Progressive disease after ABMT for Hodgkin's disease

A major limitation of ABMT for relapsed/refractory Hodgkin's disease is disease recurrence post-transplantation. We retrospectively reviewed 68 patients undergoing ABMT from January 1987 to June 1993. All received a uniform preparatory regimen (CBV). The median patient age was 30; 75% received prior radiation therapy and all patients received prior chemotherapy. Thirty-one percent presented at the time of transplantation with tumor masses larger than 10 cm. Sixty-two percent received autologous marrow alone and 38% PBPC with or without autologous bone marrow. Overall and progression-free survival are 43 and 36% at 5 years. Median follow-up for survivors is 59 months. Multivariate analysis revealed that tumor bulk was the most powerful poor prognostic factor for both survival and progression-free survival. Those transplanted with non-bulky tumors had an overall survival and progression-free survival of 52 and 44%, respectively, compared to those transplanted with bulky tumors who had an overall survival and progression-free survival of 22 and 16% (P = 0.03 and P = 0.04, respectively). Twenty-seven patients have relapsed. Four relapsed more than 2 years after ABMT. Four of the 27 patients who have relapsed remain alive, two without evidence of disease. The time after transplant to relapse was prognostically important, with no patients who relapsed within 6 months of ABMT still being alive, compared with 25% of patients who relapsed 7 or more months after ABMT who are still alive. We conclude that salvage therapy for relapse after ABMT is appropriate, as some patients may achieve prolonged survival. The time from transplant to relapse is an important survival predictor.     

Increased mortality after successful treatment for Hodgkin's disease

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.     

Curative potential of combined modality therapy for advanced Hodgkin's disease

During the period from 1969 through 1977, 124 patients with advanced Hodgkin's disease underwent treatment with combination chemotherapy and radiotherapy. Sixty-three cases were previously untreated, and 61 were relapses following radical radiotherapy for localized Hodgkin's disease. No patient in this series had received prior chemotherapy. Of 102 patients (84%) who have entered complete remission, 92 remain in complete remission with a median follow up time of five years, 10 patients having relapsed, and acute leukemia having developed in 2. The cumulative survival rate for all 124 patients is 80% at five years; the relapse-free survival rate is 74%. In many, if not most cases, the Hodgkin's disease appears to be cured. We have also identified two subgroups of patients for whom the prognosis is worse than for patients with advanced-stage disease as a whole. Patients over the age of 40 years have a five-year survival rate of only 45%, compared with 89% for all other patients. Those Stage IV patients with multiple extranodal sites of involvement have a five-year survival rate of 48%, compared with 81% for other Stage IV patients with only a single extranodal site involved.     

Precocious myocardial infarction after radiation treatment for Hodgkin's disease

A 26-year-old man received extensive cardiac radiation in the course of treatment of mediastinal Hodgkin's disease, and six years later, he experienced an acute myocardial infarction. Angiographic studies demonstrated extensive atherosclerotic abnormalities in the coronary arterial system. It is suggested that radiation-induced injury was a provocation of these precocious arterial abnormalities.     

Long term remissions with combined modality therapy for advanced Hodgkin's disease

A new treatment program for advanced Hodgkin's disease employing five-drug combination chemotherapy and low dose radiation to the sites of bulk disease (nodal or parenchymal) was designed in 1969. Eighty patients have now been treated, 60 of whom have achieved a complete remission. More significantly, only 5 of the 60 completed responders have relapsed with follow-up from 1-6 years. The cumulative survival at 5 years of patients entering complete remission is 92%. For those patients not sustaining a complete remission, it is 19% at 2 years. This program has resulted in substantially lower relapse rates than previously reported by other investigators, probably because of the administration of radiotherapy in the manner described. Hopefully, a significant number of these patients may be cured of their disease.     

Calcifications in mediastinal lymphoma after radiation therapy of Hodgkin's disease. (author's transl)

One case of calcifications in mediastihal lymphoma after radiation therapy of Hodgkin's disease is reported. The incidence of these calcifications is remarkably low. They are mostly localized in the anterior mediastinum showing a characteristical pattern which is initially stippled, later confluent and coral-shaped. An open interval after radiation therapy is typical for this phenomenon. The cause of the calcifications is discussed.     

Functional imaging of Hodgkin's disease with FDG-PET and gallium-67

We report a case of Hodgkin's lymphoma (Stage I B) which was studied using Ga-67-scintigraphy as well as whole body FDG-PET. Ga-67-scintigraphy detected a slightly increased uptake in the paraaortic and pelvic lymph nodes. However, FDG-PET was able to localize a much larger number of affected foci with a high glucose utilization rate in the right and left paraaortal regions, in the middle of the epigastrium, in the right and left parailiacal regions and one focus in the left upper mediastinum. Our experiences give rise to the assumption that FDG-PET ist significantly superior to gallium scintigraphy in Hodgkin's disease. Whole body FDG-PET can result in an upstaging of the patient and has therefore a major impact on the therapeutic management.     

Evans syndrome after autologous bone marrow transplant for recurrent Hodgkin's disease

The association of immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) with Hodgkin's disease has been known for many years. Autoimmune cytopenia has also been described in patients that have undergone allogeneic or autologous bone marrow transplantation. We report a rare case of Evans syndrome in a patient 3 years after autologous bone marrow transplantation for recurrent Hodgkin's disease.     

