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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.

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.

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.

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.

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.

The total concentrations of alpha(2) globulin and two of its components, haptoglobin and caeruloplasmin, have been determined in the sera from 78 patients with primary malignant diseases of lympho-reticular tissue (reticuloses). The total alpha(2) globulin fraction was significantly raised only in Hodgkin's disease. The serum haptoglobin was also significantly increased in Hodgkin's disease and some other reticuloses, including acute leukaemia, lymphosarcoma, and reticulum cell sarcoma. The serum level of caeruloplasmin was raised in all reticuloses. There was possibly some correlation between the rise in haptoglobin and caeruloplasmin concentrations and the total alpha(2) globulin in Hodgkin's disease but this was not statistically significant. The significance of these results is discussed, and it is concluded that the increase in alpha(2) globulin which occurs in Hodgkin's disease is due to an increase in several of its components and not to a single component.

L-Asparaginase was used to treat 40 patients with acute leukaemia or lymphosarcoma. Fifteen with acute lymphoblastic leukaemia either untreated or in relapse after previous therapy were given "Squibb," "Bayer," or "Porton" L-asparaginase. Five of these patients had complete remission of their disease, and four had good partial remission. Eleven patients with acute myeloid leukaemia were treated for a short period with L-asparaginase alone. None of them went into remission though a pronounced fall in the numbers of circulating white cells was seen. Six patients with lymphosarcoma received L-asparaginase, two of them having good partial remissions.The toxic side-effects of the L-asparaginase from the three sources seemed to vary, and L-asparaginase from Erwinia carotovora appeared to be antigenically different from the enzyme produced by Escherichia coli.The way in which leukaemic cells become resistant to the action of the enzyme requires further investigation. To overcome this resistance asparaginase should be used in combination with other drugs in the treatment of acute leukaemia.

Biopsy specimens and sera were obtained from 103 melanoma patients. Autoantibodies were demonstrated by (1) complement-dependent cytotoxicity of autologous melanoma cells in short-term culture; (2) complement-dependent inhibition of ribonucleic acid synthesis; (3) immunofluorescent staining of the cytoplasm of killed melanoma cells and of the surface membrane of viable melanoma cells. Over one-third of the sera studied had antibodies to autologous melanoma cells. Although for technical reasons all three tests could not be performed with the cells from every melanoma, whenever multiple testing was possible there was complete concordance. The autoantibodies were virtually confined to patients in whom the disease was not widely disseminated, and over 80% of such patients had positive sera. In a limited number of patients who have been followed autoantibodies disappeared as the disease progressed to become widely disseminated. Two patients with generalized disease developed autoantibodies following inoculation by their own irradiated tumour cells.TWO TYPES OF AUTOANTIBODIES WERE RECOGNIZED: one, active against antigen(s) in the cell surface membrane, was specific for each tumour-that is, only the autologous serum reacted-and was concerned in the cytotoxic activity; the other reacted with cytoplasmic antigens which appeared to be present in most or all melanoma cells.

Leukaemia cells in the peripheral blood of nine patients with acute leukaemia were removed and stored. When the patients had been brought into haematological remission these leukaemia cells were cultured with autologous lymphocytes both before and after the patients had been autoimmunized with their own irradiated leukaemia cells. The extent to which the leukaemia cells stimulated the "normal lymphocytes" was increased as the result of autoimmunization.The implications of the use of this test for determining the best regimen for "immunotherapy" in acute leukaemia are discussed.

Thirteen patients have been immunized with their own irradiated melanoma cells on one or more occasions. Following these autografts tumour-specific cytotoxic antibodies were produced, the longest response lasting 14 days. This procedure had no apparent effect on the course of the disease in these patients.

A combined morphological and metabolic study has been made of the lymphoid cells in the blood during the immune response in man. Similar changes were observed in both primary and secondary responses to a number of different microbial antigens. The cellular response involved an increase in numbers of three types of cell; hyperbasophilic medium lymphocytes, plasma cells, and large lymphoid cells. The large lymphoid cells were about 20 micro in diameter with large nuclei, prominent nucleoli, and an intensely basophilic cytoplasm with numerous polyribosomes. About 30% of these cells were in the DNA synthetic phase of cell growth. Electron microscopy has shown that many of the basophilic medium-sized cells have sufficient well-organized endoplasmic reticulum to be included in the plasma cell series. The hyperbasophilic cells labeled more heavily with tritiated uridine and tritiated leucine than the normal small and medium lymphocytes from the peripheral blood of patients not under antigenic stimulation. The evidence in this paper supports the argument that the atypical mononuclear cells first described by Türk and others in the blood of patients with infections are immunoblasts, plasma cells, and other reactive lymphoid cells representing a circulating population of lymphoid cells derived from lymphoid tissue responding to antigenic stimulation. The presence of such cells may be a valuable indication that an immunological reaction is in progress when direct proof is lacking.

The lymphoid cell population in the peripheral blood in Hodgkin's disease differs from normal blood in three ways. Firstly, the number of large lymphoid cells actively synthesizing deoxyribonucleic acid is increased; secondly, the number of medium-sized lymphoid cells with intensely basophilic cytoplasm is increased; and, thirdly, occasional plasma cells are seen. These changes are related to the activity but not to the stage of the disease.Similar changes are found under conditions of known antigenic challenge-that is, in infections, and after immunization, and in rheumatoid arthritis and systemic lupus erythematosus.

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.