ABVD in Older Patients With Early-Stage Hodgkin Lymphoma Treated Within the German Hodgkin Study Group HD10 and HD11 Trials

2013 ◽  
Vol 31 (12) ◽  
pp. 1522-1529 ◽  
Author(s):  
Boris Böll ◽  
Helen Görgen ◽  
Michael Fuchs ◽  
Annette Pluetschow ◽  
Hans Theodor Eich ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Early Stage ◽  
Dose Intensity ◽  
Study Group ◽  
Who Grade ◽  
Younger Patients ◽  
German Hodgkin Study Group ◽  
Treatment Related Mortality ◽  
Related Mortality

Purpose Older patients with Hodgkin lymphoma (HL) account for approximately 20% of all HL patients. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy is regarded as standard of care in these patients. However, little is known on feasibility and efficacy of ABVD in this age group. Patients and Methods We analyzed the feasibility and efficacy of four cycles of ABVD in older patients age 60 to 75 years with early-stage HL who were treated within the German Hodgkin Study Group (GHSG) HD10 and HD11 trials; results were compared with those of younger patients treated within these trials. Results In total, 1,299 patients received four cycles of ABVD, and 117 of those patients were older than age 60 years (median, 65 years). In 14% of older patients, treatment was not administered according to protocol, mainly because of excessive toxicity. The mean delay of treatment was twice as high in the older patients (2.2 v 1.2 weeks). Fifty-nine percent of older patients achieved a relative dose-intensity of at least 80% compared with 85% of younger patients. Major toxicity (WHO grade 3 and 4), including leucopenia, nausea, infection, and others, was documented in 68% of older patients with a treatment-related mortality of 5%. Complete response was achieved in 89% of older patients, 3% had progressive disease, and 11% relapsed. At a median observation time of 92 months, 28% of the patients had died, and the 5-year progression-free survival estimate was 75% (95% CI, 66% to 82%). Conclusion In patients age ≥ 60 years with HL, four cycles of ABVD is associated with substantial dose reduction, treatment delay, toxicity, and treatment-related mortality.

Treatment-Related Mortality in Patients With Advanced-Stage Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group

2013 ◽  
Vol 31 (22) ◽  
pp. 2819-2824 ◽  
Author(s):  
Diana Wongso ◽  
Michael Fuchs ◽  
Annette Plütschow ◽  
Beate Klimm ◽  
Stephanie Sasse ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hodgkin Lymphoma ◽  
Individual Risk ◽  
Tumor Control ◽  
Poor Performance Status ◽  
Study Group ◽  
Advanced Stage ◽  
German Hodgkin Study Group ◽  
Treatment Related Mortality ◽  
Related Mortality

Purpose The introduction of BEACOPPescalated (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPPescalated. Patients and Methods In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPPescalated-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Results Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPPescalated (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. Conclusion The individual risk of TRM associated with BEACOPPescalated can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

scholarly journals HODGKIN LYMPHOMA IN OLDER PATIENTS: AN ORPHAN DISEASE?

2014 ◽  
Vol 6 (1) ◽  
pp. e2014050 ◽  
Author(s):  
Antoine Thyss ◽  
Esma Saada ◽  
Lauris Gastaud ◽  
Frédéric Peyrade ◽  
Daniel Ré
Keyword(s):  
Hodgkin Lymphoma ◽  
Prospective Studies ◽  
Older Patients ◽  
Early Stage ◽  
The Elderly ◽  
Study Group ◽  
Advanced Stage ◽  
Early Stage Disease ◽  
Younger Patients ◽  
Stage Disease

