Concurrence of inflammatory bowel disease with multiple sclerosis or Hodgkin lymphoma.

BACKGROUND AND AIMS: Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn's disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients. METHODS: All patients with HL, MS, CD, or UC were identified in the veterans population from 2016-2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15-1.71) and MS (1.34, 1.19-1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07-3.17) and MS (2.31, 1.59-3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant. CONCLUSION: The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.

Brentuximab vedotin plus AVD for Hodgkin lymphoma: incidence and management of peripheral neuropathy in a multisite cohort.

Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.

Modern Management of Anthracycline-Induced Cardiotoxicity in Lymphoma Patients: Low Occurrence of Cardiotoxicity with Comprehensive Assessment and Tailored Substitution by Nonpegylated Liposomal Doxorubicin.

BACKGROUND: Anthracyclines (AC) are still undeniable drugs in lymphoma treatment, despite occasionally causing cardiotoxicity. Liposomal AC may reduce cardiotoxicity while retaining clinical efficacy; also, biomarker monitoring during chemotherapy allows early detection of cardiac damage, enabling strategies to prevent left ventricular ejection fraction (LVEF) deterioration. MATERIALS AND METHODS: We conducted a prospective observational trial in a real-life population of lymphoma patients, combining advanced echocardiography and biomarkers (Troponin I [TnI]) for early detection of cardiotoxicity; we applied a prespecified policy to minimize cardiotoxicity, selecting patients with higher baseline risk to replace doxorubicin with nonpegylated liposomal doxorubicin (NPLD) and starting cardioprotective treatment when subclinical cardiotoxicity was detected. RESULTS: Ninety-nine patients received ≥1 cycle of chemotherapy (39 with NPLD): 38 (NPLD = 34) were older than 65 years. At baseline, the NPLD subgroup had more cardiovascular risk factors and comorbidities than the doxorubicin subgroup. After treatment, echocardiographic parameters did not worsen in the NPLD subgroup; significant LVEF reduction occurred in two patients treated with doxorubicin. Over treatment course, TnI rises increased linearly in the doxorubicin subgroup but modestly in the NPLD subgroup. At doxorubicin doses >200 mg/m2 the difference was statistically significant, with more TnI rises in the doxorubicin subgroup. NPLD-treated patients did not experience higher rates of grade 3-4 adverse events. Within the diffuse large B-cell lymphomas category, we observed similar rates of complete and overall responses between doxorubicin- and NPLD-treated patients. CONCLUSION: A comprehensive strategy to prevent, detect, and treat cardiotoxicity allows an optimal management of the lymphoma with low incidence of cardiac complications. The Oncologist 2017;22:422-431 IMPLICATIONS FOR PRACTICE: Despite the recent advances of targeted therapy in cancer, old cytotoxic drugs such as anthracyclines (AC) still play a fundamental role in the treatment of many lymphoma patients. We tested and validated in a real-life setting a personalized approach to prevent, detect, and treat AC-induced cardiotoxicity; biomarker monitoring was accomplished by Troponin I measurements before and after chemotherapy infusions, allowing detection of early subclinical cardiotoxicity, which was preemptively treated with cardio-protectants (beta blockers and angiotensin-converting-enzyme inhibitors). A telemedicine system allowed interdisciplinary management of the patients with an expert cardiologist. Furthermore, tailored use of liposomal AC following a prespecified policy appeared to prevent the excess cardiotoxicity expected in high-risk patients.

Assessment of Valvular Disorders in Survivors of Hodgkin's Lymphoma Treated by Mediastinal Radiotherapy ± Chemotherapy.

