Hiromi Yashige

Detection of karyotypic abnormalities in most patients with acute nonlymphocytic leukemia by adding ethidium bromide to short-term cultures

A modified short-term culture method, in which cultured bone marrow cells were treated with ethidium bromide to prevent chromosome condensation was used to study the chromosomes of 70 patients with acute nonlymphocytic leukemia. Clonal karyotypic abnormalities were detected in 60 patients. Among these, 35 patients showed one of recurrent type specific alterations. A close relationship between karyotypes and clinical outcome was shown: thus, t(8;21) or a single miscellaneous chromosomal defect associated with a favourable prognosis whereas t(9;11) or a complex karyotype related to a poor prognosis. The ten cytogenetically normal patients did not appear to have a favourable prognosis.

Bilineage response in refractory aplastic anemia patients following long-term administration of recombinant human granulocyte colony-stimulating factor

Abstract: 5 patients with refractory aplastic anemia (AA) received long‐term administration (2–11 + months) of recombinant human G‐CSF (rhG‐CSF) in doses from 250–500 μg/body/day by intravenous infusion or 75–300 μg/body/d by subcutaneous injection. All 5 evaluable patients showed a substantial increase in absolute neutrophil count (ANC) with a recovery of myeloid components in the bone marrow after 1 to 2 months of treatment. Interestingly, 2 out of the 5 patients showed a dramatic improvement in severe anemia after 2 to 4 months of treatment accompanying a recovery of erythroid components in the bone marrow. In addition, there was no serious infection before or during therapy. Long‐term administration of rhG‐CSF was well tolerated because of its minimal toxicity. Clonal assay revealed a recovery of myeloid progenitors in all patients and a recovery of erythroid progenitors in 3 out of the 5 patients. These results suggest that long‐term administration of rhG‐CSF at least mobilizes residual myeloid as well as erythroid progenitor cells and induces a bilineage response in severe refractory AA.

Micronuclei and nuclear abnormalities observed in erythroblasts in myelodysplastic syndromes and in de novo acute leukemia after treatment.

The frequencies of erythroblasts with micronuclei (EBM) and erythroblasts with aberrant nuclear shapes (EBAN) in bone marrow were evaluated in 60 patients with untreated myelodysplastic syndrome (MDS), and also in 21 patients with acute leukemia before and after treatment, and the results were compared regarding cytogenetic patterns. In patients with acute leukemia, the frequencies of EBM and EBAN in bone marrow were 0.60 ± 0.35% (mean ± SD) and 1.2 ± 1.1% before treatment, respectively, the former of which was higher than those obtained from 93 patients with various nonmalignant diseases (p < 0.01). After treatment with antileukemic drugs, the mean values of them significantly increased 9.7 and 6.1 times from the pretreatment ones, respectively. No correlation was found between the yields of EBM and EBAN and cytogenetic patterns, although regimens including administration of vincristine seemed to cause them more frequently. Most patients with MDS showed a consistent increase of EBM and EBAN at the time of diagnosis irrespective of the treatment; the mean frequencies were 7.7 and 6.3 times higher than those obtained from patients with nonmalignant diseases, respectively. Furthermore, the numbers of EBM and EBAN were significantly higher in patients with an abnormal karyotype than those with a normal karyotype (p < 0.05 for EBM and p < 0.001 for EBAN). In particular, 8 patients with a monosomy 7q showed a marked increase of EBAN (4.7 ± 4.4%) and EBAN (13 ± 6.5%). These findings revealed that drastic changes in the morphology of erythroblasts were characteristic features of MDS, and may reflect a disturbance in kinetochore/spindle microtubules, such as endoreduplication, c-mitosis or restitution, in addition to chromosome lagging.

Translocations t(15;17) and t(9;14)(q34;q22) in a case of acute promyelocytic leukemia with increased number of basophils

A patient with a variant form of acute promyelocytic leukemia (M3 variant) associated with an increased number of basophils was found to present a reciprocal translocation, t(9;14)(q34;q22) in addition to t(15;17)(q22;q12). Although several cases of acute nonlymphocytic leukemia with increased bone marrow and peripheral blood basophils have been reported, this is the first case in which both the t(9;14) and basophilia were observed in a patient with M3. Our findings support the hypothesis that 9q34 may be associated with the chromosomal location of genes regulating the production and maturation of basophils.

Treatment of Idiopathic Neutropenia in the Elderly with Recombinant Human Granulocyte Colony-Stimulating Factor

We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) intravenously for 2 weeks to 2 elderly patients with severe neutropenia. The absolute neutrophil count (ANC) recovered promptly after the initiation of rhG-CSF therapy and reached a peak (greater than 10 x 10(9)/l) on the 13th day. The ANC fell rapidly after rhG-CSF was discontinued, but it remained within the normal range after therapy. There were no side effects during the entire course of treatment. Therefore, rhG-CSF seems to be a most beneficial treatment in elderly patients with severe neutropenia.