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  • 1
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1313-1313
    Abstract: Purpose: Several scores have described gender as an important prognostic factor in patients with Hodgkin’s lymphoma (HL), particularly in advanced-stages. However, so far there is no larger analysis to systematically evaluate possible gender-specific factors. The purpose of this analysis was to investigate sex differences with regard to pre-treatment and therapy-related variables and to evaluate their influence on the outcome of HL patients. Patients and Methods: From 1988 to 1998 the GSHG conducted two generations of clinical trials for early, intermediate and advanced HL (HD4 - HD9). The present analysis comprises 4626 patients of all stages, aged 15 to 75 years, who were enrolled into these multicenter studies and treated according to the GHSG-study protocols. Results: At a median observation time of 5.5 years, 2050 female and 2576 male patients were suitable for this retrospective analysis. Patients in each group had very similar profiles in terms of age, performance status, stage, histological subtype, clinical risk factors and prognostic factors. Slightly more nodular sclerosis subtypes and mediastinal masses were observed in women. In contrast, more men had a mixed cellularity subtype, older age, advanced stage of disease, and B-symptoms at diagnosis. Acute chemotherapy-related toxicity was distributed almost equally. However, there was more hematotoxicity in females. This difference was most obvious for leucopenia [WHO grade III/IV: 69.9 % versus 55.2 %]. Importantly, there was no higher risk of infections in female patients. Response rates being similar in both groups, however, a lower rate of relapse and death was observed in females. Univariate analyses revealed significant better outcome in terms of FFTF and OS for females. In multivariate analyses, sex was not identified as an independent prognostic factor, however, lower stages of disease (p & lt;.0001), less B-symptoms (p & lt;.0001), younger age (p & lt;.0001), and leucopenia grade III/IV (p & lt;.0001) were significant variables to which better outcome in females can be related. Particularly, the high prevalence of leucopenia grade III/IV during chemotherapy has a clear impact on better FFTF in females. The smaller proportion of males expressing severe leucopenia also had better outcomes. In addition, when only those patients were included who developed leucopenia grade III/IV within the first two cycles of chemotherapy, the factor maintains its protective role. Conclusion: In this large retrospective analysis of the GHSG database, a better outcome is observed for female patients compared to male patients with HL. The protective role of severe leucopenia supports the rationale for a more individualized therapy, that may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2005
    In:  Journal of Clinical Oncology Vol. 23, No. 31 ( 2005-11-01), p. 8003-8011
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 31 ( 2005-11-01), p. 8003-8011
    Abstract: Several scores have described sex as a prognostic factor in patients with Hodgkin's lymphoma (HL). However, little is known how sex-specific factors influence treatment outcome. We systematically investigated sex differences with regard to pretreatment characteristics and therapy-related variables, and examined their influence on the outcome of HL patients. Patients and Methods This analysis comprises 4,626 HL patients of all prognostic risk groups who were enrolled onto the multicenter studies HD4 to HD9 of the German Hodgkin Study Group. At 5.5 years, 2,050 female and 2,576 male patients were analyzed. Results Male and female patients had similar prognostic factors. There was more acute chemotherapy-related hematotoxicity in women, especially more severe leucopenia (WHO grade 3/4, 69.9% female and 55.2% male; P 〈 .0001). Importantly, this did not translate into more infections. Female patients had similar response rates but fewer relapses and deaths, leading to a significantly better freedom from treatment failure (FFTF; at 66 months, 81% female [95% CI, 79% to 82%] and 74% male [95% CI, 72% to 76%] ). Severe leucopenia during chemotherapy was strongly associated with better FFTF, both for males and females. In addition, when only those patients who developed severe leucopenia within the first two cycles of chemotherapy were included, the factor maintained its protective role. Conclusion The protective role of severe leucopenia suggests the testing of a more individualized therapy. In future trials, this therapy may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2005
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2005