Hodgkin Lymphoma HL ica be  cured in the large majority of younger patients, but prognosis for older patients, especially those with advanced-stage disease, has not improved substantially. The percentage of HL patients aged over 60 ranges between 15% and 35%.A minority of them is enrolled into clinical trials. HL in the elderly have some specificities: more frequent male sex, B-symptoms, advanced stage, sub diaphragmatic presentation, higher percentage of mixed cellularity, up to 50% of advanced cases associated to EBV. Very old age (>70) and comorbidities are factor of further worsening prognosis. Like in younger patients, ABVD is the most used protocol, but treatment outcome remains much inferior with more frequent, severe and sometimes specific toxicities. Few prospective studies with specific protocols are available. The main data have been published by the Italian Lymphoma Group with the VEPEMB schedule and the German Hodgkin Study Group with the PVAG regimen. Recently, the Scotland and Newcastle Lymphoma Study Group published the SHIELD program associating a prospective phase 2 trial with VEPEMB and a prospective registration of others patients. Patients over 60y with early-stage disease received three cycles plus radiotherapy and had 81% of 3-year overall survival (OS).Those with advanced-stage disease received six cycles, with 3-year OS of 66%.The role of geriatric and comorbidity assessment in the treatment’s choice for HL in the elderly is a major challenge. The combination of loss of activities of daily living combined with the age stratification more or less 70y has been shown as a simple and effective survival model. Hopes come from promising new agents like brentuximab-vedotin (BV) a novel antibody-drug conjugate. The use of TEP to adapt the combination of chemotherapy and radiotherapy according to the metabolic response could also be way for prospective studies.  

scholarly journals Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials

Blood ◽  
2016 ◽  
Vol 127 (18) ◽  
pp. 2189-2192 ◽  
Author(s):  
Boris Böll ◽  
Helen Goergen ◽  
Karolin Behringer ◽  
Paul J. Bröckelmann ◽  
Felicitas Hitz ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Lung Toxicity ◽  
Study Group ◽  
German Hodgkin Study Group ◽  
Key Points

Key Points Two cycles of ABVD or AVD were equally tolerable in older early-stage favorable HL patients. Excessive toxicity including severe bleomycin-induced lung toxicity occurred in older HL patients receiving 4 cycles of ABVD.

Delivery and Toxicity of Fludarabine-Based Combination Chemotherapy Regimens in Older Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3329-3329
Author(s):  
Mark N. Polizzotto ◽  
Constantine S. Tam ◽  
Henry Januszewicz ◽  
Miles Prince ◽  
Max Wolf ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Older Patients ◽  
Age Groups ◽  
Infectious Complications ◽  
P Values ◽  
Younger Patients ◽  
Severe Infections ◽  
The Difference ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Fludarabine (F)-based combination chemotherapy regimens are highly effective in a range of indolent lymphoproliferative disorders. Despite the prevalence of such disorders in older patients, the deliverability of these regimes in patients aged >= 60 has not been assessed. We analysed the delivery and toxicity of three F-based regimens, all using F 25 mg/m2/dx3 q28d, in 82 adults aged >= 60 years, and compared this with the same regimens in 99 adults aged < 60. The sample comprised 66 patients (32 >= 60) treated with F and cyclophosphamide (C; 250 mg/m2/dx3); 29 with F and mitoxantrone (M; 10 mg/m2 x1; 12 >= 60); and 86 with FC and rituximab (R; 375 mg/m2 x1; 38 >= 60). 349 cycles in older patients were compared with 393 cycles in younger patients for haematologic nadirs, infectious complications and organ toxicity. Both groups received a median of 4 cycles, although older patients were more likely to require dose reduction (4.3% of cycles versus 1.2%, P < 0.001) and growth factor support (3.8% versus 1.8%, P=0.01). The cohorts were well matched for baseline characteristics other than age. Overall, older patients had a slightly higher rate of infections (18%/cycle versus 15%/cycle), though this was not statistically significant (P = 0.28). For severe (grade >=3) infections the difference was minimal: 6% versus 7% (P< 0.5). The rates of neutropenia < 1.0 and 0.5 were 13% and 22% versus 11% and 20% for older and younger patients, respectively (all P values>0.1). The rates of thrombocytopenia < 100 and < 50 were 21% and 5% versus 16% and 5% for older and younger cohorts (all P values < 0.1). Other organ toxicities were uncommon, and showed no difference between age groups. Treatment-related mortality in both cohorts was <1% (P > 0.5). Comparison within the cohort aged over 60 showed that those aged 70 and over were at higher risk of haematological and infectious toxicity. 82 cycles delivered to 23 patients aged >= 70 were compared with 267 cycles delivered to 61 patients aged 60 to 69. The rate of infection for those over 70 was 25% versus 16% in those aged 60 to 69, though this was not statistically significant (P=0.07). For severe infections (grade >=3), the rates were 13% versus 6% (P=0.03), while rates of neutropenia < 0.5 and thrombocytopenia < 50 were 32% and 15% versus 8% and 3% for those >= 70 and 60 to 69 respectively (all P values > 0.001). These results demonstrate that F-based regimens are well tolerated and can safely be delivered to most older patients, with a modestly increased rate of infectious morbidity, but no increased treatment-related mortality. However, for patients aged >=70 the increased rate of toxicity mandates careful patient selection and monitoring.

