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Originally published as JCO Early Release 10.1200/JCO.2005.11.080 on June 13 2005 © 2005 American Society of Clinical Oncology. Hodgkin's Lymphoma in Elderly Patients: A Comprehensive Retrospective Analysis From the German Hodgkin's Study GroupFrom the Department I of Internal Medicine, University of Cologne; German Hodgkin Study Group, University of Cologne, Cologne; Department of Radiation Oncology, Ludwig Maximilian Universität München, Munich; and Department of Pathology, University Hospital of Würzburg, Germany Address reprint requests to Andreas Engert, MD, Department of Internal Medicine I, University Hospital of Cologne, Kerpener Str 62, 50924 Cologne, Germany; e-mail: a.engert{at}uni-koeln.de
PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients.
During the last three decades, major advances have been made in the therapy of Hodgkin's lymphoma (HL). This success is mainly based on the introduction of effective combination chemotherapy regimens and progress in radiation techniques. As a result, long-term failure-free survival (FFS) of 60% to 70% was obtained with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/ABVD-like regimens.1-4 More recently, 5-year FFS values of 82% to 89% were reported with dose- and time-intensified third-generation schedules such as bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), and others.5-7 However, these improvements have so far not been extended to elderly patients. Several analyses showed worse outcome of patients with advanced HL aged 50 to 65 years compared with younger patients when similar treatments were given.8-16 Advanced age at presentation is an independent negative risk factor. Two hypotheses were created to explain these findings. First, biologic differences such as more aggressive histology, different anatomic distribution of involved sites, and shorter history of disease adversely influence the prognosis of elderly patients.8,9,17-19 Second, aging itself and associated factors such as increased comorbidity,20 reduced tolerability of conventional therapy,11,21 more severe toxicity and treatment-related deaths,8,9,12,13,22 and poorer outcome after relapse16,23 generally contribute to the worse prognosis of elderly patients. In addition, the inclusion of unrelated deaths might obscure the analysis of elderly HL patients.24 Given that there is a lack of data from larger randomized trials, we performed a retrospective analysis of 4,251 HL patients enrolled onto the trials HD5 to HD9 of the German Hodgkin's Study Group (GHSG), to determine clinical presentation, treatment course, toxicity, and outcome of patients aged 60 years or older.
Patient Selection Between 1988 and 1998, 4,959 HL patients in early favorable, early unfavorable, and advanced stages were enrolled onto the second and third generation of GHSG clinical trials (HD4 to HD9). We excluded the HD4 study from the present analysis because only eight of 376 patients were 60 years or older. In general, patients had to be between 15 and 75 years, had to have biopsy-proven and newly diagnosed HL, and had to give written informed consent as to the participation in a clinical study. Patients in clinical stage I or II without risk factors were qualified for the HD7 trial for early favorable disease. Risk factors included large mediastinal mass, extranodal disease, elevated erythrocyte sedimentation rate (more than 50 mm/h in asymptomatic patients and more than 30 mm/h in patients with "B" symptoms), massive splenic involvement, and three or more involved nodal areas. Patients in clinical stage I or IIA with one or more risk factors, patients in clinical stage IIB without the first three risk factors, and patients in clinical stage IIIA without any risk factor were qualified for the HD5/HD8 trials for early unfavorable stages. The remainder of patients in clinical stage IIB and IIIA with risk factors were enrolled onto the HD5 (early unfavorable stages) or HD9/HD9elderly trials (advanced stages), respectively. We excluded the former group (332 patients) because we wanted to base our analysis on patients treated according to recent classifications only. Patients in clinical stage IIIB or IV were enrolled onto trials for advanced-stage disease (HD6/HD9/HD9elderly). Thus, this retrospective analysis consists of a total of 4,251 HL patients (Table 1). Of these, 372 (8.8%) were 60 years or older. Review of biopsy specimens by an expert panel of lymphoma pathologists was an obligatory part of the protocols. Review histology was available for 72% of all patients.
Pretreatment evaluation included medical history; physical examination; complete blood count; liver and renal function tests; erythrocyte sedimentation rate; chest radiography; abdominal ultrasound; computed tomography of chest, abdomen, and pelvis; bone marrow biopsy; and isotopic bone scan. In addition, a lung function test and echocardiography were routinely performed before treatment. Large mediastinal mass was defined as tumor measuring more than one third of the maximal thoracic diameter as determined on a posterior-anterior chest radiography. Bulky disease was defined as single lymph node involvement or tumor mass of more than 5 cm in any diameter. Stage of disease was defined according to the Ann Arbor classification.25 Patients were excluded from these studies if the disease was insufficiently staged, if pre-existing or concomitant diseases were present that precluded therapy according to protocol, or if patients (or their parents in patients younger than 18 years) refused therapy according to protocol. In the third generation, patients with composite lymphoma, previous chemotherapy or radiotherapy, or malignant disease in the last 5 years, or pregnant or lactating women were also excluded. Each patient gave written informed consent, which was based on the institutional review board guidelines.
