Clinical validation of an autoantibody test for lung cancer.

BACKGROUND: Autoantibodies may be present in a variety of underlying cancers several years before tumours can be detected and testing for their presence may allow earlier diagnosis. We report the clinical validation of an autoantibody panel in newly diagnosed patients with lung cancer (LC). PATIENTS AND METHODS: Three cohorts of patients with newly diagnosed LC were identified: group 1 (n = 145), group 2 (n = 241) and group 3 (n = 269). Patients were individually matched by gender, age and smoking history to a control individual with no history of malignant disease. Serum samples were obtained after diagnosis but before any anticancer treatment. Autoantibody levels were measured against a panel of six tumour-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2). Assay sensitivity was tested in relation to demographic variables and cancer type/stage. RESULTS: The autoantibody panel demonstrated a sensitivity/specificity of 36%/91%, 39%/89% and 37%/90% in groups 1, 2 and 3, respectively, with good reproducibility. There was no significant difference between different LC stages, indicating that the antigens included covered the different types of LC well. CONCLUSION: This assay confirms the value of an autoantibody panel as a diagnostic tool and offers a potential system for monitoring patients at high risk of LC.

Immunotherapy in the management of myelogenous leukemia.

Now that it has been clearly established that tumor-associated antigens exist in acute leukemia in man, as in animals, the possibility of stimulating the patient's immune system to react against them arises. In animal experiments the most effective method of influencing the progress of leukemia after the implantation of living malignant cells has been a combination of nonspecific stimulation of the reticuloendothelial system, with agents such as BCG or Corynebacterium parvum, either with chemotherapy or with specific immunization with irradiated leukemic cells. However, such treatment is only effective if the number of living malignant cells is small as it takes a powerful immune response to overcome even a small number of malignant cells. It is for these reasons that most of the studies in man have been on patients with acute leukemia in remission. Mathé, in 1969, produced evidence that BCG and irradiated allogenic leukemia cells could lengthen the duration of remission in ALL in children. However, later results of intensive combination chemotherapy, together with prophylactic treatment of the central nervous system by Pinkel and his colleagues, were so encouraging that immunotherapy is not felt to be needed and therefore is not being extensively used in this form of leukemia at the moment. The situation in AML, particularly in adults, is completely different. The maintenance of remission with chemotherapy in this type of leukemia is difficult and relapses occur quite rapidly. Various centers have now shown that both remission lengths and overall survival are significantly prolonged by using BCG with or without irradiated allogenic leukemia cells.

Blast crisis of chronic myeloid leukaemia: the effect of intensive chemotherapy.

24 patients with Philadelphia chromosome positive chronic myeloid leukaemia (CML) in blast crisis were treated with intensive chemotherapy. 16 patients showed either partial or complete response to this treatment, but median survival remained short (13 weeks), and much of this time was spent in hospital. These results were not significantly better than those obtained by others using vincristine and prednisolone alone, and this combination of drugs can often be given on an outpatient basis. It is concluded that until more effective intensive therapy becomes available patients in CML blast crisis should be managed in such a way that the quality of life is not impaired; and that at present vincristine and prednisolone appears to be the most impaired; and that at present vincristine and prednisolone appears to be the most appropriate initial treatment, though even this is far from satisfactory.

Hypoplastic acute myelogenous leukaemia.

The clinical course, diagnosis and management of nine cases of hypoplastic acute myelogenous leukaemia are described. Such cases may follow a slowly progressive course and should not receive anti-leukaemic chemotherapy unless the disease is advancing rapidly or unless some specific complication develops. If chemotherapy has to be given, usually because of severe and recurrent infections, then prompt and prolonged remission of disease may occur.

Immunotherapy for acute myelogenous leukemia.

One hundred and seven untreated patients with acute myelogenous leukemia (AML) were admitted to St. Bartholomew's Hospital between the 10th October 1970 and the 31st January 1973. Before receiving drugs to induce remission they were allocated alternatively into 2 groups to decide their remission treatment, a group to receive chemotherapy alone and a group to receive the same chemotherapy with immunotherapy. The patients were then given induction chemotherapy and 45 of them attained complete remission. All patients in remission then received chemotherapy consisting of 5 days treatment every 28 days. Patients receiving immunotherapy were also given multiple weekly intradermal injections of irradiated stored AML cells and Glaxo BCG using a Heaf gun. There were 19 patients in the group which received only chemotherapy during remission; 7 of these patients remain alive (median survival after attaining remission--303 days) and only 5 are still in their first remission (median remission length 188 days). Twenty three patients were allocated to receive immunotherapy during remission in addition to chemotherapy and 16 remain alive (median 545 days) and 8 are in their first remission (median 312 days). The difference in survival of the 2 groups is significant with a sigma value of 0.003.

Safe method of collecting leukaemia cells from patients with acute leukaemia for use as immunotherapy.

Leukaemia cells were collected from the blood of 72 untreated patients using a continuous-flow blood cell separator. The yield of cells was proportional to the number circulating in the patient, and up to 1 x 10(12) could be obtained in three hours. Complications of the procedure were mild, consisting of chills and shivering in 18% of patients. Leucopheresis at the time of diagnosis is an essential part of setting up a specific immunotherapy programme for patients with acute myelogenous leukaemia, and the lack of harmful side effects makes the collection of these cells ethically justified. The need for a centralized service to provide cells for this form of therapy is emphasized.

Immunotherapy for acute myelogenous leukaemia.

One hundred and seven untreated patients with acute myelogenous leukaemia (AML) were admitted to St Bartholomew's Hospital between 10 October 1970 and 31 January 1973. Before receiving drugs to induce remission they were allocated alternatively into 2 groups to decide their remission treatment-a group to receive chemotherapy alone and a group to receive the same chemotherapy with immunotherapy. The patients were then given induction chemotherapy and 45 of them attained complete remission. All patients in remission then received chemotherapy consisting of 5 days treatment every 28 days. Patients receiving immunotherapy were also given multiple weekly intradermal injections of irradiated stored AML cells and Glaxo B.C.G. using a Heaf gun. There were 19 patients in the group which received only chemotherapy during remission; 7 of these patients remain alive (median survival after attaining remission 303 days) and only 5 are still in their first remission (median remission length 188 days). Twenty-three patients were allocated to receive immunotherapy during remission in addition to chemotherapy and 16 remain alive (median 545 days) and 8 are in their first remission (median 312 days). The difference in survival of the two groups is significant with a P value of 0·003.

Management of adult acute myelogenous leukaemia.

Consecutive adult patients admitted to St. Bartholomew's Hospital with acute myelogenous leukaemia have been treated with a remission induction drug schedule consisting of daunorubicin and cytosine arabinoside. Intermittent five-day courses were used in 72 patients, and a complete remission was obtained in 39 patients (54%). An alternative drug schedule in 22 patients resulted in fewer remissions but this may have been due to age differences in the two groups. Age and initial platelet count were found to be important factors in determining the success of remission induction therapy; the older patients and those with low platelet counts responded less well.A series of 23 patients who achieved remissions was divided into two groups; one received intermittent combination chemotherapy as the only form of maintenance, and the other was given weekly immunotherapy in addition to the chemotherapy. The immunotherapy consisted of irradiated allogeneic leukaemic cells and B.C.G. Eight of the 10 patients on chemotherapy alone have already relapsed compared with five out of 13 patients in the immunotherapy group. It is hoped that these promising initial results with this form of maintenance will be confirmed as more patients enter the maintenance trials.