Platelets play a central role in primary hemostasis. The role of the coagulation mechanism during early stages of hemostasis is less clear, although increasing evidence is emerging indicating the ultimate importance of the factor VII (FVII)-tissue factor-dependent coagulation system in providing the first thrombin molecules necessary for the platelet activation to occur. Supporting this, early fibrin formation has been reported to occur within the bleeding time wound and infusion of recombinant FVIIa (rFIIa) has been shown to shorten the bleeding time in rabbits. We have investigated whether infusion of rFVIIa would enhance fibrin formation in bleeding time wounds in patients with thrombocytopenia as reflected by a shortening of the bleeding time. A reduction of the bleeding time was found in 55/105 cases (52%). The decrease was significantly more pronounced when the platelet count exceeded 20 × 10⁹/l. With the exception of an anaphylactoid reaction in 1 patient, no major adverse reactions related to the study drug were observed. Nine infusions of rFVIIa were given to 8 thrombocytopenic patients with overt bleeding. One patient received two infusions. Bleeding decreased in all patients and stopped in 6 patients.

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.

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Serum β2‐microglobulin (S‐β2m) was measured at diagnosis in 189 patients with malignant lymphoma, all with a normal serum creatinine clearance. The diagnosis was non‐Hodgkin's lymphoma (NHL) in 149 patients and Hodgkin's disease (HD) in 40. Among the NHL group, S‐β2m was raised (>3.0 mg/1) in 15% of patients with Stage I and II and in 65% of those with Stage III and IV. The corresponding frequencies for HD were 11% and 83% respectively. In NHL, a high pretreatment level of S‐β2m was found to be a poor prognostic sign in all stages. Patients in Stage I and II with an elevated pretreatment level of S‐β2m had a higher relapse rate than those with normal S‐β2m. In Stage III and IV patients with initial levels > 3.5 mg/l, the survival was significantly shorter than in those with initial values of <3.5 mg/l. A lower mean S‐β2m value was found in Stage III and IV patients who achieved complete remission than in those who did not. Serial determinations of S‐β2m in 23 patients with NHL showed that increased pretreatment levels became normal when remission was achieved and increased again in relapse. Thus the S‐β2m provides valuable prognostic information in this group of patients.

Philadelphia-chromosome metaphases in 57% of the patients (7% became Phnegative). The corresponding ngureS after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotrausplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month rreatmen~ Ph-analysis was performed. Patients with Press 1066-5099/93/$5.00/0 after ABMT due to interstitial pneumonia. Of the remaining 79 patients, 32 are in continuous chronic phase, 34 were allotramplanted and 13 have died (three during Daunorubicin Ara-C [DA]) treatment, one refusing transfusions, nine in blastic transformation). We conclude that intensive treatment effectively reduces the Ph-positive clone in CML. Bone marrow can remain Ph-negative for 32+ months after ABMT. A long follow-up is needed to see whether this treatment prolongs time to metamorphosis.