Adjuvant Radiotherapy to Initial Bulky Disease in Patients with Advanced Stage Hodgkin's Disease

To determine if the use of adjuvant radiotherapy to sites of initial bulky disease and adequate modern chemotherapy in patients with advanced stages (IIIB and IV) Hodgkin's disease could improve duration of remission and overall survival.

Patients previously untreated with pathologically documented advanced stages Hodgkin's disease were randomly assigned to received chemotherapy alone with EBVD regimen (epirubicin, bleomycin, vinblastine and dacarbazine): 56 patients or combined therapy: The same chemotherapy regimen following by adjuvant radiotherapy (35 Gy) to sites of initial bulky disease (tumor mass >7 cm diamenter): 54 patients.

Five year overall survival rates were 88% (48 patients) and 60% (34 patients) from combined therapy compared to chemotherapy alone respectively (p < 01) (95% confidence interval (CI): for the difference 18% to 39%). Five-year failure free survival were 83% and 50% respectively (p < 01) (95% CI for difference: 22% to 35%). Toxicity was moderate and well tolerate. No death-related treatment were observed. After a median follow-up of 66 months, no second solid neoplasmas or acute leukemia has been observed.

The use of adjuvant radiotherapy to sites of initial bulky disease following the use of modern chemotherapy in patients with advanced stages Hodgkin's disease improve outcome with increase in failure free survival and overall survival, with moderate toxicity. More randomized clinical trials are warranted to define this therapeutic approach.     

Hodgkin's Disease in Sarcoidosis: A Case Report and a Review of the Literature

ABSTRACT. A patient with Hodgkin's disease preceded by sarcoidosis is presented and the difficulties introduced by the lack of specificity for the sarcoid-like granulomas to differentiate between the dual pathology are discussed. A review of the literature disclosed 9 similar case reports. It is suggested that the finding of non-caseating epithelioid cell granulomas in relatively old patients with lymphadenopathy, systemic symptoms and absolute neutrophil leucocytosis could be warning signals of the appearance of Hodgkin's disease.     

Is Staging Laparotomy of Therapeutic Value in Patients with Supradiaphragmatic Hodgkin's Disease,Clinical Stage IA-IIA?

Between 1968 and 1972, 123 patients with clinical stage (CS) IA and IIA Hodgkin's disease were seen. Staging laparotomy was introduced in June 1970. The impact of staging laparotomy on the prognosis has been evaluated by comparing the treatment results before and after the introduction of this procedure. The patients were treated only on the basis of CS before staging laparotomy, and mainly on the basis of pathological stage (PS) after the introduction of this procedure. Patients with stage IA to IIIA disease received radiotherapy alone with the extended field techniques, while patients with stage IVA disease had combination chemotherapy. After an observation time of 7 years there was no difference in survival between the two groups. The relapses occurred earlier in the patients treated after the introduction of staging laparotomy. It is shown that the survival is unaffected by staging laparotomy in the patients with Hodgkin's disease CS IA and IIA.     

Prognostic Factors in Hodgkin's Disease

An unselected material of 83 consecutive and previously untreated adult patients with Hodgkin's disease (HD) from the Stockholm area is presented. The distribution of patients according to age was characteristically bimodal. The histopathological subtypes were 16 % lymphocyte predominance (LP), 33 % nodular sclerosis (NS), 37 % mixed cellularity (MC) and 11 % lymphocyte depletion (LD). The patients were treated with aggressive megavoltage irradiation and multidrug chemotherapy. Major factors affecting prognosis were age, clinical stage and constitutional symptoms. Patients with LP and NS subtypes had only slightly better prognosis than patients classified as MC and LD. The overall survival was 68 % at 4½ years, which is close to that reported from other groups with similar composition of their materials with regard to age, histopathology and stage.     

Surgical restaging of advanced Hodgkin's disease after first line chemotherapy.