As the number of Hodgkin's lymphoma (HL) survivors grows, understanding long-term complications becomes more important. Mediastinal radiotherapy (MRT) seems to cause valvular disease, and the prevalence might increase during follow-up. In this cross-sectional study 82 HL survivors participated (52% men, mean age 47.8 years, 50 treated with MRT). Valvular disease was diagnosed by transthoracic echocardiography and compared between HL survivors treated with and without MRT. Univariate and multivariate logistic regression analysis was used to identify predictors for valvular disease. During a median follow-up of 13.4 years (range 2 to 39 years), ≥ mild valvular disease was present in 61.2% of HL survivors with MRT (n = 30), compared with 31.0% of HL survivors without MRT (n = 9; odds ratio [OR] 3.51, 95% CI 1.32 to 9.30, p = 0.01). In multivariate analysis, only current age remained predictive for ≥ mild valvular disease (OR 1.08 per year, 95% CI 1.01 to 1.14, p = 0.023). Aortic regurgitation (AR) was most prevalent and irradiated patients had significantly more ≥ mild AR (38.2% vs 6.8%, p = 0.007). Within the MRT subgroup, time after radiation of >15 years was associated with AR (OR 4.70, 95% CI 1.05 to 21.03, p = 0.043), after adjusting for current age and hypertension. Severe valvular disease was present in 24.5% of HL survivors with MRT compared with 3.4% without MRT (p = 0.016). Valvular surgery was performed in 9 HL survivors (18.0%) with MRT and in none without MRT. In conclusion, the prevalence of valvular disease in HL survivors treated with MRT is high and increases with time after irradiation. Long-time screening for valvular disease by transthoracic echocardiography might be worthwhile.

Wage-subsidised employment as a result of permanently reduced work capacity in a nationwide cohort of patients diagnosed with haematological malignancies.

BACKGROUND: Patients with haematological malignancies have a poorer labour market prognosis than the general population. We have previously found that they have low rates of return to work, and a higher risk of being granted disability pension, than individuals without a history of these diseases. The aim of this study was to further investigate the labour market prognosis for these patients, by comparing the risk of being granted wage-subsidised (WS) employment as a result of permanently reduced work capacity among patients diagnosed with haematological malignancies to a reference cohort, and to determine if relative risks differ between subtypes of haematological malignancies. MATERIAL AND METHODS: We combined data from national registers on Danish patients diagnosed with haematological malignancies between 2000 and 2007 and a reference cohort without a history of these diseases. A total of 3194 patients and 28 627 reference individuals were followed until they were granted WS employment, disability pension, anticipatory pension, old age pension, emigration, death or until 26 February 2012, whichever came first. RESULTS: A total of 310 (10%) patients and 795 (3%) reference individuals had their work capacity permanently reduced to an extent that they were granted WS employment during the follow-up period. Age- and gender-adjusted relative risks differed significantly between the subgroups of haematological malignancies, and four years after diagnosis they ranged from 2.47 (95% CI 1.46-4.16) for patients with Hodgkin lymphoma to 10.83 (95% CI 7.15-16.40) for patients with chronic myeloid leukaemia. CONCLUSION: All eight subtypes of haematological malignancies were associated with an increased risk of being granted WS employment due to permanently reduced work capacity compared to the reference cohort. The relative risks differed according to haematological malignancy subtype, and the highest was found for patients with chronic myeloid leukaemia.

Granulocyte colony-stimulating factor as secondary prophylaxis of febrile neutropenia in the management of advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy: a decision analysis.

Current practice guidelines are unclear regarding the role of secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma despite several small retrospective studies that demonstrate the omission of growth factors to be a safe and economic practice. We used a decision-analytic model to compare secondary prophylaxis with granulocyte colony-stimulating factor (G-CSF) to no G-CSF with the onset of severe neutropenia for a hypothetical cohort of patients with advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). There was a net benefit of 0.017 years and 0.037 quality-adjusted life years for no G-CSF use in severe neutropenia. On microsimulation (10 000 trials), 96% of the simulations showed that the no G-CSF strategy is preferred to the use of G-CSF. This finding was robust across a wide range of sensitivity analyses. Our analysis suggests that G-CSF not be used as secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma.

Health care use of long-term survivors of childhood cancer: the British Childhood Cancer Survivor Study.

PURPOSE: Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors. METHODS: We used data from the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving ≥ 5 years. Frequency of talks to a doctor, hospital outpatient visits, and day-patient and inpatient hospitalizations were ascertained by questionnaire in 10,483 survivors and were compared with the General Household Survey 2002 data by using logistic regression. RESULTS: Among survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended the outpatient department of a hospital in the last 3 months, 11.9% had been hospitalized as a day patient in the last 12 months, and 9.8% had been hospitalized as an inpatient in the last 12 months. Survivors had talked slightly more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI, 1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95% CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for outpatient and inpatient care. The OR of health care use did not vary significantly with age of survivor. CONCLUSION: We have quantified how excess morbidity experienced by survivors of childhood cancer translates into increased use of health care facilities.

