.3%). Of 2165 patients in the L/MM Analysis Population. Among the three diagnostic groups..6% for patients newly diagnosed and not receiving treatment. 5. Fig. 3). Anemia according to age in patients anemic at any time during ECAS. P < 0. Frequency of anemia during ECAS by diagnosis. Frequency of anemia The frequency of anemia was determined in patients who were anemic at any time during ECAS.0%) of patients who were anemic at some time during ECAS had Hb nadirs less than 10.9%) and those with HD (271/472 or 57. Displaying a pattern similar to that seen at enrollment.5% for patients with NHL and 37. 6). Incidence of anemia Two hundred and thirteen chemotherapy patients fulfilled the criteria for inclusion in the Chemotherapy Incidence Population. 3. patients with MM were most frequently anemic (567/665 or 85. 48. More than half (52. 55. Anemia incidence according to age. 72. Values are provided for the total L/MM population and patients categorized by diagnosis. Of these patients.001). 4. and 54. 4.3% of L/MM patients who were anemic at any time during ECAS received treatment for Fig. The anemia that occurred during ECAS was substantial.

5 15 10 5 0 Newly diagnosed.95 1.99–5. being female increases anemia risk nearly three times. Of the 15 317 patients enrolled in ECAS.41 P-value <0.8 5.3%).5 times.3 g/dL have four Table 4.24–13.8 1. ECAS is the first published prospective survey with data on anemia in European cancer patients with L/MM.0002 1 AOR. anemia in L/MM patients can lead to fatigue. 2360 individuals were patients with L/MM. 23.99–4. Platinum was administered to 114 patients with L/MM (6. and epoetin plus transfusion and iron (2.3%). persistent/recurrent disease.0%). Four dichotomous variables were found to significantly (P < 0.0 95% CI 2.0001 0. Logistic regression odds ratios for anemia risk Predictor Initial Hb P/R disease Female sex Platinum treatment 1 OR 3. At enrollment.9 g/dL. hemoglobin. As would be expected.5 2. Additionally.8 Epoetin Transfusion ± Iron Iron only 22.03) increase the risk for becoming anemic: low initial Hb. 7. 10. persistent/recurrent disease.07 2. followed by those with NHL (77. P/R.4%) and transfusion plus iron (1.2 1.8%. epoetin plus transfusion (6. anemia. slightly more than half (52. incidence: 65.72–9.4 4. The frequency of anemia during ECAS.5 times the risk for anemia (Hb levels within-gender lowest 40th percentile). and treatment with platinum chemotherapy. as well as its incidence.7 g/dL for females.9%). epoetin plus iron (5. Hb. Table 4 shows the OR and AOR for each of these variables. confidence interval. 48.0% [comprised transfusion alone (19.3 19. reflecting the different pathophysiology of anemia in these three malignancies. or (iii) iron alone: 2.0 20 15.8% were in remission.5% were newly diagnosed and receiving cancer treatment. Prediction of anemia The Risk Factor Chemotherapy Population (n ¼ 678) was used to determine potential predictors for the development of anemia. Figure 7 shows the distribution of anemia treatment by disease status. which was determined in a specifically defined ÔincidenceÕ group (chemotherapy patients neither anemic nor receiving anemia treatment at enrollment.6)].31–2. and 4. 2316 of whom were evaluable. This may also partially explain why anemia was less frequent in patients with HD – these patients being younger than those in the other groups.5%) of the L/MM patients were anemic. 8. and suboptimal treatment of anemia in this population are concerns for several reasons. the demonstrated high rate of anemia in L/MM patients. 15 of 394 with HD (3.7 3. Patients treated for anemia received one of the following treatments: (i) epoetin therapy: 23. OR.1% vs.7%).29 1. odds ratio.2%) had MM. dyspnea.16 1. with more than 50% of anemic patients receiving no treatment.0001 <0.9 28. and 17 of 519 with MM (3. Discussion Fig.29 1. the highest frequency was observed among patients with MM (85. as with cancer patients in general. <12. CI. The overall Hb nadir for initiation of anemia treatment was 8.54 P-value <0. was greater in patients ‡60 yr of age than in patients <60 yr of age (frequency: 81.5 2.7 g/dL and males with an initial Hb <13. was found to be 55.9 1.0276 <0. The incidence of anemia in L/MM patients. (ii) transfusion: 21.54 1.2 g/dL. cardiovascular complications. The AORs (increase in odds of becoming anemic when the variables are considered simultaneously) indicate that females with an initial Hb <12. At enrollment <13.5 95% CI 2. first chemotherapy during ECAS. Taken together. Analyses of the data for the L/MM subgroup demonstrated the magnitude of both the prevalence and the incidence of anemia in this population.5 g/dL.0001 0.8 2.05–2. Anemia treatment was not initiated until Hb levels were relatively low.6% [comprised epoetin alone (9. adjusted odds ratio.9%) and HD (57. During ECAS.2%)].4%. Anemia treatment according to disease status.76–5.8%). particularly in elderly individuals.71–3. mean Hb level for initiation of epoetin was 9.3%). Persistent/recurrent disease increases anemia risk 1. and at least two chemotherapy cycles during the survey).9% of these patients had persistent/ recurrent disease.9%. treatment Persistent/ Recurrent In remission 2.0001 0. and treatment with platinum increases the risk for anemia 5. 