Doxorubicin, Vinblastine and Dacarbazine with or without Bleomycin for Older Patients with Early Stage Favorable Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 Trials

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3062-3062 ◽  
Author(s):  
Boris Böll ◽  
Karolin Behringer ◽  
Helen Görgen ◽  
Paul Bröckelmann ◽  
Bastian von Tresckow ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Research Funding ◽  
Early Stage ◽  
Dose Intensity ◽  
High Rate ◽  
Equal Distribution ◽  
To Receive ◽  
Grade Iii

Abstract Introduction Bleomycin is commonly omitted from the ABVD regimen (doxorubicine, vinblastine, dacarbazine and bleomycin) in older Hodgkin Lymphoma (HL) patients due to excessive toxicity, particularly bleomycin-induced lung toxicity (BLT). Very recently, however, the GHSG HD13 trial indicated that the omission of bleomycin from the ABVD regimen has a negative impact on efficacy (Behringer et al., EHA 2014). Given the high rate of BLT in older patients, the role of bleomycin in the ABVD regimen for this particular group of patients is still unclear. We therefore analyzed feasibility, toxicity and efficacy of ABVD or AVD in 287 older early stage favorable HL patients. Methods As described in detail previously elsewhere, HD10 and HD13 were prospective, randomized international multicenter trials including early stage favorable HL patients defined as stages I and II without any of the GHSG risk factors (Engert et al. NEJM 2010). For the present study, we focused on older HL patients (≥60 years), who were randomized to receive either 2 cycles ABVD (2 x ABVD) or AVD, in both cases followed by either 20 or 30 Gy involved-field radiotherapy (IF-RT). To estimate cumulative BLT, we also analyzed older HL patients who received 4 x ABVD followed by IF-RT in the HD10 trial. Results 287 patients with a median age of 65 years (range 60-75) were included with an equal distribution of gender, IPS scores, histology and age between the treatment groups. Treatment consisted of 2 x ABVD in 137 patients (HD10 and HD13), 2 x AVD in 82 patients (HD13), and 4 x ABVD in 68 patients (HD10). Pulmonary function test (PFT) prior to therapy was available for 117 patients (HD13 only) showing impaired PF in 14 (26%) and 9 (15%) of the patients randomized to receive ABVD or AVD, respectively. Although patient numbers were too small to draw statistically sound conclusions, in our analysis, patients treated with AVD tended to receive higher relative dose intensity than patients treated with 2 x ABVD. Early termination of chemotherapy was only observed in 1 patient of each treatment arm. Overall, frequency of grade III-IV adverse events was similar for both patient groups. Respiratory adverse events were rare even in patients receiving 2 cycles of bleomycin (1 and 0 cases with 2 x ABVD and AVD, respectively). However, BLT occurred in 6 patients (9%) receiving 4 cycles ABVD and was lethal in half of the affected patients. PFTs or (chest x-ray) within two years after therapy were available for 80 HD13 patients and showed pathological results for 2 patients each out of 34 and 46 patients treated with 2 x ABVD or AVD, respectively. Regarding the efficacy, patient numbers were far too small for testing on (non-)inferiority of the AVD regimen as done in the HD13 trial. However, differences in PFS and OS were about the same magnitude as observed in the HD13 trial (Behringer et al., submitted), indicating that the effect of bleomycin on efficacy observed in this trial does also hold true for the subgroup of older patients. Conclusion In this study of 219 older early stage favorable HL patients treated with 2 cycles of either ABVD or AVD, no significant effect of bleomycin on the incidence and severity of adverse events was detectable. In contrast, the additional 67 older patients receiving 4 x ABVD had more grade III/IV toxicity and a strikingly higher rate of BLT, indicating a cumulative toxicity of bleomycin in older HL patients. Disclosures Off Label Use: Everolimus in relapsed or refractory Hodgkin Lymphoma. von Tresckow:Novartis: Honoraria, Research Funding; Takeda: Honoraria, Travel grants, Travel grants Other. Borchmann:Takeda: Honoraria, Research Funding, Travel grants Other.