Disease patterns in pediatric classical Hodgkin lymphoma: a report from a developing area in Brazil.

Epidemiological patterns established about 20 years ago, divided classical Hodgkin lymphoma (cHL) in three entities with regard to Epstein-Barr virus (EBV) status and histological subtypes and suggested different epidemiological patterns associated with degree of economic development. Here, we investigated histopathological features and EBV association in 100 consecutive pediatric cHL cases occurring in Rio de Janeiro (Brazil). Age at diagnosis ranged from 3 to 18 years (median 14 years) with 27% of cases ≤10 years. Unexpectedly, we did not observe an early childhood peak with most cases occurring in the >10 years age group. Nodular sclerosis (NS) was the most frequent subtype (69%) and was more frequently observed in the >10 years age group, followed by mixed cellularity (MC, 23%) which was distributed equally between age groups. EBV was identified in 44.8% of cases, without preferential association with age groups (≤10 years vs. >10 years). MC cases were independently associated with EBV infection of tumour cells (p = 0.045) and with a CD4/CD20 ratio <1 in the microenvironment (p = 0.014). Our results suggest that a gradual shift from childhood peak to early adulthood peak may be observed in developing regions. The development of MC subtype may result from early exposure to EBV in the context of an impaired immune system reflected by a CD4/CD20 ratio <1. Conversely, it is possible that NS originates predominantly in the context of a better immune response against EBV and/or tumour antigens expressed in the neoplastic cells.

Isolated neutropenia during ABVD chemotherapy for Hodgkin lymphoma does not require growth factor support.

We reviewed the outcome of 24 patients with early and advanced stage Hodgkin lymphoma (HL) treated with ABVD chemotherapy (263 treatment deliveries) without the use of G-CSF over a 3-year period. Patients received full dose ABVD regardless of the absolute neutrophil count (ANC) on the day of treatment if there were no other cytopenias or toxicities. Forty-eight percent of treatment deliveries were given with an ANC <1.0 x 10(9)/L and 18% with an ANC <0.5 x 10(9)/L. Four patients required drug omissions (vinblastine or bleomycin) due to non-hematological side-effects. The rate of neutropenic sepsis was 0.76%. At a median follow up of 17.5 months, one patient had progressive disease requiring intensive treatment and the remainder were in remission post-treatment. Overall survival and event-free survival were 95.8% and 91.7%, respectively. We estimate a saving of 60,000 pounds in pharmaceutical and nursing expenditure related to G-CSF; a saving of 2000 pounds per patient. We conclude that full dose ABVD can be administered to patients with early and advanced stage HL irrespective of isolated neutropenia on the planned treatment day without prophylactic G-CSF or antibiotics and that this practise is safe, efficacious and cost-saving.

What is the price of survival in Hodgkin's lymphoma? Long-term follow-up of cured patients.

The paper investigates the late complications of cured Hodgkin's lymphoma (HL) patients. Ninety cured HL patients between 1975 and 1994 were examined. The mean ages of patients at the time of diagnosing HL, and the median period of survival after diagnosis were 32 (11-70) years and 18 (10-30) years, respectively. Among the 90 patients, 73 are still alive, there is no information about 9 and 8 patients died, second malignant disease being the cause of death in 4 of them. Relapse was observed in 24 patients, of which 19 recovered after relapse and were included in the study then. Five patients had late relapse. In 38% of patients, cardiovascular changes, while in 32% pulmonary and pleural damages were observed. Disorders of the thyroid gland, overwhelmingly hypothyroidism, were found in 24%. Less frequently, a second malignant tumour (9%), damage to the skin, musculature, bones and genitourinary system (6%) as well as the gastrointestinal system could be detected. Treatment based on modern therapeutic approaches is expected to decrease the incidence of complications. Still the aim is early detection through close patient follow-up, which may improve the quality of life and decrease mortality as a result.

Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy.

A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas.

Ethical decision-making processes used by health care providers.

