Salvage therapy of refractory and relapsed acute leukemia with high dose mitoxantrone and high dose cytarabine.

We have assessed the outcome of 66 refractory and relapsed acute leukemia patients treated with high dose mitoxantrone and cytarabine. Therapy consisted of a total dose of 40-60 mg/m2 mitoxantrone and 3 g/m2 of cytarabine daily on 5 consecutive days. A total of 28 patients were treated for primary resistant and 38 patients for early or late relapsed leukemia. A total of 35 patients achieved CR. Four patients died during the induction course. Toxicity was acceptable and comparable to other salvage regimens. The median disease-free and overall survivals were 4 and 6 months, respectively. Although this regimen is effective in achieving remission in refractory leukemia, its duration is short.

Transient normal platelet counts and decreased requirement for interferon during pregnancy in essential thrombocythaemia.

We report on the remarkable decrease in the platelet counts during pregnancy in two women with essential thrombocythaemia following treatment with recombinant interferon-alpha (r-IFN-alpha). Prior to pregnancy, the first patient was treated for 10 months with r-IFN-alpha 3 x 10(6) units/d six times per week, and the platelet count ranged between 750 and 800 x 10(9)/l. Starting from the sixth week of gestation, the platelet count decreased to normal levels and remained so, resulting in a lower r-IFN-alpha requirement. Following successful delivery of a healthy newborn an abrupt rise of the platelet count to pre-gestation values was observed, necessitating increased r-IFN-alpha dosage before pregnancy. The second patient when she became pregnant had been treated with r-IFN-alpha 3 x 10(6) units/d six times per week for 10 weeks. Starting from the 24th week of gestation the platelet count decreased, and despite reduction in the dose of r-IFN-alpha reached normal values at the time of delivery. The exact mechanism for the platelet count normalization during pregnancy is unclear, and several possibilities are discussed.

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia.

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% CI 11.2-23.1 months) and a 2 year survival of 34.3 +/- 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% CI, lower limit 29.8 months) and a 2 year survival of 71.6 +/- 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 +/- 6.6% in the IDAC group and 67.3 +/- 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 +/- 10.8% versus 23.5 +/- 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 +/- 15.78 versus 44.4 +/- 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.

Hexasomy of chromosome 8 and trisomy of chromosome 11 characterize two karyotypically independent clones in a case of acute non-lymphocytic leukemia. Conventional cytogenetic and FISH investigation.

A case of ANLL following a myelodysplastic syndrome, probably resulting from occupational exposure to ionizing irradiation, with two cytogenetically unrelated clones, hexasomy 8 and trisomy 11, was investigated by conventional cytogenetics and FISH. Significant quantitative differences between data obtained by metaphase and interphase analysis of the hexasomy 8 clone were observed. A difference in the sensitivity to chemotherapy of the two clones was found: while the hexasomy 8 clone markedly decreased in response to treatment, the trisomy 11 clone remained unchanged.

Acute promyelocytic leukaemia with t(15;17) following treatment of Hodgkin's disease--a report of 4 cases.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is a recognized entity complicating successful therapy for Hodgkin's disease (HD) and other neoplasias after many years. This risk appears to be related to cumulative exposure to alkylating agents and procarbazine, while drugs affecting DNA--topoisomerase II, such as epipodophyllotoxins and anthracyclines, are also associated with t-AML developing after a much shorter latent period. PATIENTS AND METHODS: Of 56 patients with t-AML or myelodysplasia seen in our institutes during the period 1980-1994 we encountered 5 patients with acute promyelocytic leukemia (APL) all of whom had t(15;17). Four of these had been treated for HD with both chemotherapy and radiotherapy, and one with radiotherapy alone. RESULTS: To the best of our knowledge these appear to be the first cases of t-AML in HD with cytogenetically proven t(15;17). Similarly to other cases of t-APL reported after therapy for neoplasias other than HD, these patients also have a relatively favorable prognosis as seen in de-novo APL. CONCLUSIONS: Although rare, t-APL should be added to the list of late complications of therapy for HD.

A controlled trial of tranexamic acid therapy for the reduction of bleeding during treatment of acute myeloid leukemia.

In order to determine the efficacy of the antifibrinolytic agent tranexamic acid (TA) in reducing bleeding and platelet transfusions during the treatment of acute myeloid leukemia (AML), we conducted a randomized placebo-controlled double-blind study. Patients with AML undergoing induction or postremission consolidation chemotherapy were randomized into TA or placebo groups. Patients were not given platelet transfusions prophylactically but only when bleeding occurred. The severity of any bleeding event was scored. Thirty eight patients were randomized during induction. There were no significant differences between the two groups in the number of bleeding events and their severity or in the number of platelet transfusions given. Eighteen patients were studied during consolidation. In contrast, to the induction period, during consolidation there was a significantly less severe bleeding tendency in the TA group resulting in a lower platelet transfusion requirement [3.7 +/- 4.1 vs. 9.3 +/- 3.3 platelet units (p < .05)]. TA was well tolerated and no side effects were seen and no specific thromboembolic events were noticed. We conclude that giving TA during the thrombocytopenic period of AML patients undergoing consolidation chemotherapy is beneficial and safely reduces platelet transfusions.

Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride-rich lipoproteins.

Triglyceride rich-lipoproteins induce triglyceride accumulation in macrophages, leading to foam cell formation. The correlation between cell triglyceride accumulation and lipoprotein lipase (LPL) secretion in murine macrophages and the role that LPL plays in the accumulation process were examined. LPL secretion is defined as the extracellular LPL activity that accumulates during a 4-hour incubation of treated and untreated cells in a bovine serum albumin-containing RPMI-1640 medium. LPL secretion was suppressed (up to 70%) in a dose- and time-dependent manner when J774.1 cells were incubated with chylomicrons, very low density lipoproteins, and intermediate density lipoproteins but not with low or high density lipoproteins from normolipidemic and hypertriglyceridemic subjects. Oleic acid both suppressed LPL secretion and invoked triglyceride accumulation. Suppression of LPL secretion preceded gross triglyceride accumulation, was reversible, and was not the result of a reduction in LPL mRNA. P388D1 cells neither secreted LPL nor accumulated triglyceride. Inhibition of LPL secretion by tunicamycin in both peritoneal macrophages and J774.1 cells prevented a hypertriglyceridemic very low density lipoprotein-induced triglyceride accumulation, an effect that was counteracted by addition of exogenous LPL. The results suggest that 1) extracellular hydrolysis of lipoprotein triglyceride is a major factor in inducing foam cell formation and 2) LPL secretion may be regulated by cell energy needs, and when these needs are exceeded, LPL secretion is suppressed.