[Multiple discriminant analysis for prognosis of refractory anemia].

Forty-eight patients with refractory anemia (RA) were retrospectively analyzed for their prognosis and subclassified into three groups: 12 patients with hematological improvement (A), 23 patients with no changes (B), and 13 patients with progression to RAEB or acute leukemia (C). For all patients, the median survival were 49.2 months, and the rate of leukemic transformation was 16%. The median survivals were 60.6, 32.1, and 17.9 months, respectively, for groups A, B and C. The factors indicating poor prognosis were low reticulocyte counts, low neutrophil alkaline phosphatase activity, low% red cell utilization, high M/E ratio, high blast percentage in the bone marrow and cytological abnormalities in the granulocyte and megakaryocyte series. By using multiple discriminant analysis, we obtained a formula for the prognostic estimation with a discrimination probability of 62.5%. This formula could predict either the patients with good (Y greater than 0.85) or poor (Y less than 0.59) prognosis, and might be useful to select the treatment for this intractable anemia at the time of diagnosis.

Androgen in the treatment of refractory anemia.

We retrospectively evaluated the efficacy of androgen in the treatment of refractory anemia (RA) and compared patient characteristics and the probability of survival in androgen-responder and nonresponder groups. Forty patients with RA were treated in our hospital between 1975-1989, and 27 were treated with various derivatives of androgen. Eleven of the latter responded effectively to androgen therapy, representing an efficacy rate of 40.7%, higher than that of any other treatments thus far reported. The probability of 10-year survival estimated by the Kaplan-Meier method was 75.0% for the responder group and 41.3% for nonresponders, with a median follow-up of 1202 and 1272 days, respectively. In addition, the percent probability of transformation-free survival was higher among androgen-responders than among nonresponders, though the difference was not significant. Transformation from RA to RAEB or overt leukemia was seen in only one case among the former group, but in six among the latter. With respect to patient characteristics, only the percentage of marrow myeloblasts differed significantly between the groups.

Human G-CSF produced by adherent cells in the presence of human recombinant GM-CSF.

Adherent cells (AdCs) in blood from normal volunteers produced granulocyte-macrophage (GM) colony-stimulating activity (CSA) in the presence of 10 ng/ml of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in vitro. GM-CSA produced by adherent cells in the presence of GM-CSF reached a plateau level on day 6. Colonies stimulated by adherent cell-conditioned medium (AdC-CM-GM-CSF), which had been harvested after 6 days of incubation of AdCs with rhGM-CSF, were granulocyte predominant. When phagocyte-depleted marrow mononuclear cells (PD-M-MNCs) were cultured with AdC-CM-GM-CSF and anti-rabbit serum against rhGM-CSF, 99% of the colonies on day 7 were exclusively composed of neutrophils. When 2 X 10(4) PD-M-MNCs were cultured in a medium containing AdC-CM-GM-CSF, AdC-CM-GM-CSF + anti-GM-CSF, AdC-CM-GM-CSF + anti-G-CSF, or AdC-CM-GM-CSF + both of the anti-bodies, the PD-M-MNCs formed (mean +/- SD) 100 +/- 2.0%, 64.3 +/- 2.5%, 38.6 +/- 0.4%, and 6.0 +/- 0.4% GM colonies, respectively. Furthermore, northern blot analysis revealed that AdCs incubated with 10 ng/ml of rhGM-CSF for 6 h expressed much more mRNA of G-CSF than those without the CSF. These data indicated that AdCs in blood produce G-CSF in the presence of GM-CSF.

[Mixed blast crisis with the cytogenetic evidence of three clonal evolutions].

A 46-year-old man was diagnosed as having chronic myelogenous leukemia (CML) in chronic phase in Dec. 1985. In Dec. 1987, anemia and leukocytopenia progressed, and the percentage of blast cells increased in the bone marrow. The blast cells were lymphoblastoid and positive for TdT. It was treated as a lymphoid crisis with vincristine and prednisolone, and complete remission was achieved. However, the blasts (11%) were observed in the bone marrow in Mar. 1988, and the chromosomal analysis revealed 46, XY, t (2q-; 11q+), t (9q+; 22q-) in 13 out of 20 cells. In June, the percentage of the blasts increased again, but chromosomal analysis showed a different karyotype, 46, XY, t(2p-; 11p+), t(9q+; 22q-) which was observed in 9 out of 10 cells. Then, myeloblastoid cells increased rapidly in spite of the chemotherapy in Dec. 1988. The chromosomal analysis showed 46, XY, 2p-, 7q-, 9q+, 11p+, 22q- in all analyzed cells. The rearrangement of the bcr gene could be detected by the Southern blotting. The blasts were positive for CD7, CD11, CD13, CD33, CD36, CD41 and CD42, suggesting that the blasts had the surface phenotypes of both myeloid and megakaryocytoid-lineage. This is a case with the mixed blast crisis that changed from the lymphoid to the myelo-megakaryocytoid in nature, in which three clonal evolutions were observed during the clinical course.

[Multivariate analysis of acute leukemia].

The outcome of chemotherapy in patients of 150 cases of acute leukemia was investigated. Patients were divided into two groups, that is group I: 100 cases of acute leukemia treated between 1980-1984, group II: 50 cases of acute leukemia between 1985-1986. Complete remission was achieved in 66% of group I and in 82% of group II. Using multivariate analysis, the initial levels of FDP and WBC count and age were found to be important factors to induce complete remission. Female sex was suggestive of a longer remission duration and survival by discrimination analysis.