    In:  European Journal of Haematology Vol. 75, No. s66 ( 2005-07), p. 125-134
    In: European Journal of Haematology, Wiley, Vol. 75, No. s66 ( 2005-07), p. 125-134
    Abstract: Abstract:  Hodgkin's Lymphoma (HL) has developed to one of the best curable human cancers and overall about 80% of patients experience long‐term disease free survival. Therefore, current treatment strategies aim at further improving treatment outcome, thereby trying to by minimize therapy‐induced complications, such as infertility, cardiopulmonary toxicity, and secondary malignancies. Ongoing trials investigate a reduction of chemotherapy in terms of dose or cycles given, and the application of lower radiation doses and smaller radiation fields. For patients with a specific high‐risk profile, new approaches with more intense drug combinations are currently being investigated. Moreover, the advent of effective salvage high‐dose therapy for relapsed disease and a better understanding of prognostic factors have further improved the management of HL. Here, we summarize current strategies of the German Hodgkin Study Group (GHSG) in diagnostics and treatment of primary and relapsed HL, together with recent approaches for specific subgroups of HL patients.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2005
    detail.hit.zdb_id: 2027114-1
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2674-2674
    Abstract: Purpose: A systematic analysis of gender-specific factors in Hodgkin’s lymphoma (HL) studies previously revealed a better outcome for female HL patients. Factors contributing to better prognosis among female patients not only included more favorable risk factors at diagnosis, but also more treatment-induced severe leuopenia (WHO grade III/IV). The purpose of the current analysis was to characterize and investigate the protective role of severe leucopenia for both, male and female HL patients. Patients and Methods: 4626 HL patients including 2050 females (f) and 2576 males (m) of all prognostic risk groups who were enrolled into the multicenter studies HD4-HD9 of the GHSG were evaluated. The median follow-up after treatment was 5.5 years. Results: Female patients had a significantly better freedom from treatment failure (FFTF) with 81% at 66 months (95% confidence interval 79% – 82%), when compared with male patients (74%; 72% – 76%; p & lt;.0001). This was in part related to the occurrence of more acute chemotherapy-related leucopenia (WHO grade III/IV): 69.9% in female patients and 55.2% in male patients (p & lt;.0001). Furthermore, severe leucopenia during chemotherapy was strongly associated with better FFTF for both, male and female patients. Separate multivariate analyses showed that severe leucopenia remained significant when only male patients were included (0.011). In addition, patients who developed severe leucopenia within the first two cycles of chemotherapy also had a significantly better FFTF (p=.0002) compared with all other patients (Klimm et al, JCO in press). When considering patients with advanced HL undergoing BEACOPP in baseline or escalated dose, the presence of severe leucopenia during chemotherapy (p=.0074) was associated with a better outcome. This finding was also confirmed when only the first two cycles of treatment were analyzed (p =.0205). Conclusion: The protective role of severe leucopenia suggests evaluating of a more individualized therapy in future trials, that may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2668-2668
    Abstract: Introduction: Due to substantial clinical progress over the past decades, the outcome of patients with Hodgkin’s Lymphoma (HL) has improved with a long-term disease free survival of nearly 80%. Even patients with advanced-stage HL show a five year freedom from treatment failure (FFTF) of 87% and overall survival (OS) of 91% when treated with 8 cycles of BEACOPPescalated (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbacine, prednisone). However, BEACOPPescalated has been associated with some acute and long-term treatment related mortality (TRM). We thus analysed the incidence, clinical features and risk factors for TRM of patients treated with BEACOPPescalated in the HD12 multicenter trial of the GHSG performed between 1998 and 2002. The HD12 was conducted for advanced HL patients (Stage IIB with large mediastinal mass and/or extranodal involvement, stage III/IV). All patients received 8 cycles of chemotherapy either 8x BEACOPPescalated (Arm A/B) or 4xBEACOPPescalated + 4xBEACOPPbaseline (Arm C/D) +/− 30Gy radiation on bulk and residual tumor. Results: In this study, 43 patients (3.1%) from a total of 1392 included died from TRM. 5 patients were excluded from this analysis because of various reasons (change of fist-line therapy due to toxicity, TRM in BEACOPPbaseline) 38 patients were eligible for this analysis. 