Chemotherapy Regimens
Radiotherapy All sites of disease were defined and documented before chemotherapy. Radiotherapy was initiated 4 to 6 weeks after the end of chemotherapy. The total dose was between 30 and 40 Gy. The single-fraction dose was 1.8 to 2.0 Gy daily. EF-RT was administered to all patients with early-stage disease in the trials HD5 and HD7, and to patients in HD8 arm A. All patients in HD8 arm B received involved-field radiotherapy. Patients with advanced HL in HD6 and HD9 were given local radiotherapy only to regions of initial bulky disease (and slow responding areas in HD6) with 30 Gy or to regions of residual disease with 40 Gy.
Response Definition
Statistical Methods
Clinical Characteristics A total of 4,251 patients were eligible for this analysis; 372 patients (8.8%) were 60 years and older and 3,879 patients (91.2%) were younger than 60 years. The age distribution is shown in Figure 1. Table 3 lists the characteristics of these patients. The median age of the two cohorts was 65 and 31 years, respectively. There were more female patients in the elderly group (52% v 44%; P = .005). The following statistically significant differences were observed: more elderly patients had B symptoms (50% v 43%; P = .007), elevated erythrocyte sedimentation rate (59% v 51%; P = .002), mixed cellularity subtype (35% v 19%; P < .001), and poorer performance status (Karnofsky performance score < 80: 11% v 3%; P < .001). Less frequent were large mediastinal mass (9% v 20%; P < .001), bulky disease (49% v 60%; P < .001), and nodular sclerosis subtype (41% v 66%). Ann Arbor stage also differed significantly (P < .001); elderly patients were more frequently at the low and high ends. International Prognostic Score, which by definition includes age as one of the risk factors, was more unfavorable in elderly patients (IPS 4 to 7; 38% v 19%; P < .001). However, when age was removed from this calculation, this difference was no longer significant (age-adapted IPS 4 to 6; 13% v 11%; P = .72). Other characteristics did not differ significantly.
Administration of Therapy The course of treatment is summarized in Tables 4 and 5. There was an inverse correlation, particularly in elderly patients, between the intended number of chemotherapy cycles and the number of patients who received the full number of cycles. The difference between elderly and younger patients was statistically significant (P < .001). In addition, dose reduction occurred more often in the elderly. Seventy-five percent of elderly patients received the intended dose (more than 85% of planned dose) compared with 91% of younger patients (P < .001). Elderly patients with advanced disease were most prone to dose reductions (Table 5). Major treatment deviations classified as premature study termination were found in 26% of elderly patients compared with 11% in younger patients (P < .001). The most frequent reason for premature termination of therapy in elderly patients was extensive toxicity (9%), followed by patient's wish (6%) and progressive disease (4%). Premature termination of therapy occurred more often in patients with advanced HL in both age groups; the difference was more striking in elderly patients (Table 5).
Toxicity Acute toxicity (WHO grade 3 or 4) during chemotherapy is listed in Table 6. All adverse effects (except for nausea, urogenital, allergic reactions, skin reactions, and pain) were more frequent in elderly patients. The difference in risk of experiencing any chemotoxicity of grade 3 or 4 was statistically significant (83% v 75%; P = .005). The most frequent toxicities in elderly patients apart from alopecia were hematologic. Leukopenia WHO grade 3 or 4 occurred in 74% of elderly and in 61% of younger patients, anemia occurred in 17% of elderly and 11% of younger patients, and thrombocytopenia occurred in 17% of elderly and 11% of younger patients. In general, severe toxicities (WHO grade 4) occurred more often in elderly patients (42% v 27%; P < .001); notably, the most frequent severe toxicity was leukopenia, with 38% of elderly versus 23% of younger patients (P < .001). Infection grade 3 or 4 during chemotherapy and fatal acute treatment-related events during chemotherapy or radiotherapy were also more often observed in the elderly (15% v 6% and 6% v 0.6%, respectively; P < .001 for both).
