Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation.

OBJECTIVE--To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation''s studies of Hodgkin''s disease since 1970. PATIENTS--2676 Patients entered into Hodgkin''s disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. DESIGN--Retrospective analysis of multicentre trial data by case-control and life table methods. RESULTS--17 Cases of secondary leukaemia were recorded in this group of 2676 patients, giving an overall risk at 15 years of 1.7%. The risks of leukaemia after chemotherapy alone and chemotherapy with radiotherapy were not significantly different. The risk of leukaemia increased sharply with the amount of treatment given as measured by the number of attempts at treatment. The 15 year risks of leukaemia were 0.2%, 2.3%, and 8.1% for patients receiving one, two, or three or more attempts at treatment. The highest risk, 22.8% at 15 years, was observed in patients treated with lomustine (CCNU), and a case-control study suggested that this was an independent risk factor. The risk of secondary leukaemia was largely related to the overall quantity of treatment, although exposure to lomustine seemed to be an important risk factor. Treatment with both drugs and radiation was not more leukaemogenic than treatment with drugs alone. The greatest risk of secondary leukaemia was seen in multiply treated patients who were unlikely to be cured of Hodgkin''s disease. CONCLUSIONS--Avoidance of secondary leukaemia should be a minor factor in the choice of treatment for Hodgkin''s disease.     

Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin''s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin''s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin''s disease and of second primary non-Hodgkin''s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin''s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin''s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin''s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin''s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin''s disease.     

Prednisone in MOPP chemotherapy for Hodgkin's disease.

High remission rates have been produced by MOPP (mustine, vincristine, procarbazine, and prednisone) chemotherapy in patients with advanced Hodgkin''s disease, but the prednisone component has caused adverse effects in patients who have undergone radiotherapy. The remission rates and length of remission were reviewed in 211 patients with Hodgkin''s disease who received chemotherapy either with or without prednisone. In contrast to the findings of a British study, there were no significant differences in remission rates or length of remission between patients who had received prednisone and patients who had not. There were differences between the British prospective study and this retrospective one, but it is difficult to know what accounted for the substantial differences in the findings.     

A modified MOPP regimen in the treatment of Hodgkin's disease stage III B and IV (author's transl)

In a retrospective study 80 patients with Hodgkin's disease of stage III B (n = 32) and IV (n = 48) were investigated, who had been treated with a modified MOPP regimen. 28 patients (35%) were previously untreated. A completed remission was reached in 51 patients, a partial remission in 16, and 13 patients failed to respond. 16 patients had died in the observation period. Complete remissions were twice as frequent with 90% in stage III as compared with 45% in stage IV. The group of patients surviving 4 years was 92% in stage III and 62% in stage IV.     

Radiotherapy in the treatment of Hodgkin's disease.

Eighty-seven untreated patients with localised Hodgkin''s disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin''s disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.     

Intensive investigation in management of Hodgkin's disease.

Ninety-eight patients with clinically localised Hodgkin''s disease underwent laparotomy and splenectomy to determine the extent of microscopic spread. In 68 patients the procedure was carried out for untreated disease apparently confined above the diaphragm. Abdominal disease cannot be confidently excluded on the basis of non-invasive investigation at presentation. Clinical assessment of splenic disease was unreliable unless gross splenomegaly was present. Pedal lymphography was accurate in assessing para-aortic and iliac disease but of no value in assessing other intra-abdominal lymph node involvement, including that of the mesenteric lymph node. Trephine bone marrow biopsy findings were normal in all patients before surgery, and only one patient was found to have diseased bone marrow by Stryker-saw biopsy at operation. Liver disease was identified at operation in nine patients, some of whom were asymptomatic with clinically undetectable splenic and nodal disease. Detailed clinical staging failed to detect disease in one-third of patients who underwent laparotomy. These studies show that if radiotherapy is to remain the treatment of choice for disease truly localised to lymph nodes a detailed staging procedure, including laparotomy and splenectomy, remains essential. The value of this potentially curative treatment is considerably diminished in the patient who has been inadequately staged.