Outcome of Patients With Early-Stage Infradiaphragmatic Hodgkin Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group

2018 ◽  
Vol 36 (25) ◽  
pp. 2603-2611 ◽  
Author(s):  
Stephanie Sasse ◽  
Helen Goergen ◽  
Annette Plütschow ◽  
Boris Böll ◽  
Dennis A. Eichenauer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Risk Factor ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Significant Risk ◽  
Combined Modality Treatment ◽  
Study Group ◽  
German Hodgkin Study Group ◽  
Multivariable Analyses ◽  
Clinical Trial Information

Purpose The prognostic effect of isolated infradiaphragmatic involvement in Hodgkin lymphoma (HL) is controversial, and there are little data about patients treated with current therapies. Therefore, we performed a risk factor analysis to focus on isolated nodal infradiaphragmatic disease in patients treated within the German Hodgkin Study Group trials HD13 (clinical trial information: ISRCTN63474366) and HD14 (clinical trial information: ISRCTN04761296) for early-stage HL. Patients and Methods Characteristics and outcomes of patients who had infradiaphragmatic HL were compared with patients who had supradiaphragmatic disease. Progression-free survival (PFS) and overall survival (OS) were estimated according to Kaplan-Meier methods and were compared between groups using the log-rank test and Cox proportional hazards regression, which was also applied for multivariable analyses that adjusted for relevant baseline characteristics. Results Of 2,903 qualified patients, 223 (7.7%) were diagnosed with isolated nodal infradiaphragmatic disease. In general, these patients were older, had a poorer performance status, were more often male, and had the nodular sclerosis subtype less often than those with supradiaphragmatic disease. After a median follow-up time of 51 months, PFS and OS were significantly worse in patients with infradiaphragmatic disease (5-year PFS and OS, 80.1% and 91.5% v 91.2% and 97.6% in patients with supradiaphragmatic disease; each P < .001). In multivariable analyses, infradiaphragmatic HL remained a significant risk factor in terms of PFS (hazard ratio [HR], 1.5; 95% CI, 1.04 to 2.2; P = .03) and OS (HR, 2.0; 95% CI, 1.2 to 3.5; P = .01). However, inferior PFS and OS could not be observed among those patients treated with the more intensive chemotherapy (two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] in HD13, and two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPPescalated] plus two cycles of ABVD in HD14; all patients received 30 Gy of involved-field radiotherapy). Conclusion Early-stage HL that presents with infradiaphragmatic disease only represents a distinct patient group with an inferior outcome. However, this adverse outcome can be outweighed by appropriate combined modality treatment.

Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials

2017 ◽  
Vol 35 (13) ◽  
pp. 1444-1450 ◽  
Author(s):  
Paul J. Bröckelmann ◽  
Helen Goergen ◽  
Charlotte Kohnhorst ◽  
Bastian von Tresckow ◽  
Alden Moccia ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Observation Time ◽  
Hazard Ratio ◽  
Late Relapse ◽  
German Population ◽  
Study Group ◽  
Adequate Treatment ◽  
German Hodgkin Study Group ◽  
First Diagnosis

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.

scholarly journals Gonadal Function and Fertility in Survivors After Hodgkin Lymphoma Treatment Within the German Hodgkin Study Group HD13 to HD15 Trials

2013 ◽  
Vol 31 (2) ◽  
pp. 231-239 ◽  
Author(s):  
Karolin Behringer ◽  
Horst Mueller ◽  
Helen Goergen ◽  
Indra Thielen ◽  
Angelika Diana Eibl ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Hodgkin Lymphoma ◽  
Recovery Time ◽  
Early Stage ◽  
Study Group ◽  
Advanced Stage ◽  
Male Survivors ◽  
German Hodgkin Study Group ◽  
The Impact

Purpose To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL. Patients and Methods Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated. Results A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism. Conclusion The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.

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