Solitary cerebral metastasis from a papillary carcinoma of the thyroid.

A woman aged 52 was treated with radioactive iodine for a papillary carcinoma of the thyroid. Four years later she developed signs and symptoms of an intracranial space occupying lesion. A computed tomographic scan showed a mass in the right posterior frontal region. Although she was suspected of having metastatic disease a definite diagnosis was not established until she died 6 months later when post-mortem examination confirmed that she had a cerebral metastasis from a papillary carcinoma of the thyroid. There was no evidence of metastatic disease elsewhere in the body. Cerebral metastases from papillary carcinoma of the thyroid are uncommon but may occur in patients who have metastases in bones or lungs. A search of the literature has revealed only two patients with solitary cerebral metastases.

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia.

Between August 1985 and October 1987 we treated 35 patients with chronic myeloid leukaemia (CML) by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n = 31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n = 35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. The addition of TLI to the standard protocol did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. We conclude that the addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This benefit is not associated with significantly increased toxicity.

The use of radioactive iodine in thyroid carcinoma.

The use of radioactive iodine (131I) for the treatment of primary carcinoma of the thyroid and as an alternative to a surgical thyroidectomy in the management of patients with metastatic disease is described. The rationale for using 131I to ablate normal thyroid tissue after a surgical thyroidectomy is considered in relation to the natural history of papillary and follicular tumours and in recognition of the results of such a policy in some recently reported series. It is concluded that 131I ablation is indicated in patients with follicular tumours: and in patients with papillary tumours if they are over the age of 40 or if the tumour contains a substantial follicular component. The management of patients undergoing post-operative 131I ablation is outlined and the possible complications of such treatment which include radiation thyroiditis, radiation sialitis, transient hyperthyroidism and oedema of the neck are described.

Oedema of the neck after ablation of the thyroid with radioactive iodine.

Six out of 30 patients who underwent thyroid ablation with 131I during the period 1975-85 developed acute oedema of the neck within 48 h of the therapeutic dose. The condition was painless and responded well to treatment with corticosteroids. The early onset and absence of pain distinguish this complication from radiation thyroiditis. Dosage calculations and thermoluminescent-dosimeter measurements of the dose at various points on the anterior surface of the neck of a patient with a toxic adenoma of the thyroid treated with 131I were in fairly good agreement with one another and confirmed that the oedema of the neck could not be a direct effect of irradiation on the extrathyroidal tissues. It is suggested that this phenomenon may be a hypersensitivity reaction associated with massive destruction of thyroid tissue.

Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse.

Between December 1983 and November 1985 we treated 39 patients with chronic myeloid leukaemia by chemoradiotherapy and transplantation from HLA-identical sibling donors using bone marrow that had been depleted of T cells ex vivo with the rat monoclonal antibody Campath-1. Twenty-eight of the patients were in the chronic phase (good-risk group) and 11 patients were in more advanced phases of the disease (accelerated phase or blastic transformation; poor-risk group). Of the patients of good risk 23 (82%) survive; the median duration of follow-up is 461 (range 111-776) days; of the 11 patients of poor risk four survive; the median duration of follow-up is 280 (range 189-658) days. Acute graft-versus-host disease (GVHD) of grade II or greater occurred in three (11%) of the patients of good risk and in six (55%) of the patients of poor risk. In the patients of good risk haematological evidence of relapse was seen in four and cytogenetic evidence of persisting or relapsed leukaemia (based on the finding of Philadelphia-chromosome-positive marrow metaphases more than 6 months after transplant) was seen in three other patients. In comparison with the patients of good risk transplanted with untreated marrow between February 1981 and December 1983, the incidence of acute GVHD was reduced significantly (P less than 0.001) but the risk of leukaemic relapse (including patients with only cytogenetic evidence of relapse) was increased (P less than 0.005). We conclude that T-cell depletion used in this manner may be associated with an increased risk of leukaemic relapse.

Long-term results from graded low dose radioactive iodine therapy for thyrotoxicosis.

An analysis has been made of the results of treatment in a series of 261 consecutive patients given graded low dose radioactive iodine therapy for thyrotoxicosis. Of these patients, 140 (54%) became euthyroid after a single dose of 131I and a further 50 (19%) achieved a remission after supplementary treatment with an antithyroid drug; 45 patients (17%) required further treatment with 131I which was invariably curative. The incidence of hypothyroidism was 10% at 1 year. The subsequent incidence of hypothyroidism in the whole group was 27% at 5 years, 40% at 10 years and 53% at 15 years. Patients continued to become hypothyroid at a constant rate of 3% per year. The incidence of early hypothyroidism can be reduced to some extent by using low doses of 131I and by relating the dose to the size of the gland. Late hypothyroidism on the other hand is due to latent nuclear damage and is inherent in the method of treatment.

Bone marrow transplantation for patients with chronic myeloid leukemia.

Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72 percent, and the actuarial risk of relapse was 7 percent. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18 percent, and the actuarial risk of relapse was 42 percent. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established.

Spinal extradural angiosarcoma occurring after treatment for Hodgkin's disease.

