Ann-Mari Udén

Comparison of daunorubicin and daunorubicin-DNA complex in the treatment of acute nonlymphoblastic leukemia

SummarySixty consecutive patients, 15–60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1+ARA-C 2 mg/kg body weight on days 1–5; R2, DNR 1.5 mg/kg on days 1 and 2+ARA-C 2 mg/kg on days 4–8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2+ARA-C 2 mg/kg on days 4–8. Maintenance treatment consisted of monthly courses of DNA 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1–5, alternating with thioguanine 2 mg/kg PO on days 1–5 combined with ARA-C 1 mg/kg IV on days 1–5. Fourteen patients of 20 went into complete remission with R1, 13 of 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer ‘minor’ cardiac abnormalities than treatment with free DNR in the same dosage schedule.

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: A preliminary report

SummaryForty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1+ARA-C on days 1–5; R 2 = courses of daunorubicin on days 1 and 2+ARA-C on days 4–8; R 3 = courses of daunorubicin-DNA complex on days 1–2+ ARA-C on days 4–8.Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.

Intensive Treatment in order to Minimize the Ph-Positive Clone in Chronic Myelogenic Leukemia

Several studies indicate that interferon (IFN) treatment, intensive chemotherapy and autologous bone marrow transplantation (ABMT) effectively reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients < or = 55 years, we have combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a status of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After six months of treatment, Ph-analysis was performed. Patients with Ph-positive cells in bone marrow then received 1-3 courses of intensive chemotherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1993, 97 patients were registered in the study. Six months of IFN+HU reduced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotransplanted. 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 after ABMT due to interstitial pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukotriene biosynthesis by polymorphonuclear leukocytes from two patients with chronic granulomatous disease.

Polymorphonuclear leukocytes (PMNL) isolated from two patients with chronic granulomatous disease (CGD) were tested for their ability to metabolize arachidonic acid to lipoxygenase products including 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4). Analyses of incubations of these PMNL with arachidonic acid and the calcium ionophore A23187 did not differ from simultaneous controls in the production of LTB4, other 5,12-dihydroxy-eicosatetraenoic acids, or monohydroxy-eicosatetraenoic acids. The clinical diagnosis of CGD was confirmed in both cases by determination of PMNL chemiluminescence. Leukocytes from both patients failed to generate active oxygen species in response to either LTB4 or formyl-methionyl-leucyl-phenylalanine. The observation of arachidonic acid oxidation in the absence of superoxide anion precludes a role for the active oxygen species in this metabolic process. These studies clearly dissociate the ionophore-induced leukocyte respiratory burst from the oxidation of arachidonate to the leukotrienes. In addition, the defect of CGD appears to be unrelated to the ability of PMNL to carry out arachidonate oxygenation.

Therapeutic Effects of Low-Dose Cytosine Arabinoside, α-Interferon, 1,25-Dihydroxyvitamin D3 and Retinoic Acid in Myelodysplastic Syndromes and Acute Leukemia

Fifty-six patients with myelodysplastic syndrome or with acute leukemia were treated with low-dose Ara-C, a combination (IDR) of α-interferon, 1,25-dihydroxyvitamin D3 and retinoic acid or a combination of all drugs. Complete remissions were obtained only when treatment included Ara-C, but long-lasting and clinically stable partial remissions and significant responses were achieved in 7 of 16 patients treated with IDR. Bone marrow hypoplasia was not necessary for remission in any of the treatment groups. Our data indicate that these substances exert their action via mechanisms different from those seen in conventional chemotherapy. Possible mechanisms involve tumor-cell differentiation, a slow-acting cytotoxicity or a combination of these two mechanisms.