Disease Control and Survival The overall response rate was similar in the two age groups, with a slightly lower rate of complete remissions (86% v 90%) and higher rate of relapse (14% v 10%) in elderly patients (Table 7). Five percent of patients had progressive disease, and there was no difference between the two groups. In sharp contrast, the 5-year FFTF was significantly lower in elderly patients compared with younger patients (60% v 80%; difference, 19%; 95% CI, 14% to 25%; P < .001; Fig 2A). Excluding the events unrelated to HL, the difference remained significant (difference, 9%; 95% CI, 4% to 14%; Fig 2B). The 5-year OS was also significantly lower for elderly patients (65% v 90%; difference 25%; 95% CI, 20% to 31%; P < .001; Fig 2C). Cox regression analysis stratified by chemotherapy confirmed these results, and revealed a significantly increased risk of treatment failure in elderly patients (hazard ratio, 2.0; 95% CI, 1.7 to 2.4; P < .001) or death (hazard ratio, 3.9; 95% CI, 3.2 to 4.8; P < .001). A total of 141 of 372 (38%) elderly patients and 420 of 3,879 (11%) younger patients died during the observation period. The most frequent cause of death in both groups was HL (Table 8). However, more deaths as a result of toxicity occurred in elderly patients (6% acute toxicity, 7% cardiorespiratory, 6% secondary malignancy, 5% other). In contrast, treatment-related death in younger patients occurred in less than 2% of patients. Secondary malignancies occurred more often in elderly patients (Table 8). There were a total of 39 (10%) secondary neoplasias in elderly patients compared with 140 secondary neoplasias (4%) in younger patients.
The objective of this analysis was to determine clinical risk factors, toxicity of treatment, and outcome for elderly HL patients. The results from this analysis involving a total of 4,251 patients (of whom 8.8% were  60 years of age) are as follows. First, older patients differ from younger HL patients in their risk factor profile. Second, during treatment, older patients experience more severe leucopenia (grade 4, 38% v 23%) and, consequently, more severe infections. This results in a lower relative dose of treatment given in elderly patients. Third, the treatment outcome for elderly patients is poorer in terms of OS (65% v 90% at 5 years) and FFTF (60% v 80% at 5 years). The outcome results are not attributable to differences in treatment or study allocation between younger and elderly patients because statistical tests were stratified by chemotherapy regimen. However, differences in the risk factor profile may be due to the retrospective nature of the analysis. Within population-based studies, the proportion of HL patients older than 60 years ranges between 20% and 44%.12,30,31 The proportion of elderly patients participating in prospective trials is considerably lower. The study entry criteria for most clinical trials are such that older patients with severe comorbidity and poor performance status cannot be enrolled. Generally, more elderly HL patients were represented in studies performed in the 1970s or 1980s. As an example, earlier Cancer and Leukemia Group B studies included 19% of patients older than 60 years.9 However, central pathology review in these historical studies was not performed. A more recent retrospective re-evaluation of elderly HL patients diagnosed decades ago indicates that a substantial proportion of elderly patients with B-cell lymphomas were initially misdiagnosed as having HL. Thus, meaningful studies in elderly patients require a reference pathology expert diagnosis.32 Accordingly, elderly patients represented 8% of all diagnoses in the Cancer and Leukemia Group B follow-up trial, which included pathology review.19 In our analysis, we found several statistically significant differences in disease-related characteristics between younger and older HL patients. Elderly patients presented more frequently with B symptoms, elevated sedimentation rate, mixed cellularity (MC) histologic subtype, and poorer Karnofsky performance score. Less frequent were bulky disease, large mediastinal mass, and nodular sclerosis (NS) subtype. Although MC subtype occurred more often in elderly patients (35% v 19%), NS histology was still most frequently observed in both age groups (41% and 66%). Others have reported similar findings,11,14,19 although there are conflicting data.9,12,24 More recent studies or those with pathology review13,19,24 observed fewer patients with lymphocyte predominant and lymphocyte depleted.9-11,33 This reflects improvement in histomorphology allowing a more precise classification of different HL subtypes and distinction of HL from NHL. In accordance with our findings, elderly patients generally present more often with poorer risk factors.8,18,21,33 It is unlikely that the differences in disease-related characteristics alone could explain the survival differences observed between the two age groups. When the IPS in the present analysis was calculated