65.3 g/dL for males.5 times. The survey was conducted to establish a comprehensive and clinically useful database to help clarify the complex factors surrounding the development of cancer-associated anemia (15).4 16. cognitive dysfunc383 .4%). these included 82 of 889 patients with NHL (9. and for transfusion was 8. no treatment Newly diagnosed.Anemia in multiple myeloma and lymphoma 30 Percentage of patients 25 21. it was found that treatment of cancer-associated anemia in L/MM patients is often suboptimal.2%. the frequency of anemia in the L/MM population rose to 72.3 20.0006 AOR 4.0001 <0.9% vs.2% were newly diagnosed and not receiving cancer treatment. female gender. First.2%).2 23.7%). the majority of whom (69.

9 4 38 55.4 19 47. 13. while the anemia incidence increases in older patients. with resultant improvement in QOL (16–18. Fatigue is especially problematic in the L/MM population. Although age and stage of disease have an impact on QOL. Additionally.016) on univariate analysis. Fatigue.3 g/dL for men. functional capacity.0 40 100. even though the Table 5. and other symptoms that adversely affect the patientsÕ physical status. the upper limit of which was within the normal reference range. anemia may contribute to poorer patient and therapeutic outcomes. data from patients who were neither anemic at enrollment nor receiving anemia treatment. logistic regression analyses have shown that the cumulative incidence of anemia in patients with NHL.7 g/dL for women).1 18 45. Iron as a single treatment for anemia was used infrequently (2. HD.˚ rd et al. and Waldenstro ¨ m’s macroglobulinemia. However.0 3 75.0 53 46. Therefore. HL.0 .7 15 37. emotional. Moreover.6 3 35 50. Despite high anemia rates and the known detrimental effects of anemia and its sequelae on patient QOL. Similar proportions of treated patients received transfusion (21. as many of these patients are older individuals who typically have a number of comorbidities that are already straining their physical and mental reserves and their functional capacity. Results of a comprehensive review of 60 published papers that reported survival of cancer patients according to either Hb levels or the presence of anemia showed that the estimated increase in risk of death was 65% overall.0 59 52. Associations have been found between low Hb levels and decreased survival in patients with NHL. less than half of the anemic L/MM patients in the survey received anemia treatment. cancer-associated anemia can often be corrected. as well as solid tumors (2. and economic consequences that impact not only the patients. or MM increases as the number of chemotherapy cycles they receive as treatment increases (Table 5). chronic lymphocytic leukemia.0 113 100. iron in combination with epoetin was also used infrequently (5.8%). and underwent at least one (validation population) or two (chemotherapy incidence population) chemotherapy cycles were analyzed with logistic regression to ascertain risk factors for the development of anemia. This is probably because. age was not a significant risk factor (P ¼ 0. One of the four risk factors identified was a low initial Hb level (<13. the significant (P < 0.0 3 75.0%). including reduced survival (2.6%). also known as the Linear Analog Scale Assessment or LASA)] (18).0 38 33. although platinum chemotherapy is not a usual treatment for these hematologic malignancies.0 3 75. <12.3 20 50. has been associated with significant physical. mantle cell lymphoma. the primary symptom of anemia.46) in the multivariate logistic regression model in the presence of other predictors.5 3 75. their overall QOL. which is thought to impart resistance to irradiation and some chemotherapeutic agents. Second. anemia may promote tumor hypoxia. Platinum therapy was also identified as a risk factor.5 2 50.8 6 43 62.3%) received chemotherapy that contained platinum. 