Survivors Of Hodgkin's Disease Research Articles

High risk of second cancers in Hodgkin's disease survivors

High risk of second cancers in Hodgkin's disease survivors

Pneumococcal Vaccine in Patients With Absent or Dysfunctional Spleen

Four patients (3 long-term Hodgkin disease survivors and 1 recipient of an allogeneic bone marrow transplant) developed severe infections with Streptococcus pneumoniae after staging splenectomy or due to functional hyposplenism after total body irradiation and bone marrow transplantation. Current guidelines for prevention of infection recommend pneumococcal immunization for patients with Hodgkin disease treated with splenectomy and others with functional hyposplenism. Booster vaccination after 5 years is also advised. Hospital- and community-based vaccination initiatives may help identify at-risk patients.

Comparing thyroid ultrasonography to thyroid function in long‐term survivors of childhood lymphoma

We studied the value of thyroid ultrasonography as a follow-up tool in survivors of childhood lymphomas and correlated morphologic abnormalities with thyroid function tests. A prospective follow-up study of 45 long-term survivors of histology-proved childhood lymphomas was performed. Mean age at diagnosis was 9.1 years (range 2.1-16.4 years) and mean follow-up duration 10.9 years (range 3.9-22.2 years). Among the 26 survivors of Hodgkin disease (HD) who received mantle field irradiation, 14 (54%) had abnormal ultrasonograms. Elevated thyroid-stimulating hormone (TSH) concentrations were found in 14 (54%), and 6 of them (42%) had normal thyroid functions. Six of twelve patients with normal ultrasonograms had abnormal thyroid function, and 5 of 11 patients with normal function had abnormal sonograms. Among the 19 non-HD survivors who did not receive radiotherapy, 18 (95%) had both normal sonograms and normal function. Thus thyroid gland abnormalities were detected in 54% of HD survivors after mantle field irradiation. No correlation between the abnormalities detected on ultrasonography and serum levels of TSH and thyroid hormones were found. Both ultrasound and thyroid function tests independently provide clinically useful information; the former examines gland morphologogy and the latter evaluates hormonal changes associated with thyroid disease. The high frequency of thyroid abnormalities detected by ultrasonography suggests that periodic thyroid ultrasonography is advisable in the follow-up of patients treated with mantle irradiation to screen for morphologic changes that may presage malignant transformation.

Fatigue and Psychiatric Morbidity Among Hodgkin's Disease Survivors

Fatigue is prevalent among cancer patients, including Hodgkin's disease survivors (HDS). Fatigue is poorly understood, and the clinical management is consequently difficult. This cross-sectional study examined how fatigue related to psychiatric morbidity among 457 HDS (aged 19–74 years, 56% males) treated during the period 1971–1991. The subjects were mailed a questionnaire including the Fatigue Questionnaire, the Hospital Anxiety and Depression Scale, and measures of previous psychiatric problems. Fatigue correlated moderately with anxiety and depression (r = 0.44 and 0.41 respectively). Twenty-six percent of the HDS had substantial fatigue for 6 months or longer (=cases). They had higher levels of anxiety (mean 7.3, 95% CI 6.4–8.1) and depression (mean 4.5, 95% CI 3.8–5.2) than the non-cases (anxiety: mean 4.3, 95% CI 3.9–4.7; depression: mean 2.1, 95% CI 1.8–2.5). Past psychiatric problems were not reported more commonly among the fatigue cases than among the non-cases. A multiple logistic regression analysis identified age (OR 1.04, 95% CI 1.02–1.06), anxiety (OR 1.2, 95% CI 1.2–1.3), and no self-reported psychiatric symptoms during treatment (OR 2.3, 95% CI 1.3–4.2) as predictors of fatigue caseness. One-half of the fatigue cases among HDS have psychological distress that might respond to treatment. Chronic fatigue among HDS is not predicted by previous psychiatric problems.

