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26 of 32 patients with multiple myeloma (MM) were successfully tested in vitro for human leucocyte interferon (IFN) sensitivity by use of the human tumour stem cell assay (HTCA) and/or 3H-thymidine incorporation (LI). Altogether, 12 patients were sensitive to IFN in vitro and 14 were resistant. All patients received treatment with leucocyte IFN. 8 patients were classified as responders, 3 as partial responders and 15 as non-responders. Correlating the in vitro/in vivo results, we found that the in vitro tests of the myeloma cells reflected a true sensitivity in 9 patients (75%) and a true resistance in 12 patients (86%). Furthermore, stimulation by IFN was found in 9 in vitro tests, of which 8 were obtained from non-responsive patients. Our results show that in vitro testing for IFN sensitivity is of clinical importance in predicting response to IFN treatment. Also, a stimulating effect by IFN in vitro will imply an unfavourable response in vivo.

Eighty-one previously untreated patients with multiple myeloma stage II entered a randomized trial comparing oral melphalan (0.25 mg/kg/day; n = 40) with intravenous melphalan (0.125 mg/kg/day; n = 41) in combination with oral prednisone (2 mg/kg/day). The courses were given for 4 days and repeated every sixth week. The treatment groups were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, the response duration times and the survival times. No significant difference in non-hematological and hematological toxicity was noted. Since intravenous administration of melphalan did not result in a substantial increase in response rate or survival, this study supports the use of oral melphalan/prednisone as first-line therapy for patients with multiple myeloma.

The analysis of individual biochemical and clinical variables in 121 patients with multiple myeloma showed that serum beta 2-microglobulin (S-beta 2m) had the most significant relation to survival. Other variables such as serum thymidine kinase (S-TK), serum lactate dehydrogenase (S-LDH), S-creatinine, haemoglobin (Hb), ESR, S-albumin, age and clinical stage were also significant. No such relationship was found with M-component, presence of light chains in urine, type of secreted immunoglobulin or S-calcium. The exclusion of clinical stage in the first multivariate analysis resulted in a model consisting of S-beta 2m, age and S-TK, none of the other variables gave additional information. When in the second multivariate analysis the basic variables involved in staging procedure were excluded and clinical stage included, stage III, but not stage II, was found to give additional information to the model described above. Individual analysis of the variables showed that Hb had the most significant relation to effect of initial therapy. Other significant variables were S-TK, S-beta 2m and age. When using the multivariate approach, Hb alone was found to contain all the relevant information.

Serum beta 2-microglobuline (S-beta 2m) was evaluated in 121 untreated patients with multiple myeloma. Values greater than 3 mg/l were found in 82% of the patients. Mean S-beta 2m values of the total group of patients correlated with clinical stage. However, there was no correlation if values were corrected for S-creatinine. Seventy-nine patients had normal (less than or equal to 106 mumol/l) and 52 patients abnormal S-creatinine. Patients with S-beta 2m values below 7 X 6 mg/l had an estimated median survival of 44 months compared to 12 months for patients with levels above 7 X 6 mg/l. If S-beta 2m values in patients with normal S-creatinine were combined with values corrected for S-creatinine from patients with elevated S-creatinine a beta 2m cut off level of 6 X 6 mg/l gave a median probable survival of 43 months compared to 14 months. We conclude that pretreatment S-beta 2 microglobulin is a useful marker for predicting survival in multiple myeloma. The problem of the relationship between S-beta 2m and S-creatinine is discussed.

Serum lactic dehydrogenase (S-LDH) was analysed at diagnosis in ninety-three patients with multiple myeloma. The patients were then followed up after a mean observation period of 39 months (SD 29). Serum lactic dehydrogenase was elevated in twenty-seven out of ninety-three patients and found to correlate with the serum concentrations of beta 2-microglobuline, creatinine, and thymidine kinase. In discriminant analysis of pretreatment S-LDH levels in relation to survival, the best discrimination level was 7.0 mukat 1(-1). Patients with values below 7 microkat 1(-1) ahd a median survival time of 45 months compared to 14 months for those with levels above 7 mukat 1(-1) (P less than 0.001). Serum lactic dehydrogenase at diagnosis, thus, has prognostic information in multiple myeloma.

Four patients with myelomatosis (one IgG-x-type, two IgA-x, and one Bence-Jones-x) were given human leucocyte interferon as the only treatment for from 3 to 19 months. Remission was complete in two patients and partial in the other two. Normal bone-marrow haematopoiesis was slightly inhibited. The disease has not so far progressed in any of the patients.

Subpopulations of human T lymphocytes were analysed by monoclonal antibodies (OKT3, OKT4, OKT8) in healthy controls and in patients with multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM) and benign monoclonal gammopathy (BMG). Lymphocytes forming rosettes with SRBC correlated well with T cells staining in indirect immunofluorescence by OKT3 monoclonal antibodies. The relative and absolute numbers of OKT4+ T cells were significantly lower in patients than in controls. Though, the percentage of OKT8+ T cells was increased in patients, the total OKT8+ cell counts were normal in all patient groups. The ratio between OKT4+ and OKT8+ lymphocytes was low in the groups of treated MM and of WM patients compared to controls (P less than 0.001). Moreover, the ratio was lower than the normal range in 27% of BMG and 38% of untreated MM patients. The imbalance between OKT4+ and OKT8+ T cells in untreated MM was more pronounced in clinical stage III patients than in stage I and II patients. The most pronounced changes were noted in treated MM patients. The significance of the altered T cell subsets in monoclonal gammopathies with regard to polyclonal and tumor B cell regulation remains to be established.

We have treated 10 patients with hairy-cell, or hairy-cell-like leukaemia, for more than 6 months, with alpha interferon 3 X 10(6) IV/day I.M. or subcutaneously. All patients were severely pancytopenic before treatment. 7 patients had a typical hairy-cell leukaemia, whereas 3 lacked hairy cells but had the characteristic bone-marrow infiltration. The peripheral blood counts improved in all patients during treatment and the lymphoid infiltration of the bone-marrow was shown to decrease. 1 patient obtained complete remission, 6 partial remission and 3 had a minor response. It is concluded that alpha interferon is effective in the treatment of patients suffering from hairy-cell leukaemia.

Summary. A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, β2-microglobulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (> 5·1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.

Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.

IgA subclass distribution in the serum of 40 patients with IgA multiple myeloma and 10 patients with benign monoclonal gammopathy of the IgA class was determined. All were found to be of the IgA 1 subclass. A review of the literature shows a marked predominance (93%) of IgA 1 paraproteins, suggesting an under-representation of IgA2 myelomas. The subclass pattern in 11 double paraproteinemias studied and those previously reported in the literature suggest a pattern of IgG1 - IgA1, IgA1 - IgG4 and possibly also IgG2 - IgA2 switches in malignant cells.