excluding age, the two age groups were no longer different in terms of age-adapted risk. Thus, tumor biology, older age itself, and other factors related to comorbidity probably contribute to the worse outcome of elderly patients. Elderly patients were less likely to complete the full intended course of therapy. The most frequent reason for premature termination of both chemotherapy and radiotherapy was excessive toxicity. Considering only the intended number of treatment cycles, fewer elderly patients received the full number of cycles. Dose adjustment was necessary significantly more often in older patients. This difference was most evident in patients with advanced disease. The administration of more intensive treatment such as BEACOPP6 resulted in more dose reductions and early withdraws in elderly patients (Table 5). Thus, the dose-intensity delivered was lower, explaining the poorer outcome of elderly patients, particularly those in advanced stages. In line with these findings, the randomized HD9elderly trial showed no benefit of BEACOPP baseline compared with COPP/ABVD in patients older than 65 years.34 In addition, the subgroup analysis of the HD9 study revealed no improvement of outcome in patients who were 60 to 65 years of age treated with both BEACOPP variants compared with those treated with COPP/ABVD.6 In the present analysis all relevant adverse effects occurred more often in elderly patients. Above all, leukopenia, infections, and cardiorespiratory toxicity were most likely the limiting factors in treatment delivery and contributed substantially to the higher treatment-related mortality in the elderly. Increased toxicity and reduced tolerance of treatment in elderly patients associated with worse outcome has also been observed by other authors.9,11,12,21,22,24 Adequately staged elderly patients receiving appropriate doses of therapy can achieve responses comparable to those in younger patients.8,11,13,14,21,23 This was also seen in the present analysis, in which the CR rate was not significantly different (86% v 90%). There was also no difference in terms of progressive disease observed (6% in both age groups). In contrast, 5-year OS and FFTF were significantly inferior in elderly patients. An increased number of treatment-related deaths contributed to the worse outcome of elderly patients. The treatment outcome for elderly patients is in line with earlier reports from other groups.10,14,21 In most of these studies however, selected elderly patients enrolled onto standard institutional treatment protocols were analyzed. Retrospective population-based studies reported poorer response and survival in elderly patients.8,9,11-13,16,19,33 In these series, a large proportion of patients received no treatment, radiotherapy only, or a variety of chemotherapy regimens without anthracycline or with reduced anthracycline dose. Elderly patients treated with anthracycline-containing regimens are known to have a significantly better treatment outcome.14,31 To improve health care for a steadily growing proportion of elderly patients, clinical studies specifically addressing these patients will become increasingly important. In the light of more pronounced risk factors, more frequent comorbidity, and higher risk of severe toxicity in elderly patients, new strategies are warranted. Attention should also be paid to a comprehensive assessment before treatment. In addition, closer monitoring of toxicity, improvement of supportive care, and the development of new regimens with sufficient efficacy and better tolerability are needed. Our group is thus currently evaluating two new regimens in patients aged 60 to 75 years that are derived from the BEACOPP regimen or from ABVD. In these regimens, putatively more toxic drugs are deleted or those with a lower toxic profile are substituted. In conclusion, this large retrospective analysis of elderly HL patients indicates that higher mortality during treatment, as well as lower dose-intensity, are the major factors explaining the poorer overall outcome.
The authors indicated no potential conflicts of interest.
Supported by The German Hodgkin's Study Group, which is supported by the Deutsche Krebshilfe and is part of the Kompetenznetz Maligne Lymphome, which is supported by the Bohdesministerium für Bilding und Forschung. Authors' disclosures of potential conflicts of interest are found at the end of this article.
1. Canellos GP, Anderson JR, Propert KJ, et al: Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327:1478-1484, 1992[Abstract]
2. Viviani S, Bonadonna G, Santoro A, et al: Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: Ten year results. J Clin Oncol 14:1421-1430, 1996 3. Connors JM, Klimo P, Adams G, et al: Treatment of advanced Hodgkin's disease with chemotherapy-comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: A report from the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 15:1638-1645, 1997[Abstract]