Comparing thyroid ultrasonography to thyroid function in long-term survivors of childhood lymphoma

We studied the value of thyroid ultrasonography as a follow-up tool in survivors of childhood lymphomas and correlated morphologic abnormalities with thyroid function tests.A prospective follow-up study of 45 long-term survivors of histology-proved childhood lymphomas was performed. Mean age at diagnosis was 9.1 years (range 2.1-16.4 years) and mean follow-up duration 10.9 years (range 3.9-22.2 years).Among the 26 survivors of Hodgkin disease (HD) who received mantle field irradiation, 14 (54%) had abnormal ultrasonograms. Elevated thyroid-stimulating hormone (TSH) concentrations were found in 14 (54%), and 6 of them (42%) had normal thyroid functions. Six of twelve patients with normal ultrasonograms had abnormal thyroid function, and 5 of 11 patients with normal function had abnormal sonograms. Among the 19 non-HD survivors who did not receive radiotherapy, 18 (95%) had both normal sonograms and normal function. Thus thyroid gland abnormalities were detected in 54% of HD survivors after mantle field irradiation. No correlation between the abnormalities detected on ultrasonography and serum levels of TSH and thyroid hormones were found.Both ultrasound and thyroid function tests independently provide clinically useful information; the former examines gland morphologogy and the latter evaluates hormonal changes associated with thyroid disease. The high frequency of thyroid abnormalities detected by ultrasonography suggests that periodic thyroid ultrasonography is advisable in the follow-up of patients treated with mantle irradiation to screen for morphologic changes that may presage malignant transformation.

Fatigue. Measures and relation to pain.

Fatigue describes reduced capacity to sustain force or power output, reduced capacity to perform multiple tasks over time and simply a subjective experience of feeling exhausted, tired, weak or having lack of energy. Pain and fatigue have several components in common, such as being subjective, prevalent in most patients with cancer and caused by multiple factors of both a physical and psychological nature. In order to explore the relationship between fatigue and pain, data from five studies were used: two random samples from the Norwegian population (n=2323 and n=1965), Hodgkin's disease survivors (n=459), palliative care patients (n=434) and patients with bone metastases (n=94). All patients had completed one or more of the following instruments: EORTC QLQ-C30, SF-36 and/or Fatigue Questionnaire. The level of fatigue was much higher in the two palliative care populations (54.4 and 63.2) as compared to the normal population samples (25.0). Patients with bone metastases had significantly more pain (72.0) than the patients in the palliative care trial (47.4) and norms (20.5). In the two palliative care and bone metastases populations fatigue was almost unchanged over time, while pain was reduced. In the palliative care population a high level of fatigue (80.3) and pain (57.8) was reported 0-1 month before death. The relationship between pain, fatigue and the health-related quality of life domains should be explored in more detail, especially in follow-up studies in order to assess possible changes over time. In addition, the validity of the existing instruments measuring fatigue should be investigated for use in patients with advanced disease and short life expectancy.

Pregnancy outcome in long-term survivors of childhood cancer.

By the year 2010, 1/250 young adults will be long-term survivors of childhood cancer. One of the major concerns is whether they will be able to have healthy children. The literature was reviewed to determine 1) the extent of intrapartum and perinatal complications experienced by survivors or their spouses and 2) the risk of congenital malformations or cancer in their children. Series have reported on pregnancy complications among approximately 400 female survivors and 300 partners of male survivors. An increased incidence of spontaneous abortions, low-birth-weight babies, and neonatal deaths has been described for women with Wilms tumor who had received at least 20 Gy abdominal radiation. Hodgkin disease survivors who had received both radiation and chemotherapy (but not either alone) also appear to be at increased risk of spontaneous abortions. Based on several thousand survivor offspring, there is no overall increased risk of either congenital malformations or childhood cancer. Further studies will define the outcome of offspring of cancer survivors treated in the modern era.

Gonadal function in young patients successfully treated for Hodgkin disease.