47 patients with stages IIIB and IV Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first-line chemotherapy (CT) which included 4 cycles of CT ABV/IMEP/PCAV/ABV. After surgical restaging (SR), all patients were scheduled to receive 2 additional cycles IMEP/PCAV followed by TNI 20 Gy and patients with residual clinical abnormality or positive restaging surgery received a 20 Gy boost to these areas. 11 patients (23.4%) were found to have active disease in the spleen (10 patients) and/or the lymph nodes (3 patients) after SR. In the spleen, foci of active disease had a size in millimeters and confirm the limits of clinical restaging. According to the response to CT, 5 of the 35 patients (14%) clinically restaged as good responders had active disease; 6 of the 12 patients (50%) clinically restaged as poor responders had active disease. SR is of interest in selected patients with slowly responding disease to determine the indication of an extended field RT for responding patients and salvage therapy for patients resistant to CT.     

Prognostic Influence of Early Diagnostic Splenectomy in Hodgkin's Disease

ABSTRACT. The influence of early laparotomy with splenectomy on prognosis in patients with Hodgkin's disease who were regarded as having uncertain prognostic indices (all patients except those with lymphocytic predominance and nodular sclerosis stages IA and IIA with right-sided presentation, stage IV disease, splenomegaly or age >65 years) was evaluated in a randomized trial initiated in Jan. 1973. The patients were treated with total nodal irradiation (excluding the splenic and hepatic areas) and 33 of 69 patients were randomized to laparotomy with splenectomy. No significant difference in relapse-free or overall survival was found between the two groups after a median observation time of 85 months. Progressive or recurrent disease was as common in splenectomized as in non-splenectomized patients. Splenectomized patients with splenic tumour involvement fared worse than those without. It is concluded that diagnostic laparotomy with splenectomy is of no benefit in this clinical setting.     

Pel-Ebstein Fever Coinciding with Cyclical Haemolytic Anaemia and Splenomegaly in a Patient with Hodgkin's Disease

A 46-year-old man with an aortic valve replacement was investigated for recurrent episodes of fever associated with splenomegaly and haemolytic anaemia. Initially bacterial endocarditis was suspected. At laparotomy he proved to have mixed cellularity Hadgkin's disease confined to the spleen. The undefined mechanism underlying Pel-Ebstein fever in this patient may also have been the cause of simultaneous haemolysis and splenomegaly.     

Lymphocyte ATP-ase Activity in Treated Cases of Hodgkin's Disease

The ATP-ase activity was determined in lymphocytes isolated from peripheral blood in 41 patients with Hodgkin's disease and 50 healthy controls. All patients were previously treated with irradiation or cytostatic drugs and 17 patients were under maintenance therapy at the time of investigation. A significantly increased ATP-ase activity was found in lymphocytes from patients with Hodgkin's disease. The individual activities were unrelated to the clinical stage of the disease, but correlated to the histological classification of the lymphatic tissue. Significantly lower lymphocyte ATP-ase activity was found in patients under maintenance treatment with immunosuppressive drugs, especially if the patients had previously been irradiated. It is suggested that the ATP-ase activity of circulating lymphocytes is related to the immunological activity against the presence of the malignant cells in Hodgkin's disease.     

Outcome of secondary myeloid malignancy in Hodgkin's disease: the BNLI experience

Abstract: In Hodgkin's disease where the majority of patients are long-term survivors secondary myeloid malignancies are a well-documented complication. The survival of those who develop secondary myelodysplasia/ acute myeloid leukaemia (MDS/AML) is historically said to be extremely poor. This study from the BNLI database of over 4900 patients with Hodgkin's disease reports long-term follow-up of 30 patients with secondary MDS/AML. Five patients have survived at least 5 yr (1>12 yr) from the time of diagnosis of AML. These patients were significantly younger (p=0.03) than those who succumbed to this complication and each also had standard or favourable risk cytogenetics. The actuarial 5- and 10-yr survival rates are 17.4% (7.7–34.9%, 95% CI) and 8.7% (1.9–31.7%, 95% CI), respectively. There is therefore a subgroup of patients who will achieve long-term survival despite the development of secondary myeloid malignancy.     