30 patients (79%) had infectious complications, 6 (16%) cardiac events such as arrhythmia or heart failure, 1 patient died due to bleomycin-related toxicity and 1 case remained unclear. 25 patients (66%) were older than 50 years in contrast to the whole HD12 study population with only 17% of patients being older than 50. There was no statistical difference between those cases with treatment related mortality and the whole study population in terms of other clinical risk factors such as gender, B-symptoms, extranodal involvement, stage of disease, large mediastinal mass or elevated ESR. There was also no difference between the 4 study arms. Most events occurred during the first 4 courses of BEACOPPescalated (79%) with the majority during the first cycle (n = 12; 32%). 23/26 (89%) of patients who died during cycles 2 – 8 had prior WHO grade III/IV leucopenia or infection. Conclusion: Patient age and toxicity in previous cycles are the most obvious risk factors for TRM in patients with advanced HL undergoing BEACOPPescalated chemotherapy. In the HD12 study, the use of G-CSF was mandatory and most patients received their treatment on an outpatient basis. Thus, possible measures to reduce toxicity with this treatment include the prophylactic use of antibiotics as well as treating those with risk factors at least for the first course as inpatients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 20, No. 2 ( 2002-01-15), p. 476-484
    Abstract: PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin’s lymphoma can be improved by rapid application of non–cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin’s lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin’s lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P = .010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each). CONCLUSION: Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin’s lymphoma and produce excellent long-term treatment results.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2002
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 5 ( 2007-02-10), p. 579-586
    Abstract: Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Methods The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [ 18 F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations. Results New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. Standardized definitions of end points are provided. Conclusion We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
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  • 8
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1309-1309
    Abstract: Introduction: LPHD differs in histological and clinical presentation from cHD. Treatment of LPHD patients (pts) using standard Hodgkin disease (HD) protocols leads to complete remission (CR) in more than 95% of pts. However, differences in terms of relapse rates, survival and freedom from treatment failure (FFTF) between clinical stages of LPHD and cHD pts were suggested by a recent intergroup analysis. To obtain a more comprehensive picture, we reviewed all LPHD-cases registered in the GHSG database and compared patient characteristics and treatment outcome with cHD pts. Patients and methods: We retrospectively analysed 8298 HD pts treated within the GHSG trials (HD4 to HD12): 394 LPHD pts and 7904 cHD pts. From 394 LPHD pts 63% were in early stage, 16% in intermediate and 21% in advanced stage of disease. Of the 7904 cHD pts analysed, 22% were in early, 39% in intermediate and 39% in advanced stages. 9% of LPHD pts had B symptoms compared to 40% in cHD pts. Results: 87.5% LPHD pts reached CR/CRu compared to 81.1% cHD pts. 0.3% LPHD pts developed progressive disease (PD) compared to 3.7% cHD. The relapse rate of LPHD pts was very similar to cHD (6.9%). 0.8% LPHD pts and 3.1% cHD had early relapse, 6.9% LPHD pts and 4.2% cHD pts suffered from late relapse. LPHD pts with late relapse were in intermediate stages (12.5%). In contrast, only 3.9% of cHD pts in intermediate stages had late relapses. There were 2.5% secondary malignancies in LPHD and 3.7% in cHD pts. 4.3% LPHD pts and 8.8% cHD pts died. The FFTF rates for LPHD or cHD pts at a median observation of 41 or 48 months, respectively were as follows: early stages 93% vs. 87%, in intermediate stages 87% vs. 85% and in advanced stages 77% vs. 75%. The OS rates for LPHD or cHD pts were 98% vs. 96% for early stages, 94% vs. 93% for intermediate stages and 91% vs. 87% for advanced stages. The multivariate analysis of prognostic and risk factors will be presented. Conclusion: cHD pts present more frequently with advanced stages and B symptoms compared to LPHD pts. Comparing LPHD and cHD pts we found differences in treatment outcome in respect of CR/CRu, progressive disease and mortality. Surprisingly, there were no differences in terms of relapses. The majority of late relapses in LPHD pts were in intermediate stages. In contrast to previous reports, our data suggest that relapses in LPHD and cHD pts seem to be comparable and not more frequent. Thus new treatment strategy for LPHD pts in intermediate stages should be considered.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 1306-1306