Gonadal function in pediatric and young adult survivors of Hodgkin disease is not very well defined. This study evaluates the outcome following the Multiple Drug Protocol (MDP) and the results are compared to the published experience. Ovarian and testicular function was assessed in 65 patients (36 males) with Hodgkin disease in first or second complete remission after treatment with either radiation (RT, n = 13), chemotherapy (CT, n = 9), or both (n = 43). Chemotherapy consisted of six cycles of the MDP (doxorubicin, procarbazine, prednisone, vincristine, and cyclophosphamide). Median age at diagnosis was 13.1 years (range, 2.4-22.6) and median age at evaluation was 22.6 years (range, 15.1-33.7), which was 6.7 years (range, 2.0-19.8) after the completion of all treatments. For the purpose of analysis, patients were divided into three groups: group A, patients who received only RT that did not include the pelvis (8 females, 5 males); group B, patients who received CT but no pelvic RT (15 females, 25 males); and group C, patients who received CT plus pelvic RT (6 females, 6 males). All patients progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25, and 5/6 and testicular volume was decreased in 1/3, 4/11, and 2/3 group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 91% and 88% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone, respectively. FSH and LH were increased in 0/8, 3/15, and 2/6 group A, B, and C female patients, respectively, at last follow-up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. Six females delivered eight normal children. The majority of males who received CT +/- RT have evidence of germ cell dysfunction, while Leydig cell function is unaffected in most. In females, although abnormal function early after the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential.

Heterozygous germline ATM mutations do not contribute to radiation-associated malignancies after Hodgkin's disease.

The successful treatment of Hodgkin's disease has been associated with an increased incidence of secondary malignancies. To investigate whether genetic factors contribute to the development of secondary tumors, we collected family cancer histories and performed mutational analysis of the ataxia-telangiectasia (AT) gene, ATM, in a cohort of Hodgkin's disease survivors with secondary malignancies. ATM was chosen for evaluation because of the increased radiosensitivity of cells derived from AT patients and obligate heterozygotes and the epidemiologic observation that AT carriers are at increased risk for radiation-induced breast cancer. Fifty-two patients who developed one or more neoplasms after treatment for Hodgkin's disease participated in this study. Personal and family histories of cancer were obtained through patient interviews and review of medical records. ATM mutational analysis was performed using a yeast-based protein truncation assay. Seventy-six secondary neoplasms were observed in this cohort of 52 Hodgkin's disease survivors, with 18 patients (35%) developing more than one secondary neoplasm. Positive family histories of cancer were present in 11 (21%) of 52 patients, compared with three (4%) of 68 Hodgkin's disease patients in a comparison cohort who did not develop secondary neoplasms (P =.008; Fisher's exact test). No germline ATM mutations were identified, resulting in an estimated AT carrier frequency in this population of 0% (90% confidence interval, 0% to 4%). Analysis of the number of tumors per individual and the family history of cancer in our cohort suggests that genetic factors may contribute to development of secondary neoplasms in a subset of Hodgkin's disease survivors. Mutational analysis, however, does not support a significant role for heterozygous truncating ATM mutations. Future studies evaluating other genes involved in DNA damage response pathways are warranted.

Reduced health-related quality of life among Hodgkin's disease survivors: A comparative study with general population norms

Late complications after curative treatment of Hodgkin's disease are of special relevance because most of the cured are young adults. The aims of the present study were: (1) to compare health-related quality of life (HRQOL) in Hodgkin's disease (HD) survivors with normative data from the general Norwegian population and (2) to examine the relations between disease/treatment characteristics and HRQOL in the HD survivors. 459 HD survivors aged 19-74 years (mean 44.0, SD 11.8) treated at the Norwegian Radium Hospital 1971-1991 were approached in 1994 and compared to norms from 2214 subjects approached in 1996. The norms are representative of the general Norwegian population. HRQOL was assessed by the Short Form 36 (SF-36), which measures HRQOL in eight separate scales (0 = worst health state, 100 = best health state). The HD survivors had lower scores than the normal controls on all scales after adjustment for age, gender and educational levels. Statistically significant differences (P < 0.01) were found in general health (10.4), physical functioning (6.1), role limitations (physical, 9.3), physical functioning (3.6) and in vitality (4.7). Patients with disease stage IB-IIB had the lowest scores on all scales. The differences in relation to stage/substage reached statistical significance (P < 0.01) in physical functioning and in role limitations (physical). Time since diagnosis, types of primary treatment or having relapsed were not associated with statistically significant differences in HRQOL. Long-term HD survivors have poorer HRQOL, primarily in physical health, than the general Norwegian population.

