Langerhans cell histiocytosis in adults.

Langerhans cell histiocytosis in the adult is rare, but it is important to recognize its occurrence, as it must be differentiated from lymphoma, myeloma, and a variety of skin conditions and endocrinopathies. It has been reported in patients up to the ninth decade of life, and occurs equally in men and women. Local disease has a good prognosis, but associated diseases--particularly malignancy--may be the cause of death in some adults. The optimal treatment is not known. Coordinated investigation of the epidemiology and therapy of this disease is needed.

The use of 99mTc-MIBI scanning in multiple myeloma.

Tc-99m 2 methoxy-isobutyl-isonitrile (99mTc-MIBI), also called Sestamibi, is a safe and effective scanning agent in solid tumours. Its use in imaging lesions in multiple myeloma has been studied in 21 patients with either multiple myeloma (19/21) or monoclonal gammopathy of undetermined significance (MGUS) (2/ 21). 99mTc-MIBI scanning was positive in 14 patients, 13 with active myeloma and one patient with MGUS showing possible transformation to a more accelerated phase. In seven patients 99mTc-MIBI scanning was negative. In four of them, the result was unexpected, as they had the features of active myeloma. All four were either primarily or secondarily resistant to chemotherapy, with high total cumulative doses of doxorubicin. Overexpression of P-glycoprotein associated with multidrug resistance could be a factor, as it has been shown that 99mTc-MIBI is actively eliminated from the cell by P-glycoprotein. With this assumption, sensitivity of the scanning technique in this series is 100%, and the specificity 88%. No toxicity was experienced by any patient. 99mTc-MIBI scanning is a useful adjunct to the investigation of multiple myeloma, and may have potential as an in vivo test for multidrug resistance.

Langerhans cell histiocytosis in the adult.

A study of 47 well-documented patients with Langerhans cell histiocytosis (LCH) showed a slight female preponderance, with onset as late as the ninth decade. The skin was the commonest site of presentation, but pulmonary and bone involvement was frequent. Patients with single-site disease did best. The worst prognosis was seen in the elderly or those with organ dysfunction. A high incidence of associated malignant disease was seen, which could precede, be coincidental with, or occur after a diagnosis of LCH.

Vincristine and oral etoposide in refractory multiple myeloma.

A total of 15 patients with refractory multiple myeloma (MM; 4 primary unresponsive and 11 relapsed and resistant to re-induction/salvage therapy) received i.v. vincristine on day 1 and oral etoposide daily for 4 days, the treatment being repeated at 3-weekly intervals. The patients were re-assessed after three cycles of chemotherapy, and non-responders received no further therapy. There was no complete or partial response. A minimal response was seen in two patients, and two others showed stable disease. None of the responses was sustained, and all patients eventually had progressive disease. It is concluded that combination chemotherapy with vincristine and oral etoposide given by this schedule is unlikely to be of any value in refractory myeloma.

Myeloma during a decade: clinical experience in a single centre.

One hundred and fifty-six patients with multiple myeloma were treated over a period of 12 years at St. Bartholomew's Hospital. The progress of the disease was affected in 96/156 patients (61%). Response was defined as achieving a plateau of M component. A partial or complete response was seen in 68/120 patients treated conventionally (56.5%), and in 28/36 patients treated with high-dose therapy (77.7%). The median survival of the group as a whole was 20 months, with a 2-year survival of just over 40%. In the 36 patients treated with high-dose therapy, median survival was 6 years, and in a small group who have had maintenance Interferon therapy, the median has not yet been reached. In a univariate analysis, age, intensity of therapy, haemoglobin and creatinine levels were significant, but multivariate analysis showed that only age and intensity of therapy were independent predictors for survival. The outlook for relapsed patients who showed progression of disease remains poor, but palliation was best achieved by steroid and Interferon in combination. Patients who achieve complete responses and are maintained on Interferon appear to be doing better both in terms of freedom from symptoms and in survival, and methods to enable an elderly population to tolerate this form of therapy need to be explored.

Some aspects of cancer medicine.

The role of molecular oncology in understanding the nature of the cancer cell, and as an aid to diagnosis and even therapy, is discussed and illustrated with examples from commonly occurring malignancies. The appreciation of the importance of cell biology in explaining why cells become resistant to anticancer drugs has developed rapidly, and examples are given. Cell biology and molecular biology contribute to cancer prevention, which is becoming a practical possibility. Haemopoietic growth factors make it possible to give more intensive chemotherapy treatments and to improve the survival rate in patients with chemoresponsive disease. Intensification, however, has to be balanced against the risk of both short-term and, more seriously, long-term toxicity.

Testicular function following the treatment of Hodgkin's disease in childhood.

Testicular function was studied in 40 males treated in childhood for Hodgkin's disease at St Bartholomew's Hospital, and the Hospital for Sick Children, London, between 1971-1985. All patients were 16 years or over at evaluation, and off treatment more than 6 years. Basal FSH, LH and testosterone levels were measured. Testicular size was measured using a Prader orchidometer, and all patients were offered a seminal analysis. Twenty-eight patients were treated with chemotherapy, usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm. Twelve patients were treated with radiotherapy alone (five below the diaphragm). Twenty-six of 28 patients treated with chemotherapy and three of five patients treated with radiotherapy alone below the diaphragm have elevated basal FSH levels, and 18 of these also have elevated basal LH levels. Median testicular volume is 11 ml (range 5-25 ml). Eleven of 13 patients investigated are azoospermic. All patients have normal testosterone levels, and normal secondary sexual characteristics. There is no biochemical evidence of healing of the damaged germinal epithelium with elevated FSH levels persisting up to 17 years from the end of therapy. These results indicate a high incidence of damage to the germinal epithelium in patients treated with ChlVPP chemotherapy and/or radiotherapy below the diaphragm. Appropriate counselling of these patients with regard to their reproductive capabilities is essential.

