Teruo Ino

We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75mg (1.25mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75mg (1.25mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

A 44 year-old woman with acute myeloid leukemia (AML, FAB, M4E) developed heart failure during treatment with anthracyclines for AML. She had not experienced heart disease and her left ventricular ejection fraction (LVEF) was 59% at the end of a successful remission induction therapy. Because her LVEF decreased to 33% after early consolidation therapy, the chemotherapy for AML was discontinued. The cumulative dose of daunorubicin, aclarubicin and mitoxantrone was 486 mg/m², 135 mg/m² and 55 mg/m², respectively. In October 1990, four months after the end of the chemotherapy, heart failure (class III, NYHA) developed and did not improve by treatment consisting of dobutamin, digoxin and diuretics. Anthracycline cardiomyopathy was histologically confirmed by endomyocardial biopsy. Then we administered selective β1-antagonist, metoprolol (Seloken^®), with an initial dose of 5 mg/day which was doubled 3 times every 4 or 8 weeks to 40 mg/day, according to the treatment schedule of dilated cardiomyopathy. She recuperated satisfactorily (Class I, NYHA), and was discharged on February '91. Her LVEF gradually improved and it has been maintained at above 50% on an outpatient basis. The patient has been in complete hematological remission during this period. It seems that low dose selective β1-antagonist therapy has a potential to improve myocardial function in some patients with anthracycline cardiomyopathy.