A randomized study of VAD therapy with either concurrent or maintenance interferon in patients with newly diagnosed multiple myeloma.

This randomized study was designed to determine whether response to VAD chemotherapy could be prolonged by using rh alpha-2b-interferon (IFN) at a dose of 3 mU three times per week, either concurrently with VAD (VIC) or as maintenance after completion of VAD (VIF). Maintenance IFN was given for 9 months in order for the duration of IFN therapy to be similar in both groups. 72 patients were randomized between December 1988 and August 1993. The majority of patients had poor prognostic features. The objective response rate was similar in each arm, 78% in VIF and 77% in VIC. Of the 56 responders, 33 have relapsed, three died in remission, and 18 proceeded to high-dose therapy, withdrew for other reasons or were lost to follow-up and were censored from analysis at the relevant time point. Only two patients remain in remission (both in partial remission). Median PFS was 15 months for both VIF and VIC, compared with 16.5 months for a historic control group treated with VAD alone (n.s.). The estimated median survival in VIF was 43 months and in VIC 22 months, compared with 45 months in the historic controls (n.s.). These findings indicate that neither maintenance nor concurrent IFN prolongs response to VAD.

Platelet and coagulation studies in Ehlers-Danlos syndrome.

Fifty-one patients with Ehlers-Danlos syndrome were investigated for abnormalities of platelets and coagulation. Thirty-eight were examined prospectively and 13 retrospectively. A bleeding history was taken from all patients; only four (8%) gave no history of a bruising or bleeding tendency. Nine patients (18%) had significant haemostatic abnormalities of whom four (8%) had a platelet release defect, three (6%) had a factor XI deficiency and two (4%) had a factor XIII deficiency. Additionally 16 patients (31%) had mild abnormalities of uncertain significance of whom four (8%) had prolonged bleeding times (three in association with platelet aggregation abnormalities), 13 (26%) had platelet aggregation abnormalities and two had a positive Hess test. Twenty-four patients (47%) had normal tests for haemostasis of whom 20 (39%) had a bleeding diathesis and four (8%) had no such tendency. Results were analysed according to the type of Ehlers-Danlos syndrome, but there was no pattern to the abnormalities. The high frequency of a bleeding tendency in Ehlers-Danlos patients with normal tests for haemostasis (83%) supports the conventional explanation for this clinical feature, that defects in the structural integrity of skin and blood vessels lead to easy bruising.

Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma.

32 previously untreated patients with multiple myeloma received vincristine, doxorubicin ('Adriamycin'), and dexamethasone (VAD) as first-line therapy. The overall response rate was 84%, with 28% of all patients entering complete remission. Response was rapid, with near-maximum response occurring after two courses of treatment and rapid improvement in bone-marrow function. Median response duration was 18 months and this seemed to be unaffected by initial prognostic criteria or by degree of remission achieved. The projected median survival was 44 months, with 75% of all patients and 83% of responders being alive at 2 years. Side-effects due to steroids were common, but there was only 1 treatment-related death. The high response rate and lack of toxicity offer an advantage over other forms of initial treatment, although other strategies will be necessary to prolong the duration of response.

Pulmonary permeability in hematologic malignancies. Effects of the disease and cytotoxic agents.

Pulmonary permeability was assessed using the technique of DTPA aerosol transfer in untreated patients with chronic lymphocytic leukemia (CLL) and in patients with a variety of hematologic malignancies that had all been treated with alkylating agents. Two findings emerged: In the untreated CLL patients, the permeability of the upper and middle lung regions was reduced. This may be due to diffuse infiltration by the CLL; and Treatment with cytotoxic agents increased epithelial permeability in both middle and lower lung regions. Further prospective studies are required to determine the cause of the long T50 values in untreated CLL and to confirm that the DTPA transfer test is a sensitive indicator of the damage which eventually leads to pulmonary fibrosis.

Whole blood viscosity in polycythaemia: the effect of iron deficiency at a range of haemoglobin and packed cell volumes.

The effect of iron deficient red cells changes (MCH range 20.0-32.6 pg) on whole blood viscosity (WBV) at high and low shear rates (94.5 and 0.51 s-1), has been assessed at a wide range of standardized PCV (0.30-0.65) and standardized Hb values (10.0-22.0 g/dl). Particular attention was given to the precision of PCV measurement. At all PCV values there was no correlation between MCH and WBV, whereas at all Hb values there was a significant negative correlation between MCH and WBV. If the treatment of polycythaemia is by venesection, iron deficient red cell changes occur frequently. These changes are unimportant if control of the WBV is the objective of treatment, as long as the PCV is accurately measured. Alternatively, in the secondary polycythaemias, where oxygen saturation is reduced, the induction of iron deficient red cell changes could be regarded as disadvantageous since at a standard PCV of 0.50 the Hb and hence oxygen carrying capacity is reduced by approximately 11% between MCH values of 30 and 20 pg.

Primary thrombocythaemia treated with busulphan.

Thirty-seven patients with primary thrombocythaemia (PT) treated with busulphan have been followed for periods up to 25 years. Reduction of the platelet count to less than 400 X 10(9)/l resolved vascular occlusive symptoms, but haemorrhagic symptoms often remained unaltered. Cox regression analysis indicated that there were only two prognostically important presenting features; age had a strong inverse correlation with survival and vascular occlusive symptoms correlated with a better survival. Median duration of survival on treatment was 9 X 8 years. The number of deaths was 2 X 1 times that of a comparable control group, with deaths from myelofibrosis markedly increased. Deaths from thrombosis and malignant diseases, including leukaemia, were not significantly different from the number expected, which emphasizes the efficacy and the relative safety of busulphan for the long-term treatment of PT. Progression of PT into myelofibrosis occurred in 24% of cases and 9% became polycythaemic. Two additional cases of "thrombocythaemia' with a Philadelphia chromosome (and no overt evidence of chronic granulocytic leukaemia) are also presented.

Cutaneous periarteritis nodosa. Hepatitis B surface antigen-containing immunocomplexes and polymorphonuclear-leukocyte lysosomal enzyme release.

In a patient with cold-induced cutaneous periarteritis nodosa, cryoprecipitation of a circulating hepatitis B surface antigen-containing immunocomplex resulted in phagocytosis by neutrophils and monocytes with prominent vacuolation of the cells and extracellular release of lysosomal enzymes. We believe this immunocomplex attached itself to the cell membrane and induced vacuolation and degranulation in normal neutrophils.

Exchange transfusion in life-threatening sickling crises.

Five patients are reported with sickle cell syndromes (HbSS, HbSC and HbSthal) in whom rapid exchange transfusion led to resolution of life-threatening infarctive crises. The technique appears to be of value in the management of severe complications of sickle cell syndromes.