Hodgkin's disease survivors more fatigued than the general population.

To estimate the level of fatigue and frequency of fatigue cases among Hodgkin's disease survivors (HDS) and compare them with normative data from the general population. A cross-sectional follow-up study was done of 557 HDS (age range, 19 to 74 years) treated at the Norwegian Radium Hospital from 1971 to 1991. The sample was approached by mail, and their data were compared with normative data from 2,214 controls (age range, 19 to 74 years) representative of the general Norwegian population. Of the 557 HDS, 459 (82%) responded. The mean age (+/- SD) at the time of study was 44+/-12 years, and the mean observation time was 12+/-6 years. The Fatigue Questionnaire (11 items) measures physical and mental fatigue. Two systems of scoring were used, dichotomized (0, 0, 1, and 1) and Likert (0, 1, 2, and 3). Total fatigue (TF) constitutes the sum of all the Likert scores. Caseness was defined as a total dichotomized score of > or =4 and fatigue that lasted 6 months or longer. The HDS had significantly higher levels of TF than the controls (14.3 v 12.2) (P < .001). Fatigue among the HDS equaled that of the controls in poorest health. More HDS (61%) than controls (31%) reported fatigue symptoms lasting 6 months or longer (P < .001). Fatigue cases were more frequent among HDS (men, 24%; women, 27%) than among the controls (men, 9%; women, 12%) (P < .001). Disease stage/substage IB/IIB predicted fatigue caseness (P = .03). No significant associations were found between treatment characteristics and fatigue. Hodgkin's disease survivors are considerably more fatigued than the general population and report fatigue of a substantially longer duration.

Assessment of health status and health-related quality of life in survivors of Hodgkin's disease in childhood

Assessment of health status and health-related quality of life in survivors of Hodgkin's disease in childhood

Assessment of health status and health-related quality of life in survivors of Hodgkin's disease in childhood

Although the great majority of children with Hodgkin's disease survive with modern treatment strategies, the list of late sequelae is long, yet there is no published information on the comprehensive health status and health-related quality of life (HRQL) in this population. In the experience of a single institution, survivors of Hodgkin's disease in childhood were invited to self-report on their health status using a 15-item questionnaire connected to the Health Utilities Index, a series of multi-attribute health status classification systems that, in turn, are linked to preference functions which provide single-attribute and global utility scores for HRQL. The mean global utility score was 0.85 (on a 0 = dead to 1. 0 = perfect health scale), a figure less than that in survivors of acute lymphoblastic leukemia (ALL) but comparable to that in survivors of brain tumors (0.84) or extremely low birthweight (ELBW 0.82). The burden of morbidity is emphasized by the ratio of the numbers of health states per patient:0.67 for survivors of Hodgkin's disease, 0.66 for survivors of brain tumors, 0.39 for survivors of ELBW, 0.47 for survivors of high-risk ALL and 0.28 for survivors of standard-risk ALL. In Hodgkin's disease survivors, the attributes affected most commonly and severely were pain, cognition and emotion. This experience demands exploration of the health status and HRQL in a much larger cohort of such survivors, perhaps in the context of co-operative group studies.