An extradural angiosarcoma was found invading the L3 and L4 nerve roots. An angiosarcoma has not previously been reported in this situation. The tumour was diagnosed eighteen years after the patient presented with Hodgkin's disease and was possibly induced by the treatment given for this disease.

Fractionation of whole body irradiation before bone marrow transplantation for patients with leukaemia.

Thirty patients in various stages of acute leukaemia or chronic granulocytic leukaemia (CGL) were treated with cytotoxic drugs followed by whole body irradiation (TBI) administered in 200 cGy fractions twice daily to a total of 1000 or 1200 cGy. The immediate toxicity of fractionated TBI administered in this way was negligible and patients required only minor premedication and little treatment subsequently for complications attributable to TBI. Fourteen (47%) patients have died, ten of the 12 transplanted with active disease, and four of the 18 subjected to transplantation in remission of acute leukaemia or in chronic phase of CGL. Though the duration of follow-up is still short, no patient in the latter group (follow-up of survivors ranging from six to 146 weeks) has yet relapsed with any evidence of recurrent leukaemia. We conclude that this method of fractionating TBI reduced toxicity for the patient without necessarily reducing its antileukaemic effect.

Marrow transplantation for patients in the chronic phase of chronic granulocytic leukaemia.

In 1979 two patients with Philadelphia (Ph1)-chromosome-positive chronic granulocytic leukaemia (CGL) were treated with chemoradiotherapy and transplantation of bone marrow from their respective identical twins. Subsequently twelve patients with Ph1-positive CGL in chronic phase were treated with chemoradiotherapy followed by transplantation of bone marrow from their HLA-identical sibs. Two of the fourteen patients have died of complications of the transplant procedure; twelve patients are alive and well. All the survivors have normal or nearly normal blood counts; there is no evidence of recurrent leukaemia or Ph1-positive cells in any patient after follow-up periods ranging from 97 to 1112 days. Bone-marrow transplantation should be considered in the management of any young patient with CGL who has a suitable marrow donor.

Carbon monoxide diffusing capacity in polycythaemia rubra vera.

The diffusing capacity of the lung, or transfer factor, for carbon monoxide (TLCO) was measured in 12 patients with polycythaemia rubra vera. This was significantly raised (mean 152% predicted, SEM +/- 14%) and remained so even after correction to a standard haemoglobin concentration of 14 . 6 g/dl (mean 139% predicted, SEM +/- 13%). Serial measurements of TLCO on two patients after treatment of polycythaemia rubra vera showed a greater fall in relation to haemoglobin concentration than would have been predicted on theoretical grounds if the increases in TLCO had been due entirely to the increased haemoglobin concentration. The pulmonary capillary blood volume (estimated from TLCO) also fell in these two patients after treatment. There was a strong correlation between TLCO and the technetium-99m-labelled red cell volume for the seven men (r = 0 . 92; p less than 0 . 01) and five women (r = 0 . 99; p less than 0 . 001) when studies were performed on the same day. In patients with polycythaemia rubra vera who have no evidence of coexistent pulmonary disease the pulmonary capillary bed appears to share in the expansion of the body blood volume. The single-breath TLCO test may act as a convenient and simple monitor for the response of the disease to treatment.

Adult T-cell lymphoma-leukaemia in Blacks from the West Indies.

Six Black patients (five born in the West Indies and one in Guyana), aged 21-55 years, had adult T-cell lymphoma-leukaemia diagnosed in the U.K. This disorder is rare in Europe and the U.S.A., but is more common in Japan. Five patients had severe hypercalcaemia which correlated with disease activity, although osteolytic lesions were found in only one. Other clinical features were lymphadenopathy and a high white blood-cell count (range 27-67 X 10(9)/l) with a predominance of pleomorphic lymphoid cells with pronounced nuclear irregularities prominent at ultrastructural level. The cells in all cases formed rosettes with sheep red blood-cells and lacked terminal transferase. Analysis with OKT monoclonal antibodies in four cases confirmed a mature T-cell phenotype defined as helper/inducer (T4+, T6-, T8-) in three. Combination chemotherapy resulted in short-lived remissions; four patients died and two have survived 3-6 months. The disease in these patients is indistinguishable on clinical and pathological grounds from adult T-cell leukaemia/lymphoma in Japan. Geographical clustering among certain racial groups suggests common aetiological factors in the pathogenesis of this disease. The finding of high titre antibody against the structural core protein (p24) of a new human C-type leukaemia virus (human T-cell leukaemia/lymphoma virus) in all tested cases from this series and data from all but one case from Japan suggest that one such factor may be viral.

Splenic irradiation in B-prolymphocytic leukaemia.

Twelve patients with B-cell prolymphocytic leukaemia (PLL) were treated with splenic irradiation at a weekly dose of 100 cGy to a maximum total dose of 1000 cGy. There was no morbidity associated with this treatment. SEven patients responded. Three achieved a good response and four a partial response. Two of the patients who had a partial response have subsequently died of unrelated causes. Four of the five patients who failed to respond have died as a result of their disease. When more than 25% of the prolymphocytes formed rosettes with mouse red blood cells (MRBC) the patients appeared to respond better to splenic irradiation. There was no correlation between response and the initial white cell count or the size of the spleen.