Maintenance therapy with interferon alfa 2b in Hodgkin's disease

We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease.     

Male gonadal function in Hodgkin's disease before and after treatment

Twenty eight histologically confirmed cases of Hodgkin's disease were evaluates with regard to libido, sperm count, FSH, LH and urinary ketosteroid levels, before and during different stages of chemotherapy along with testicular biopsy on 16 cases. Decrease in libido during therapy improved following treatment, 50% cases who were oligospermic before treatment became azospermic, Serum FSH levels increased significantly (p 0.001) during the course of treatment. There was no significant change in LH and urinary ketosteroid levels (p 0.05). Testicular biopsy, normal initially, showed germ cell aplasia and absence of spermatogenesis after therapy. Drug induced testicular change leads to sterility.     

Thyroid carcinoma after high-dose external radiotherapy for Hodgkin's disease: report of three cases

Three patients (two female and one male), who had received mantle irradiation for Hodgkin's disease eight, ten, and twelve years previously, developed papillary thyroid carcinoma. The radiation doses to the necks overlying the site of thyroid cancers were 3000, 4000, and 4100 rads, respectively. It has been stated that there is no risk of developing thyroid cancer with such high doses of external irradiation but apparently this complication will be encountered in a small number of patients.     

Cytogenetics of Hodgkin's disease

Cytogenetic studies over the past 35 years have made a major contribution towards the understanding of the nature of Hodgkin's disease by demonstrating unequivocally the consistent presence of a clonal population of cells that have the cardinal features of malignancy e.g. more or less gross aneuploidy, frequently with complex chromosomal changes and showing considerable variation from case to case, thus comparable to the findings in carcinomas and other solid cancers. The mode is frequently in the triploid-tetraploid region, as we found in 17 of 27 cases studied in this laboratory by Feulgen microspectrophotometry, compared to only 10 cases with neardiploid modes. It is disappointing that no specific change, such as a translocation that could give a clue to the chromosomal location of a gene or genes involved in the etiology of Hodgkin's disease, has yet been found. Nevertheless it is clear that a number of nonrandom changes, including several that are also common in other malignancies including the non-Hodgkin's lymphomas, are frequently present, e.g., deletions of 1p, 6q, and 7q. Interestingly, deletions of 4q, with loss of 4q25 --> q27, that have also been reported may show some specificity for Hodgkin's disease.     

The risk of non-Hodgkin's lymphoma after Hodgkin's disease, with special reference to splenic treatment

BACKGROUND AND OBJECTIVE: One of the consequences of the enormous improvement in survival rates of patients treated for Hodgkin's disease (HD) is the emergence in the long term of treatment-related complications, particularly secondary cancers. This study was undertaken to observe the occurrence of non-Hodgkin's lymphoma (NHL) in patients treated for HD and to identify the etiological role of various risk factors, especially spleen irradiation, in the pathogenesis of this illness. DESIGN AND METHODS: From 1972 to 1996, the Department of Radiation Oncology and the Hematology Section of "La Sapienza" University of Rome observed and analyzed the occurrence of NHL in 1,391 patients treated for HD. The average follow-up period was 84 months. For a more accurate calculation of the risk of the occurrence of NHL, the patients were first divided into 3 groups according to their initial treatment and also according to the total treatment they had received. Then, in order to establish the possible connection between NHL and splenic treatment the patients were also divided into 3 subgroups according to whether they had undergone splenectomy, splenic irradiation or neither of these. Two different methods of statistical analysis were used: (a) the cumulative risk (confidence interval) was evaluated in relation to treatment (initial and at the time of salvage) and (b) the Cox model was applied to identify the variables which play a role in the appearance of NHL. The cumulative risk of developing NHL was assessed using the Kaplan and Meier method. A multivariate analysis was performed using the Cox Proportional Hazard Model. RESULTS: A total of 20 cases of NHL were observed, appearing between 17 and 206 months after initial treatment. The cumulative risk was 0.8%, 1.8%, 2.6% and 3.5% at 5, 10, 15 and 20 years respectively. According to the multivariate analysis, significant risk factors were splenic irradiation and age (> 40 years). Splenic irradiation (vs no splenectomy/no splenic irradiation) showed a relative risk of 5.69, p = 0.0280, while age over 40 showed a relative risk of 3.05, p = 0.0152. INTERPRETATION AND CONCLUSIONS: From the results of this study, if appears that there is a possibility that splenic irradiation and age over 40 increase the risk of NHL in HD patients. Further studies are needed to investigate in greater depth the role of spleen irradiation in the occurrence of this illness.     

MR imaging findings after transplant surgery for Parkinson disease

There is a strong correlation between gingival inflammation and clinical and sub-clinical ascorbic acid deficiency. This has created a demand for a handy diagnostic test to detect the ascorbic acid deficiency. The aim of this work was to find out the efficacy of one such test, i.e. the modified Lingual Ascorbic Acid Test (LAAT). To find out the significance of ths LAAT, it was compared with plasma ascorbic acid levels and then confirmed statistically. Our findings suggest that with this simple, reliable and inexpensive method, the dental practitioners can conveniently assess the ascorbic acid status of their patients.