Moderate dose escalation using BEACOPP(baseline) did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.

In patients age ≥ 60 years with HL, four cycles of ABVD is associated with substantial dose reduction, treatment delay, toxicity, and treatment-related mortality.

Approximately 20% of all Hodgkin lymphoma (HL) patients are older than 60 years and have a poor prognosis, mainly because of increased treatmentrelated toxicity resulting in reduced overall dose intensity and more treatmentrelated mortality. To possibly improve the treatment of elderly HL patients, the German Hodgkin Study Group developed a new regimen, PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine). In this multicenter phase 2 study, elderly HL patients in early unfavorable and advanced stages received 6 to 8 cycles of PVAG and additional radiotherapy if they were not in complete remission (CR) after chemotherapy. Endpoints included feasibility, acute toxicity, and response rate. Fifty-nine patients 60 to 75 years of age (median, 68 years) were eligible for analysis; 93% had advanced stage disease. WHO grade 3/4 toxicities were documented in 43 patients; 46 patients responded with CR/CR uncertain (78%). Within 37 months median observation time, 15 progressions or relapses and 17 deaths were observed, of which 8 were related to HL and 1 was the result of treatment-related toxicity. The 3-year estimates for overall survival and progression-free survival were 66% (95% CI, 50%-78%) and 58% (95% CI, 43%-71%), respectively. We conclude that PVAG is safe and feasible in elderly HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00147875. (Blood. 2011;118(24): 6292-6298)

Background:Health-related quality of life (HRQoL) comprises different domains of physical, mental, and social well-being. In this analysis, we focus on sexual quality of life in Hodgkin Lymphoma (HL) patients.Methods:Four-thousand one-hundred and sixty patients enroled in the HD10–HD12 trials underwent HRQoL assessment. Instruments included the Quality of Life Questionnaire for survivors (QLQ-S), combining the European Organisation for Research and Treatment of Cancer QLQ-C30, Multidimensional fatigue (FA) inventory (MFI-20) and an additional sexual functioning (SX) scale. We describe SX up to 27 months after therapy and analyse relationship to stage, age, gender, FA, social functioning, and therapy. Statistical methods range from descriptive statistics to a classification of SX courses, and a longitudinal structural equations model with full information maximum likelihood estimation of missing data. In the analysis, a score below 50 was used to describe severe sexual dysfunction.Results:Three-thousand two-hundred and eight patients provided data on SX. Patients in advanced stages reported lower SX than patients in early stages both, before and after the treatment. During follow-up, an improvement of SX compared with baseline was detected, except for those ⩾50 years. Patients in early stages reached normal SX, whereas advanced-stage patients remained below the reference value for healthy controls. Sexual functioning during follow-up was significantly and strongly related to previous SX, other HRQoL measures, age, and stage, and to lesser degree with gender and chemotherapy.Conclusion:Overall, HL patients have a decreased sexual quality of life at baseline, which improves after therapy and normalises in early-stage patients. Importantly, long-term SX is more closely related to patient characteristics and SX at baseline than to the intensity of treatment.

Summary The outcome of patients with Hodgkin lymphoma (HL) has dramatically improved over the past decades and continues to improve with the development of novel targeted therapies, such as the immunoconjugate brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab. Moreover, with the use of response‐adapted strategies using positron‐emission‐tomography (PET), the overall intensity of treatment for most patients can be reduced, resulting in less acute and late toxicity. However, these advances are mainly restricted to younger patients, as advances in patients above the age of 60 years (‘older’ patients) have been much less pronounced. Furthermore, about one third of all HL patients are among the older population, but only 5–10% of the patients treated in current HL clinical trials are ≥60 years old. HL in older patients is characterized by aggressive disease and unfavourable prognostic features as B symptoms and predominance of advanced stages. In addition, tolerance to curative chemotherapy is drastically reduced in older patients resulting in excessive toxicity and insufficient treatment due to therapy delays and dose reductions. Therefore, there is a significant unmet medical need in older HL patients for less toxic and effective therapies, and an important gap of knowledge concerning this growing population of patients. Recent advances on epidemiology, characteristics and treatment of older HL patients will be summarized in this article.

No abstract

As part of an ivermectin dose-ranging study of onchocerciasis patients in Togo, 55 onchocerciasis patients with concomitant mansonelliasis received single oral doses either of ivermectin (100 to 200 micrograms/kg body weight) or placebo. As expected, Onchocerca volvulus microfilariae in the skin were greatly reduced in number soon after drug treatment, but microfilariae of Mansonella perstans reacted differently. Microfilarial densities of M. perstans were assessed with a filtration technique both before, and 4 times after, treatment. In untreated patients microfilarial densities were stable until the end of the study at 6 months. In patients receiving ivermectin, microfilarial densities dropped on average to less than 60% of the pre-treatment level and remained there until the final post-treatment examination. This partial reduction was probably not caused by a microfilaricidal effect of ivermectin, but rather by an altered distribution of microfilariae in the peripheral blood and in a suspected microfilarial reservoir.