4. Duggan DB, Petroni FR, Johnson JL, et al: Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: Report of an Intergroup trial. J Clin Oncol 21:607-614, 2003
5. Horning SJ, Hoppe RT, Breslin S, et al: Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: Mature results of prospective clinical trial. J Clin Oncol 20:630-637, 2002
6. Diehl V, Franklin J, Pfreundschuh M, et al: Standard and increased-dose BEACOPP chemotherapy compared with COPP/ABVD for advanced Hodgkin's disease. N Engl J Med 348:2386-2395, 2003
7. Radford JA, Rohatiner AZ, Ryder WD, et al: ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease. J Clin Oncol 20:2988-2994, 2002 8. Austin-Seymour MM, Hoppe RT, Cox RS, et al: Hodgkin's disease in patients over sixty years old. Ann Intern Med 100:13-18, 1984 9. Peterson BA, Pajak TF, Cooper MR, et al: Effect of age on therapeutic response and survival in advanced Hodgkin's disease. Cancer Treat Rep 66:889-898, 1982[Medline] 10. Bosi A, Ponticelli P, Casini C, et al: Clinical Data and therapeutic approach in elderly patients with Hodgkin's disease. Haematologica 74:463-473, 1989 11. Erdkamp FL, Breed WP, Bosch LJ, et al: Hodgkin's disease in the elderly. Cancer 70:830-834, 1992[CrossRef][Medline]
12. Enblad G, Glimelius B, Sundstrom C: Treatment outcome in Hodgkin's disease in patients above the age of 60: A population-based study. Ann Oncol 2:297-302, 1991
13. Levis A, Depaoli L, Urgesi A, et al: Probability of cure in elderly Hodgkin's disease patients. Haematologica 79:46-54, 1994
14. Weekes CD, Vose JM, Lynch JC, et al: Hodgkin's disease in the elderly: Improved treatment outcome with a doxorubicin-containing regimen. J Clin Oncol 20:1087-1093, 2002 15. Macpherson N, Klasa RJ, Gascoyne R, et al: L: Treatment of elderly Hodgkin's lymphoma patients with a novel 5-drug regimen (ODBEP): A phase II study. Leuk Lymphoma 43:1395-1402, 2002[Medline]
16. Kim HK, Silver B, Li S, et al: Hodgkin's disease in elderly patients ( 17. Lokich JJ, Pinkus GS, Moloney WC: Hodgkin's disease in the elderly. Oncology 29:484-500, 1974[Medline] 18. Wedelin C, Björkholm M, Biberfeld P, et al: Prognostic factors in Hodgkin's disease with special reference to age. Cancer 53:1202-1208, 1984[CrossRef][Medline] 19. Mir R, Anderson J, Strauchen J, et al: Hodgkin's disease in patients 60 years of age or older: Histologic and clinical features of advanced-stage disease—The Cancer and Leukemia Group B. Cancer 71:1857-1866, 1993[CrossRef][Medline] 20. van Spronsen DJ, Janssen-Heijnen MLG, Breed WPM, et al: Prevalence of co-morbidity and its relationship to treatment among unselected patients with Hodgkin's disease and non-Hodgkin's lymphoma, 1993-1996. Ann Hematol 78:315-319, 1999[CrossRef][Medline] 21. Diaz-Pavon JR, Cabanillas F, Majlis A, et al: Outcome of Hodgkin's disease elderly patients. Hematol Oncol 13:19-24, 1995[Medline]
22. Levis A, Depaoli L, Bertini M, et al: Results of a low aggressivity chemotherapy regimen (CVP/CEB) in elderly Hodgkin's disease patients. Haematologica 81:450-456, 1996 23. Specht L, Nissen NI: Hodgkin's disease and age. Eur J Haematol 43:127-135, 1989[Medline] 24. Guinee VF, Geoffrey GC, Durand M, et al: The prognosis of Hodgkin's disease in older adults. J Clin Oncol 9:947-953, 1991[Abstract] 25. Lister TA, Crowther D, Sutcliffe S, et al: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Costwolds meeting. J Clin Oncol 7:1630-1636, 1989 [Erratum: J Clin Oncol 8:1602, 1990]
26. Engert A, Schiller P, Josting A, et al: Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: Results of the HD8 trial of the German Hodgkin's Study Group. J Clin Oncol 21:3601-3608, 2003
27. Loeffler M, Diehl V, Pfreundschuh M, et al: Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease. J Clin Oncol 15:2275-2287, 1997
28. Sieber M, Tesch H, Pfistner B, et al: Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: Final results of the German Hodgkin's Lymphoma Study Group Trial HD5. J Clin Oncol 20:476-484, 2002
29. Diehl V, Sieber M, Rueffer U, et al: BEACOPP: An intensified chemotherapy regimen in advanced Hodgkin's disease. Ann Oncol 8:143-148, 1997 30. Proctor SJ, Rueffer JU, Angus B, et al: Hodgkin's disease in elderly: Current status and future directions. Ann Oncol 13:133-137, 2002 (suppl 1)
31. Landgren O, Algernon C, Axdorph U, et al: Hodgkin's lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis. Haematologica 88:438-444, 2003 32. Miller TP, LeBlanc M, Braziel RM, et al: Was the bimodal age incidence of Hodgkin's lymphoma a result of mistaken diagnoses of Non-Hodgkin's lymphoma? Blood 100:3048A, 2002 33. Walker A, Schoenfeld E, Lowman JT, et al: Survival of the older patients compared with the younger patient with Hodgkin's disease. Cancer 65:1635-1640, 1990[CrossRef][Medline]
34. Ballova V, Rueffer JU, Haverkamp H, et al: A prospectively randomized trial performed by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (HD9elderly). Ann Oncol 16:124-131, 2005 Submitted January 6, 2005; accepted April 14, 2005.
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