Early mortality risk for paediatric Hodgkin's disease survivors

Early mortality risk for paediatric Hodgkin's disease survivors

Socio-medical situation for long-term survivors of Hodgkin’s disease: a survey of 459 patients treated at one institution

We present the socio-medical situation for 459 adult disease-free long-term survivors of Hodgkin’s disease (HD) 3–23 years after first line curative treatment. In 1994, 557 patients were sent a self-report questionnaire relating to their social status and 459 patients (82%) replied. Educational or professional plans were changed due to HD in 142 patients (32%). After 6, 12 and 18 months from start of treatment, 52, 82 and 95% of the patients, respectively, had returned to their job or education. The sum of full-time and part-time employment was in men 78% at diagnosis and 85% at follow-up, and in women 57% at diagnosis and 64% at follow-up. Only 2% of men and 3% of women did not have a job at follow-up in 1994. At diagnosis 2% of the patients were permanently disabled versus 19% at follow-up in 1994. Age >40 years at diagnosis, increased the total score of psychological distress and fatigue and long-term disablement after first line treatment were predictors for permanent disablement. Transient or permanent sexual problems were reported in 16% and 13%, respectively. MVPP (mustine, vinblastine, procarbazine and prednisone) or LVPP (chlorambucil, vinblastine, procarbazine and prednisone) chemotherapy was responsible for most cases of early menopause in women older than 30 years, and of infertility in both men and women. In summary, most long-term HD survivors had adapted well to their socio-medical situation except a high number of permanently disabled patients. By focusing more on factors predisposing for permanent disablement and early treatment for these, more patients may be helped to return to their job.

Modest decline in late mortality following Hodgkin's disease in the southeastern Netherlands since 1972.

Since prolonged remission can be induced in the majority of patients with Hodgkin's disease (HD), treatment-related mortality and morbidity have emerged. We investigated whether awareness of toxicity diminished treatment-related mortality for unselected patients treated between 1972 and 1993 in general hospitals in the southeastern Netherlands. We also estimated the prevalence of treatment-related morbidity among patients treated in the 1980s. Data were collected on all 345 HD patients registered in the Eindhoven Cancer Registry between 1972 and 1993. Medical records and histology were reviewed; follow-up ended in 1994. Administration of MOPP chemotherapy decreased, and there was a shift from total nodal irradiation to less extended low-dose radiotherapy. For cured patients the 10-year relative survival improved from 84% in the 1970s to 90% in the 1980s, which is reflected by a decline in excess mortality from 16% to 10%. The 10-year relative mortality risk due to secondary malignancies decreased from 4.3 (95% CI, 1.2-7.4) to 3.0 (CI 0.2-5.8), which is also reflected by a decline in the 10-year cumulative incidence for all cancers from 10% to 5%. However, the relative risk of late cardiovascular death, which is closely related to previous irradiation, barely changed, as shown by a decrease from 2.4 (CI 0.4-4.5) to 2.2 (CI.0-4.7). HD survivors profited less from the sharp decline in cardiovascular mortality observed for the general population. Among patients, the prevalence of serious treatment-related morbidity 5 years or more after initial diagnosis was 34%. In conclusion, modest decline in excess mortality among cured HD patients was observed in the 1980s, as reflected by a decrease in mortality due to second malignancies. However, late mortality, especially due to radiation-related cardiovascular disease, is still substantial. About one third of HD survivors suffer radiation-induced sequelae. Clinical trials to find ways to minimize iatrogenic complications are important.

Risk factors for reduced pulmonary function after malignant lymphoma in childhood.

The aim was to study pulmonary function after Hodgkin disease or non-Hodgkin Lymphoma in childhood and to evaluate if younger age at diagnosis and therapy is a risk factor for reduced pulmonary function. We studied a population-based sample of survivors of Hodgkin disease (n = 22) or non-Hodgkin lymphoma (n = 19) in childhood. Pulmonary function test results were compared with reference values for our laboratory, generated by adjusting published reference values fit 348 healthy never-smokers from a local population study. Data were analyses as standardised residuals, which are [observed minus predicted value] divided by the residual standard deviation of the reference equations. At a median of 11 years after diagnosis (range 2 to 24), the participants had significantly reduced lung volumes and transfer factor, unrelated to the few pulmonary symptoms. On average, the total lung capacity was reduced to -0.9 standardised residual and the transfer factor was reduced to -1.3 standardised residual. Young age at therapy seemed to be a risk factor for reduced lung function, especially when treatment included thoracic irradiation. No significant toxic synergism was observed between smoking and previous cancer therapy. Therapy without thoracic irradiation but with doxorubicin and cyclophosphamide was almost as toxic to lung function as therapy with thoracic irradiation but without doxorubicin and cyclophosphamide. In conclusion, lung volumes and transfer factor were reduced several years after childhood Hodgkin disease of non-Hodgkin lymphoma, with young age at therapy as a risk factor, especially when combined with thoracic irradiation.