INTRODUCTION A cohort study from the United States showed that Hodgkin Lymphoma patients in the SEER database had more than two times the risk of suicide compared to the general US population (J Clin Oncol 2008 26:4731-38). However, the risk of suicide in Hodgkin Lymphoma has not been studied in European clinical trial patients where treatment and disease specific information was available. METHODS Patients from the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed to identify those patients with Hodgkin Lymphoma whose cause of death was suicide. 12,201 patients from Germany, Switzerland, the Netherlands, the Czech Republic, and Austria were included in the analysis of the GHSG HD7-HD15 studies between 1993 and 2009. Median follow-up in these studies was 67.6 months or 5.63 years. Standardized mortality ratio (SMR) for death from suicide was calculated using the general European population as a control. Suicide as a cause of death was compared to other causes of death in the HD7-HD15 studies. Data from other European HL studies was planned to be included but not available at time of submission. RESULTS 19 patients (17 males and 2 females) died by suicide in the HD7-HD15 studies during a total observation time of 68,638 person-years, equivalent to 27.7/100,000 person-years. When compared to the suicide rate in the general European population of 12.3/100,000 person-years (Eurostat Statistics Database 2010), the standardized mortality ratio (SMR) in this cohort was 2.25 (95% CI, 1.40 to 3.45) and statistically significant (p=0.0017). Male gender is an established risk factor for suicide in the general population. Male and female suicide rates in the general European population were 20.7/100,000 and 4.7/100,000 person-years (Eurostat 2010) respectively. Male European HD7-HD15 patients had a suicide rate of 43.9/100,000 person-years with a SMR 2.12 (95% CI, 1.28 to 3.33), p=0.0054. Female European HD7-HD15 clinical trial patients had a suicide rate of 6.7/100,000 person-years with a SMR 1.43 (95% CI, 0.24 to 4.72), p=0.575. Median age at diagnosis was 38 years (range 19-59) for the HL patients with suicide. Median time interval between diagnosis of HL and suicide was 42 months (range 1-142), and median age at time of suicide was 46 years (range 22-59). Nodular sclerosis (58%) and mixed cellularity (26%) were the most common HL histologic subtypes in patients with suicide. As defined by the GHSG, advanced stage HL (42%) was the most common in suicide followed by early stage favorable (37%) and early stage unfavorable (21%). 74% of HL patients with suicide received radiation therapy at a median dose of 30 Gy, with 58% receiving involved-field radiation therapy (IFRT) and 16% extended-field radiation therapy (EFRT). All patients with suicide received chemotherapy (median 4 cycles), with ABVD (32%), COPP/ABVD (16%), escalated-dose BEACOPP (16%), and escalated-dose followed by baseline-dose BEACOPP (16%) as the most common regimens. 17 of 19 patients (90%) were in remission with no evidence of progression or relapsed HL at time of suicide. One patient developed a secondary malignancy (melanoma) prior to death from suicide. There were a total of 818 deaths (6.7%) in the 12,201 patients analyzed in the HD7-HD15 studies. Suicide (2.3%) was the fifth most common cause of death after Hodgkin Lymphoma (29.6%), toxicity from treatment (primary, salvage, and infection = 24.8%), secondary malignancy (21.1%), and cardiopulmonary causes (10.1%). Figure 1. CONCLUSIONS Hodgkin Lymphoma patients treated within clinical trials in Europe have greater than twice the incidence of suicide, SMR 2.25, compared to the general population. This is similar to the SMR 2.07 reported in HL patients from the SEER database in the United States. This increase in suicide incidence is in spite of the excellent prognosis in HL, as evidenced by the 90% of patients who were in remission at time of suicide. Male European HL clinical trial patients had over twice the risk of suicide compared to males in the general population, but there was no statistically significant difference found in female European HL patients. With HL occurring most frequently in age groups with a high risk of suicide, clinicians must be vigilant about suicide as a significant cause of death in these patients. Figure 1 Causes of Mortality in HD7-HD15 studies. Figure 1. Causes of Mortality in HD7-HD15 studies. Disclosures Engert: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. LaCasce:Seattle Genetics: Research Funding; Forty Seven Inc.: Consultancy.