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1306-1306
    Abstract: Background: With improved prognosis of patients with Hodgkin’s lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis of the German Hodgkin Lymphoma Study Group (GHSG) database to determine clinical presentation, toxicity of treatment and outcome of elderly HL patients. Methods: A total of 4251 patients included in the GHSG studies HD5-9 were analysed of whom 372 (8.8%) were 60 years or older and 3879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, failure free survival (FFTF) and overall survival (OS) were compared. Results: The median age of the two cohorts was 65 and 31 years, respectively. Statistically significant differences in patient characteristics were as follows: elderly patients had more frequently mixed cellularity subtype (35% vs. 19%), B-symptoms (50% vs. 43%) and elevated ESR (59% vs. 51%). Less frequently observed in elderly patients were nodular sclerosis subtype (41% vs. 66%), large mediastinal mass (9% vs. 20%), bulky disease (49% vs. 60%) and Karnofski index & lt;8, (11% vs. 3%). Acute toxicity during chemotherapy was higher in elderly patients (87% vs 79%). The most obvious differences were observed for infections (17% vs 6%). The significantly higher rate of infections was due to more severe leukopenia in elderly patients (grade IV: 41% vs 25%). As a result, significantly fewer elderly patients received at least 85% of intended chemotherapy dose (74% vs. 90%). At a median follow-up of 65 months, 38% and 11% of patients respectively died. The survival analysis showed a statistically significant poorer prognosis for elderly patients in terms of 5-year OS (65% vs. 90%), FFTF (60% vs. 79%) and Hodgkin-specific FFTF (73% vs. 82%). Conclusion: Elderly patients have a poorer risk profile compared to 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 Hodgkin lymphoma patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2670-2670
    Abstract: Introduction: Whether adolescent (alc) patients with HL represent a distinct patient group, requiring a therapy strategy separated from adults, is currently focussed in international debates. Most study groups are treating adult (ad) patients (pts) (age 〉 18 years) apart from younger patients (age 〈 18 years), considering a difference in treatment related toxicity and therapy outcome in both patient groups. Between 1988 and 1998, the GHSG trial generations 2 (G2) and 3 (G3) included younger patients from the age of 15 (G2), and 16 (G3), in identically therapy regimen with adults up to 65, and 75 years. The trials for early stages HD were comparing radiation therapy (RX) arms only (HD4, recruited 1988–1993), and, RX vs 2 cycles polychemotherapy plus RX (HD7, 1993–1998). Intermediate stages HD received 2 cycles of different chemotherapy regimen plus identically RX (HD5, 1988–1993), and, 2 identically cycles of chemotherapy plus different RX (HD8, 1993–1998). Advanced stages HL were treated with either 4 cycles conventional polychemotherapy plus EF, or, 4 cycles of a hybrid regimen plus EF RX (HD6, 1988–1993); the following trial (HD9, 1993–1998) compared 3 arms of different polychemotherapy followed by RX on bulky disease. Methods: In G2 and G3, a total of 573 adolescents (15–21 yrs) in early, intermediate, and advanced stages HL were compared with 4917 pts (15–75 yrs) for complete remission rate (CR), 5 yrs survival rate (SV), 5 yrs freedom from treatment failure (FFTF), and, secondary neoplasias (2nd NPL). (table 1) Conclusion: Based on this large analysis of HL patients treated in prospectively randomized trials, the prognosis of patients aged 15–21 years is rather similar to the prognosis of adult patients. A more detailed evaluation including age-adapted prognosis will be presented. Results: Adolescents /Adults CR % 5 yrs FFTF % 5 yrs SV % Alc Ad Alc Ad Alc Ad Early stages HD4 97.7 97.3 81.6 80.5 97.6 95.1 HD7 93.3 94.3 82.0 83.3 100 94.1 Intermediate stages HD5 93.5 93.4 83.3 81.7 94.3 90.5 HD8 93.8 92.6 84.5 82.7 97.3 91.3 Advanced stages HD6 77.8 77.0 61.0 58.8 85.3 78.6 HD9 93.5 90.3 85.8 79.2 92.4 88.0
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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