Prognostic factors in Hodgkin's disease stage III with special reference to tumour burden

143 patients with Hodgkin's disease stage III (65 PS III, 78 CS III) were treated with radiotherapy alone (33 patients), combination chemotherapy alone (56 patients), or radiotherapy plus combination chemotherapy (54 patients). They were followed till death or from 7 to 191 months. Prognostic factors including treatment, peripheral + intrathoracic tumour burden (assessed by combining tumour size in each involved region with number of involved regions), intraabdominal tumour burden (assessed by combining size of lymphographically involved lymph nodes in each region with number of lymphographically involved regions), histologic subtype, B-symptoms, number of involved regions, mediastinal involvement, pretreatment ESR, sex, age, laparotomy, and substage were examined in multivariate analysis. With regard to disease-free survival, total tumour burden (intraabdominal and peripheral + intrathoracic) emerged as the only pre-treatment factor of independent prognostic significance. With regard to overall survival the only factor of independent significance apart from age turned out to be intraabdominal tumour burden. The results of the present study thus support recently published findings regarding early stage disease to the effect that tumour burden is the single most important prognostic factor in Hodgkin's disease.     

Chemotherapy-induced myocardial infarction in a young man with Hodgkin's disease.

A 32-year-old male with stage IIIA nodular sclerosing Hodgkin's disease and no cardiac risk factors presented with chest pain after receiving chemotherapy consisting of multiple drugs, including vinca alkaloids. He completed an uncomplicated anterior wall myocardial infarction. Coronary angiography documented the absence of significant coronary artery disease. Exercise stress testing with gated scan confirmed loss of anterior wall motion and a decreased left ventricular ejection fraction. Vascular toxicity, including, rarely, myocardial infarction, has been reported following antineoplastic regimens containing vinca alkaloids. Hypercoagulable states, cardiac invasion by tumor, and coronary artery spasm are possible etiologies. Of these, coronary artery spasm appears most likely. Management should include discontinuation of the offending drug and supportive care.     

Hodgkin's disease, clinical stages IA to IIIB: combined modality therapy (3 MOPP followed by curative and prophylactic radiotherapy including the spleen). Six-year results

From January 1980 to September 1985, 82 patients with IA to IIIB clinical stage (CS) Hodgkin's disease were treated by three MOPP chemotherapy (CT) cycles followed by extended field radiotherapy (RT) including the spleen (30-40 Gy). 2 patients died during the treatment (medullary aplasia, pulmonary edema). 6 were in failure after three MOPP cycles; they received other CT; 3 died and 3 are alive in remission (survival: 2.5 to 3.5 yr). 74 were in complete remission (CR) after completion of treatment. 4 patients relapsed (all alive after re-treatment) and 4 died in first CR (tuberculosis, hepatitis, myeloma, unknown cause). At 6 yr, actuarial survival and relapse-free survival are respectively 89.8% for the 82 patients and 93% for those in CR. These good results are due to: the administration of CT before RT, limited to three cycles; identification of failures after CT; inclusion of the spleen in RT ports in all cases; and a short lumbo-aortic port in CS I and II.     

Critical value of laparotomy with splenectomy in stage III Hodgkin's disease as restaging procedure after chemotherapy

38 patients with stage III Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first line chemotherapy which included MOPP, ABVD, or both. 28 patients were judged to be in clinical complete remission (CR) and 10 were resistant or had relapsed. Among patients in CR, 27 (96%) were confirmed to be in pathological CR; among patients resistant or relapsed, 9 (90%) were confirmed to have disease in the abdomen or retroperitoneum. The therapy for patients in clinical remission before laparotomy consisted of TNI or sTNI in 19 patients, mediastinal radiation in 6 patients and no further therapy in the remaining 3 patients. No significant differences were seen in survival and relapse-free survival between those patients treated by extensive and those treated by local radiotherapy or no further therapy. Instead, among those patients who received extensive radiotherapy 3 developed acute non-lymphoid leukemia (ANLL). The therapy for this group of patients consisted of further chemotherapy in 7 who had concomitant liver involvement and TNI in the remaining 3 who had the disease confined to the spleen and/or lymph nodes. Among these patients, only 3 obtained CR; 2 with radiation and 1 who was resistant to MOPP, with ABVD. This study leads us to re-consider the role of laparotomy in stage III HD which should be used as non-routine procedure only in selected patients without poor prognostic factors who may be cured by radiotherapy alone. In patients resistant to chemotherapy, an early evaluation of disease in the abdomen may be useful for a better salvage treatment.     

