Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia).

Superoxide anion (O2-) production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL) was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6) neutrophils, p less than 0.05). In 10 patients with myelodysplastic syndrome (MDS), however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01), but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.</p

Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.</p

Treatment of relapsed acute myelocytic leukemia with a combination of aclarubicin and cytosine arabinoside.

Relapses in nine patients with acute myelocytic leukemia were treated with a combination of aclarubicin (ACR) and cytosine arabinoside (ara-C). ACR, 40 mg/m2/day, was administered daily by intravenous injection from day 1 to day 3 and ara-C, 60-80 mg/m2/day, divided into 2 doses, was given every 12 h by intravenous infusion from day 1 to day 7. Depending on the state of the bone marrow, ACR-ara-C regimen was modified in administration period and repeated after the resting periods of at least 7 days. Complete remission was obtained in 7 of 9 patients (77.8%). The time required for achieving the complete remission varied from 20 to 55 days with a median of 39 days. The duration of complete remission was from 8 to 52 weeks with a median of 22 weeks. Side effects on digestive system such as nausea, vomiting and anorexia, were seen in all patients, although they were managed by symptomatic treatment. The results indicate the effectiveness of this ACR-ara-C regimen in the clinical management of acute nonlymphocytic leukemia.</p

Experimentail studies on the prevention of myelosuppression during cancer chemotherapy Part I : Accelerated recovery from cyclophosphamide induced myelosuppression by administration of Bestatin, 3-(R)-amino-2-(S)-hydroxy-4-phenylbutanoyl-(S)-leucine, in mice

The hemopoietic potential of Bestatin, a new immunomodulator prepared from the culture medium of Streptomyces olivoreticuli, was studied concerning its effects on the recovery from cyclophosphamide(CPA)-induced myelosuppression and on autologous CFUs in irradiated mice. In mice treated with CPA (300 mg/kg, i.p., day 0), the recovery from granulocytopenia and myelosuppression was significantly accelerated by administration of Bestatin (0.05 mg/kg, i.p., -day 5 to -day 1). Bestatin, administrated i.p. at a dose of 0.05 mg/kg on -day 1, increased the number of autologous CFUs in irradiated mice, indicating that Bestatin acted at the level of multipotent stem cells. These result indicate that Bestatin may be useful in the clinical management of myelosuppression induced not only by cancer chemotherapy but also by radiation therapy

Experimental studies on the prevention of myelosuppression during cancer chemotherapy Part II. Comparative sudies on the hemopoietic potentials of immunomodulators, Bestatin, streptococcal preparation OK-432 and Carboxyethylgermanium Sesquioxide (Ge-132), in mice

The hemopoietic potentials of three immunomodulators, Bestatin, OK-432 and Ge-132, were compared in terms of the effects of the drugs on the recovery from cyclophosphamide (CPA)-induced myelosuppression, and on autologous CFUs in irradiated mice. The recovery from CPA-induced myelosuppression was significantly accelerated in mice pretreated with Bestatin or OK-432 as compared to mice pretreated with Ge-132 or physiological saline. The effect of OK-432 was somewhat superior to that of Bestatin, but there were no significant differences in the days to nadir and in the days required for the recovery from nadir. Both Bestatin and OK-432 significantly increased the number of autologous CFUs in irradiated mice as compared to Ge-132 and Lentinan. Most chemotherapeutic schedules are divided into four therapeutic phases : induction, consolidation, maintenance and intensification. The last two phases were usually applied to outpatients ; therefore, hemopoietic agents, such as Bestatin, which can be orally administrated, may be useful clinically for the prevention of chronic myelosuppression during maintenance and intensification chemotherapy