This paper reports the results of a study conducted with 18 health care providers (HCPs) in two Toronto hospitals. The study examined and assessed how these HCPs make clinical-ethical decisions in the light of a theoretical model of clinical-ethical decision making. Nine nurses and nine doctors were interviewed through two-phased, in-depth, semi-structured interviews. The results suggest that, in relation to the two major elements of the model, namely the ethical component and the decision theory component, the HCPs did not follow a consistent and systematic pattern of ethical decision making. Differences emerged between their actual self-reported behaviour and their potential more capability (i.e. their abstract thought process). The general picture that emerged was that decisions were made in a narrow, habitual manner, through the elimination of the most significant and demanding elements of the process. HCPs' ethical approaches affected the entire process of the decision making: their perception of the problem, their search for and selection of information and evidence, and their development of alternatives and resultant consequences. It is suggested to (a) further investigate and understand the subjective realities of the individuals involved in the decision making processes, their values and the meaning they ascribe to their choices, and (b) to establish extensive educational programmes to enhance HCPs' decision-making capacity and subsequently promote an effective and responsible professional practice.

Quality of life in people with Hodgkin's disease.

The diagnosis and treatment of Hodgkin's disease are not without cost in terms of both short- and long-term sequelae that have an impact on quality of life. This paper reviews quality of life in Hodgkin's disease both during and after treatment, with a focus on medical, psychosocial, and psychological functioning. In general, patients with Hodgkin's disease emerge from successful treatment significantly affected. Often, the impact of the disease and its treatment has both positive and negative aspects. Positive effects include increased appreciation for life, enhanced self-esteem and sense of personal direction, and closer family ties. Negative effects include risk of second malignancy, infertility, difficulty with intimacy and sexuality, employment discrimination, insurance discrimination, increased general distress, and fear of recurrence. The many and diverse needs of Hodgkin's disease survivors merit increased attention from the health-care delivery system.

Hodgkin's disease: is there a price for successful treatment? A 25-year experience.

Three hundred-twenty patients with Hodgkin's disease (HD) were studied retrospectively to assess the impact of treatment on survival and the development of second malignant neoplasms (SMN). All stages of HD were considered. Treatment groups included XRT only, XRT + multiagent chemotherapy (MAC), XRT + single agent chemotherapy (SAC), and chemotherapy only (Chemo). MAC was subdivided into MOPP and non-MOPP regimens. Twenty-one patients developed 23 SMN, only two of which were acute leukemias. Survival was greatest for XRT only because of a large proportion of early stage HD in this group. SMN were seen in all treatment groups except Chemo only. The XRT + MAC group had a significantly elevated observed-to-expected ratio for SMN, but it was difficult to attribute this to either MOPP or non-MOPP due to very small numbers of patients. The actuarial risk of SMN for both MOPP and non-MOPP rises dramatically between 10 and 15 years, however, extrapolation cannot be done, again because of very small numbers. We conclude that there is an increased risk of SMN in patients treated aggressively for HD, but that the exact cause of SMN is difficult to determine.

[Psychosocial repercussions of the the treatment of Hodgkin's disease. Assessment by questionnaire with 150 patients]. / Retentissement psychosocial du traitement de la maladie de Hodgkin. Appréciation par questionnaire auprès de 150 malades.

One hundred and fifty patients, treated for Hodgkin's disease (stages I-IIIA) in a cooperative trial and remaining in complete remission after 2 to 7 years, answered a questionnaire dealing with psychosocial status and quality of life. Many informations were gathered and studied by multiparametric methods. Quality of life of patients appears determined by three kinds of parameters: patients' characteristics (age, sex, family and work status); stage of the disease determining the intensity and duration of treatment; practical conditions of treatment. These last parameters may be improved by therapeutic team and all care-takers to decrease bad consequences of disease and treatment and also to increase quality of life after cure.

The cost of surviving thrombotic thrombocytopenic purpura: case report.

The neuropsychiatric sequelae of thrombotic thrombocytopenic purpura (TTP) have not been discussed previously since most patients did not survive. The affective disorder, personality change, and cognitive deficits which resulted from TTP in a 55-year-old man who had already survived stage IIIB Hodgkin's disease are described. The neurologic and psychiatric residua did not indicate a chronic form of the disease.

Amphotericin pharmacophobia.

Five cases are described in which fear of the possibly hazardous effects of giving amphotericin to patients with kidney disease resulted in death from progressive infection by an amphotericin-sensitive fungus (Cryptococcus neoformans in three cases, Blastomyces dermatitidis in one case, and Histoplasma capsulatum in one case).