Elevated Plasma Lysozyme in Hodgkin's Disease An Indicator of Increased Macrophage Activity?

Plasma lysozyme levels were studied in 42 patients with Hodgkin's disease and were found significantly increased. Plasma lysozyme varied with the stage of the disease and with symptoms, but did not correlate with the histological subtype or with blood neutrophil and monocyte counts. Serial measurements in four patients on MOPP treatment showed a rapid decrease following treatment. The increased plasma lysozyme in Hodgkin's disease stems most likely from the macrophage system, either because the macrophages are hyperactive and/or because the malignant cell in Hodgkin's disease is of macrophage origin.     

Prognostic Significance of Large Mediastinal Involvement in Hodgkin's Disease

Relapse rates of 75 patients with previously untreated Hodgkin's disease with stages I and II nodular sclerosis were analyzed according to the mediastinal involvement. The overall relapse rate was 22.6%. The probability of relapse was much greater for patients with large mediastinal involvement (66.6%) compared with 17% for patients with small mass, and 11.7% of patients without mediastinal involvement (P < 0.001). There was no significant difference in recurrence rates between patients without mediastinal mass and patients with a small mass, and in these patients adjuvant chemotherapy MOPP after radiotherapy showed an evident benefit in reducing the relapse rate. On the other hand, no benefical effect of adjuvant chemotherapy was observed in patients with large mediastinal involvement. Finally, in the 17 relapsing patients, ‘salvage’ chemotherapy was less effective in patients with large mediastinal mass than in those with small or no mediastinal involvement.     

Chromosome Abnormalities Identified by Banding Technique in a Patient with Acute Myeloid Leukaemia Complicating Hodgkin's Disease

Chromosome analyses using the Giemsa banding technique were performed on bone marrow cells in a patient with the association of Hodgkin's disease and acute myeloid leukaemia. All cells had an abnormal karyotype showing an extra chromosome No. 14, loss of one chromosome No. 17 and gain of one chromosome No. 18. These abnormalities are in many respects similar to the karyotype changes of lymphoid cells in malignant lymphomas, suggesting a pathogenetic relationship between the two disorders.     

The Incidence and Characteristics of Acute Myeloid Leukaemia Arising in Hodgkin's Disease

In 201 consecutive patients with Hodgkin's disease treated from 1964 through 1975 with intensive irradiation and/or combination chemotherapy 3 cases of acute myeloid leukaemia were observed. The observed number of cases was 75 times over the expected (P < 0.01). An analysis of 47 reported cases of acute myeloid leukaemia arising in Hodgkin's disease shows that these cases differ considerably from ‘spontaneous’ cases of acute myeloid leukaemia by appearing in a much younger age group, by a very poor response to anti-leukaemic chemotherapy, and by a relatively low male/female ratio (0.84). The intensification of radiotherapy and cytostatic therapy of Hodgkin's disease during the last decade is considered the explanation of the increased incidence of acute myeloid leukaemia in these patients.     

Vanishing Bile Duct Syndrome in a Hodgkin's Lymphoma Patient with Fatal Outcome Despite Lymphoma Remission

Vanishing bile duct syndrome (VBDS) is a condition resulting from severe bile duct injury, progressive destruction, and disappearance of intrahepatic bile ducts (ductopenia) leading to cholestasis, biliary cirrhosis, and liver failure. VBDS can be associated with a variety of disorders, including Hodgkin''s lymphoma (HL). We describe a 33-year-old male patient who presented with lymphadenopathy and jaundice, and was diagnosed to have HL. Serum bilirubin worsened progressively despite chemotherapy, with a cholestatic pattern of liver enzymes. Diagnosis of VBDS was established on liver biopsy. Although remission from HL was achieved, the patient died of liver failure. Presence of jaundice in HL patients should raise the possibility of VBDS. This report discusses the difficulties of delivering chemotherapy in patients with liver dysfunction. HL-associated VBDS carries a high mortality but lymphoma remission can be achieved in some patients. Therefore, liver transplantation should be considered early in these patients.