28– 32).6 2 23 33. It was believed that identifying these factors would enable clinicians to judge more accurately which patients are most likely to become anemic so appropriate anemia management can be initiated in a timely manner (33). and to give rise to malignant progression (25–27). Birgega tion.0 63 55. whereas those treated with placebo had diminished QOL by most measures [which included the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Cancer Linear Analog Scale (CLAS. social. but often their families and/ or primary caretakers as well (19. and subsequently. analyses showed that 114 L/MM patients (6. with a 67% increased risk in anemic patients with lymphoma (4).4 Total 69 100. However. Post hoc analysis of prospectively collected data for a subset of patients with hematologic malignancies in a randomized placebo-controlled trial showed that patients treated with the erythropoietic stimulating agent epoetin alpha had improved QOL.0%) or epoetin (23. 11–13).4 7 17. The finding regarding platinum use in this subset of HM patients was consistent with the identification of platinum use as an anemia risk factor in the full ECAS population (34). however.5 3 75. 20).0 66 58.0 21 18.2 5 41 59.3 12 30. Cumulative incidence of anemia in patients with increasing numbers of chemotherapy cycles Cycle Lymphoma/myeloma groups Non-Hodgkin's lymphoma Hodgkin's lymphoma Multiple myeloma Total Count % Count % Count % Count % 1 12 17. not all patients developed anemia. Although anemia rates were high for patients with L or MM in the survey. the incidence of NHL and MM also increases in these patients. Studies have shown that patients living with L or MM and uncorrected anemia have a poor QOL (15–18).001) correlation shown between WHO performance scores and mean Hb at enrollment and during ECAS clearly demonstrated the potential reduction in QOL that can accompany anemia.0 4 100. received their first chemo384 therapy during ECAS. Age was identified as a significant risk factor (P ¼ 0. 21–25). 12. Of note.

Mayo Clin Proc 2003. prospective survey defining the prevalence. Cella D. Van Belle S.15(Suppl. inflammatory cytokines associated with anemia of chronic disease. quantitative review.339:1506–1514.113:172–179. and that anemia in L/MM patients is often untreated. Groopman JE. Beguin Y. Hasenclever D. Berg W. Many clinicians do not initiate anemia treatment until Hb levels are relatively low. Symptomatology of anemia. Felman P. Br J Haematol 2003. Bouafia F. Version 2. et al. Strasser K. Eur J Cancer 2004. which highlights the importance of treating anemia before there is a serious decline in QOL. Recombinant human erythropoietin in the anaemia of multiple myeloma and non-Hodgkin’s lymphoma. further limiting the rate of red blood cell production (35.91:1616–1634.Anemia in multiple myeloma and lymphoma importance of iron in maintaining adequate iron stores for erythropoiesis is well-known.25:43–46. Management of diseaserelated anemia in patients with multiple myeloma or chronic lymphocytic leukemia: epoetin treatment recommendations. Frequency and significance of anemia in nonHodgkin’s lymphoma patients. The mean Hb level for initiation of transfusion was 8. Indeed. NCI.28:7–14.40:2293–2306. Cancer 2001. In conclusion. 3. Bastit P. The EORTC guidelines (39). Kloczko J. Cazzola M. the overall Hb nadir for initiation of anemia treatment in L/MM patients in European community practices was 8. iron stores may be exhausted during the early part of treatment and a state of iron deficiency may be induced. Albain KS. The predictive factors and patterns of anemia treatment in L/MM identified by ECAS are important resources that may help clinicians develop optimal treatment strategies.9:1618–1626. Ludwig H. compared with HD patients.9 g/dL. Dumontet C. References 1. The European cancer anaemia survey (ECAS): a large.0 g/ dL) in more than half of patients affected. Castoldi G. Bethesda. Rodjer S. J Clin Oncol 1999. Factors influencing quality of life in cancer patients: anemia and fatigue. J Clin Oncol 1991. and for initiation of epoetin therapy was 9. ESA therapy should also be considered in asymptomatic patients in order to prevent further decline in Hb level. 5. 16. N Engl J Med 1998. Ferrara J. A prognostic score for advanced Hodgkin’s disease. Coiffier B. Coiffier B. LeBlanc M. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.37:1617–1623. 6. Guastalla JP. More often. MD [NLM 9810879]. this subgroup analysis of ECAS data shows that anemia is a widespread and serious problem among L/MM patients. Garcia-Sanz R. Ann Oncol 1998. Neidhart-Berard EM. As shown by this study.3:121–130. a frequent causative factor of cancer-related anemia. Semin Oncol 1998. Ward A. Ludwig H. 1):S29–S34. 4. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic. 17. producing functional iron deficiency. 12. 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