Comparison of psychosocial adaptation of advanced stage Hodgkin’s disease and acute leukemia survivors

The purpose of this study was to compare the long-term psychosocial adaptation of Hodgkin's disease and adult acute leukemia survivors. Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute leukemia (AL) survivors were interviewed by telephone concerning their psychosocial adjustment and problems they attributed to having been treated for cancer, using identical research procedures and a common set of instruments. The following measures were used: Psychosocial Adjustment to Illness Scale (PAIS); Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index (NSI). All participants had been treated on one of nine Hodgkin's disease or 13 acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966-1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL = 5.6). HD survivors' risk of having a high distress score on the BSI was almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs. 14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations above the norm, suggestive of a possible psychiatric disorder. HD survivors reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001), greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning (PAIS Sexual Relationships, P = 0.0001), than AL survivors. Treatment-related issues may have placed HD survivors at a greater risk for problems in long-term adaptation than AL survivors.

Second cancers following pediatric Hodgkin's disease.

To define the magnitude of second cancer risk among pediatric Hodgkin's disease survivors and to determine which factors influence this risk. At Stanford,694 children and teenagers were monitored for 1 to 31.6 years (mean, 13.1) after treatment for Hodgkin's disease. Relative risks (RRs), actuarial risks, and absolute excess risks for second malignancies were calculated. The influences of sex, age, stage, splenectomy, treatment and relapse were assessed by multivariate analysis. Fifty-six patients developed 59 secondary malignancies: 48 solid tumors, eight leukemias, and three non-Hodgkin's lymphomas. The RR of developing a second cancer was 15.4 (95% confidence interval [CI], 10.6 to 21.5) for females and 10.6 (95% CI, 6.6 to 16.0) for males. Breast cancer (n = 16) and sarcoma (n = 13) were the most common solid tumors. The actuarial risk at 20 years follow-up evaluation was 9.7% for males, 16.8% for females, and 9.2% for breast cancer. The median interval to diagnosis of a second malignancy was shortest for leukemia, 4.3 years, and longest for lung cancer, 18.4 years. Relapse of Hodgkin's disease increased the risk of second malignancy (hazards ratio [HR] = 2.6, P < .001). Hodgkin's disease stage, patient age, splenectomy, and treatment modality did not appear to alter overall risk, although chemotherapy was associated with subsequent leukemia. Aggressive Hodgkin's disease therapy is successful, but patients have a significant risk of second malignancy. Newer treatment programs focus on obtaining a relapse-free cure of Hodgkin's disease with judicious use of radiation and alkylating agent chemotherapy. Survivors of pediatric Hodgkin's disease require lifelong evaluation and cancer screening.

Chromosome Breaks and Sister Chromatid Exchange as Predictors of Second Cancers in Hodgkin's Disease

Hodgkin's disease (HD) survivors face an increased risk of developing second cancers. We evaluated baseline cytogenetic biomarkers, sister chromatid exchange (SCE) and chromosome breaks [spontaneous (SCB) and bleomycin-induced (BIB)], as predictors of second cancer risk in a cohort of 105 adult HD patients. During follow-up, seven second cancers occurred. SCBs and BIBs showed no association with risk of second primaries. Multivariate Cox regression revealed that high levels of SCEs (relative risk (RR) = 11.3, p = 0.02) and age (RR = 1.08, p = 0.02) predicted second cancer risk. Histology, stage, and treatment were not associated with elevated risk. In conclusion, baseline SCE frequencies may be a useful biomarker for identifying HD patients at increased risk of developing second cancers. These results need to be verified in a larger cohort with a longer follow-up time.