Prospective randomised study of double hemi-body irradiation with and without subsequent maintenance recombinant alpha 2b interferon on survival in patients with relapsed multiple myeloma.

Immediately before first hemi-body irradiation, 59 patients with relapsed multiple myeloma were randomised to receive or not to receive subsequent alpha-2b interferon maintenance. 13 patients (22%) [8 of 31 (26%) controls, 5 of 28 (18%) in the interferon arm] received single hemi-body irradiation alone due to progressive disease and/or persistent cytopoenias following the initial procedure. Mean time between upper and lower hemi-body irradiation was 69 days (range 35-294). Of 23 patients randomised to receive interferon and completing double hemi-body irradiation, 15 (65%) achieved peripheral blood counts adequate to allow interferon administration as per study criteria commencing at a mean 116 days (61-241) from time of study entry. The mean period of interferon therapy, starting at a mean 65 days (26-160) post second hemi-body irradiation, is 16.4 months (2-33.5). There was no significant difference in median survival durations (10 months) from time of initial radiotherapy between control and interferon patients.

Autologous bone marrow transplantation in multiple myeloma: a single centre experience of 23 patients.

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma.

In view of increasing controversy regarding the role of double hemibody irradiation (DHBI) in the treatment of multiple myeloma, we have analysed the use of this technique at our institution over a 6-year period. Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemoresistant to initial therapy. Fifteen patients received alpha IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week, as part of a randomized trial. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. alpha IFN did not appear to prolong survival (OS or PFS) post-DHBI. Cytopenia was a significant problem, such that only 60% of patients had counts adequate enough to be eligible for alpha IFN. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

An assessment of the comparative utility of functional and molecular level analyses in the investigation of patients with thrombophilia.

Aim-To determine the relation of the low anticoagulant response phenotype with the Factor V Q506 (Leiden) mutation in a cohort of patients with thrombophilia.Methods-Fifty four patients with either a personal or family history of deep vein thrombosis were investigated both for their anticoagulant response by the activated protein C resistance test (APCR) and their genetic status in respect of the Leiden mutation by means of a PCR-RFLP method.Results-Low APCR ratios do not necessarily predict possession of the Leiden mutation. Conversely, normal ratios do not exclude the mutation. Of 14 individuals with low APCR ratios, the Leiden mutation was absent in five. Of the remainder, three were heterozygous and six homozygous. Of nine heterozygote individuals, only three had low APCR ratios. All patients homozygous for the defect had low APCR ratios.Conclusions-These results lend further weight to the hypothesis that the APC resistant phenotype results from more than one genetic defect and indicate the value of combined functional and molecular investigations in all patients with thrombophilia.

Low-dose recombinant alfa-2a-interferon: a feasible maintenance therapy in acute myeloid leukaemia in the older patient.

Eleven patients with acute myeloid leukaemia (AML) in first complete remission (CR) were treated with alfa-2a-interferon (for short 'interferon') maintenance therapy, at a dose of 3 MU twice to thrice weekly subcutaneously. Adjustments were made to maintain neutrophil counts > 1 x 10(9)/l and platelet counts > 100 x 10(9)/l. A transient fall in haemoglobin, neutrophil and platelet counts was noted in all 9 evaluable patients. Median time to nadir was 7 weeks. Initial dosage reductions were necessary in 5 patients, 3 of whom were later able to tolerate the starting dose. No episodes of infection or bleeding were documented during therapy and no red cell or platelet transfusions were necessary. At the time of writing (median follow-up of 31 weeks), 7 patients continue in CR, 6 of whom remain on interferon. One patient discontinued interferon on developing sicca syndrome. Other than in this patient, side effects were minor. Mean dose administered was 6.7 MU/patient/week. We conclude that low-dose IFN maintenance therapy is well tolerated in older patients with AML in first CR.

Recombinant interferon alfa 2a in the treatment of patients with early stage B chronic lymphocytic leukaemia.

18 patients with early stage, previously untreated B-CLL were given interferon alfa (IFN alpha) 2a. 3 MU thrice weekly, subcutaneously. The peripheral lymphocyte count decreased in all patients. Response was delayed in three patients until they had received a median of 5 months therapy, one of whom had an initial transient increase in lymphocytes. Two patients normalized their blood lymphocyte counts, but neither achieved complete remission (CR). Responses were transient in eight patients lasting a median of 5 months (3-21). Binding anti-IFN alpha antibodies were present in 9/17 patients tested (53%). Low titre binding antibodies (< 533 IBU/ml) were not associated with LHR, but high titre antibodies (> 4401 IBU/ml) were. Two of 12 patients assessed had a > 3 g/l increase in baseline serum IgG levels during IFN alpha therapy, one of whom reverted to pretreatment levels in association with LHR. Haematological toxicity was moderate, other than in two patients, one of whom developed autoimmune haemolytic anaemia and the other thrombocytopenia. We conclude that IFN alpha lowers the lymphocyte count in early stage CLL, that the response may be delayed and that anti-IFN alpha antibodies may play a role in a proportion of those in whom the response is transient.