Recombinant interferon-alpha 2b and high dose methyl prednisolone in relapsed and resistant multiple myeloma.

Twenty-one patients with refractory myeloma (10 primary resistant and 11 relapsed resistant) were treated with a combination of high dose methyl prednisolone and recombinant interferon alpha 2b (IFN-alpha 2b). This treatment included three megaunits/m2 of IFN-alpha 2b three times a week for 12 weeks, plus 5-day pulsed high dose methyl prednisolone every 3 weeks for two courses. A partial response (more than 50 per cent reduction in paraprotein) was observed in six patients; two of these had a greater than 75 per cent reduction in paraprotein, and evaluation of bone marrow showed <5 per cent plasma cells. A minimal response (more than 25 per cent reduction in paraprotein) was seen in four patients, giving an overall objective response rate of 10/21 (48 per cent). Subjective response, in terms of subsidence of pain and improvement of performance status, was seen in all patients who had adequate therapy. The protocol was generally well tolerated with minimal side-effects. There were 4/21 (19 per cent) treatment-related deaths which, though considerable, was anticipated in such a study population. The excellent subjective response seen supplements the objective response observed, and suggests a potential role for the combination of methyl prednisolone and IFN-alpha 2b in refractory myeloma.

Solitary plasmacytoma of bone--a rare disorder with an unusual evolution.

A 40 year old woman presented with a spinal epidural tumour, which on histology was shown to be a plasmacytoma. At that time she had no evidence of multiple myeloma. Ten months later, she developed a second isolated plasmacytoma in the spleen, for which she underwent splenectomy. Two years after her initial presentation she had another recurrence in the liver, followed by a full-blown picture of multiple myeloma. The myeloma was progressive and resistant to all forms of chemotherapy. She finally died of a massive gastrointestinal haemorrhage. The clinical features, natural evolution and management of solitary plasmacytomas are discussed.

Detection of Epstein-Barr virus in Reed-Sternberg cells of Hodgkin's disease arising in children.

Nonisotopic in situ hybridization has been used to investigate the role of Epstein-Barr virus (EBV) in the aetiology of pediatric Hodgkin's disease. Sections from 24 cases arising in children under the age of 15 years were hybridised with digoxigenin-labelled probes for both EBV and cytomegalovirus, and reactive sites were identified by a sensitive three-layer immunoperoxidase technique. EBV was identified in Reed-Sternberg and mononuclear Hodgkin's cells in five samples (21%). No samples were positive when the cytomegalovirus probe was employed. The specific identification of EBV in the malignant cells of Hodgkin's disease arising in children lends further support for a role of EBV in the aetiology of this disorder.

Outcome of children with resistant and relapsed Hodgkin's disease.

During the period 1974-89, 169 children with Hodgkin's disease were treated in the Paediatric Oncology Units of the Royal Marsden and St Bartholomew's Hospitals. The overall actuarial survival for the whole group was 81% at 10 years. Thirty-five of the 169 children either did not achieve a complete remission or subsequently relapsed. The estimated actuarial survival from initial relapse or failure of primary treatment was 60% at 5 years and 45% at 10 years. Over half of the patients requiring salvage therapy had declared themselves within 2 years and only 3 relapses occurred more than 3 years from diagnosis. Very few patients remain disease free long term after failure of primary and initial salvage therapy. Patients relapsing within a year of diagnosis or not achieving a complete response to primary therapy and those with disseminated relapse had a poor response to salvage therapy. A significant subgroup of patients had prolonged survival despite multiple relapses. Neither initial histology nor stage affected survival from relapse although numbers in each subgroup were small.

Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials.

PURPOSE: A meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma. METHODS: Meta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures. RESULTS: Overall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference in favor of CCT (P V .07). Comparison of the 2-year survival rates in the M + P treatment arms of each of the studies with available data showed an inverse correlation between survival and the proportion of patients with either poor performance status (P less than .001) or immunoglobulin A (IgA) M band (P = .02). CONCLUSIONS: These results imply that M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis. If reliable prognostic factors can be established for this disease, they could be used to select therapy for individual patients.

Platinum-based chemotherapy for recurrent CNS tumours in young patients.

Twenty nine patients (median age 12 years) with a CNS tumour, received platinum-based chemotherapy for assessable disease. In 23 patients there was an objective response with improvement lasting for a median duration of 11 months. There was little difference in the response to cisplatinum or carboplatin therapy. The response rates in specific disease groups were: medulloblastoma 8/10, two with a complete response (CR) and six with a partial response (PR); ependymoma 1/5 PR; pineal retinoblastoma 5/5 with three CR and two PR; primitive neurectodermal tumours (PNET) 2/2 PR and pineal germ cell tumours 6/6 with four CR and two PR. It is concluded that platinum-based chemotherapy has a beneficial effect on CNS tumours of the CNS, especially medulloblastoma, ectopic intracranial retino-blastoma and pineal germ cell tumours.