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In order to characterize clinical and biological characteristics of elderly patients with acute myelogenous leukemia (AML), we retrospectively analysed 83 elderly patients aged 60 years or more and, as a control, 114 younger patients aged 15 to 59 years who were admitted to our hospital between August 1984 and January 1998. There was a significantly higher incidence of preceding myelodysplastic syndromes in the elderly patients. They also had a significantly higher incidence of unfavorable cytogenetic abnormalities (loss or partial deletion of chromosome 5 or 7) and a significantly lower incidence of favorable cytogenetic abnormalities, such as t(15:17), t(8:21), or inv(16). With regard to FAB subtypes in de novo AML, the incidence of M3 subtype was significantly lower in the elderly group. Myeloperoxidase positivity of AML cells in the elderly group was lower than that in the younger group. Laboratory data at presentation disclosed a lower peripheral leukemic cell count, a higher fibrinogen level, a lower serum protein level, and a higher serum creatinine level in the elderly group. They also had poorer performance status and more frequent concomitant diseases at presentation, including liver diseases, heart diseases, or documented infections. It was concluded that elderly AML patients 60 years or older had a higher incidence of poor prognostic factors compared to younger patients.

We retrospectively analyzed treatments and outcomes for 83 acute myelogenous leukemia (AML) patients aged 60 years or more (median age 71) admitted to our hospital between August 1984 and January 1998. Complete remission was achieved in 36% of 78 patients who received anti-leukemic therapy, and median overall survival was 227 days. In addition to abnormal karyotypes involving chromosome 5 or 7, administration of less than 120 mg/m2/course of daunorubicin (DNR) during the initial treatment phase was an unfavorable prognostic factor for both CR and survival. Only 41% of all patients received 120 mg/m2/course of DNR or more, and had a significantly higher CR rate (56%) and longer survival, with a median of 389 days. It was suggested that intensive chemotherapy was effective for selected elderly AML patients who were relatively younger and had good performance status, although the number of such patients was limited in our study.

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 75 mg (1.25 mg/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.

In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.

Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families were described. All cases were clinically manifested by jaundice and splenomegaly. Hemolysis was evident from indirect hyperbilrubinemia, reticulocytosis and decrement of serum haptoglobin. Red blood cells showed morphological abnormalities such as poikylocytosis, anisocytosis and target cells on blood smears. Both direct and indirect Coombs' tests were negative. Ham test, sugar water test and hemoglobin electrophoresis showed no abnormalities. Osmotic fragility test showed decreased membrane fragility. Lipid analysis of red cell membrane showed increment of phosphatidylcholine content and decrement of sphingomyelin content, although plasma lipids were essentially normal. Influx and efflux of sodium through the red cell membrane were both increased. Splenectomy was performed without effect on one patient and the mother of other patients.

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 beta 1-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 beta 1-antagonist therapy has a potential to improve myocardial function in some patients with anthracycline cardiomyopathy.

Seventeen patients with refractory or relapsed, intermediate or high grade non-Hodgkin's lymphoma (NHL) were treated with the combination of dexamethasone (40 mg/body x 3d, iv) (DeVIC) between January and December 1992. The treatments were repeated every three weeks for a minimum of two courses unless the patient had PD. G-CSF (2 micrograms/kg, sc) was given during leukopenia in most cases. Of 16 evaluable patients 6 (38%) achieved a complete remission (CR) and 4 showed a partial remission. With median follow up of 15 (7-26) months (mos.) all CR patients were alive in CR, except for 1 patient who died of secondary AML. The actuarial 50% survival duration after DeVIC was 15+ mos. One patient died of sepsis but myelosuppression was generally moderate and no other serious toxicity was observed. Although this is a preliminary study, DeVIC regimen seems to be an effective salvage therapy for patients with refractory or relapsed NHL with acceptable toxicity.

We analyzed immunoglobulin (Ig) gene rearrangements in 69 patients with B-cell malignancies by Southern hybridization. We used 5 probes which covered JH 5'S mu and S gamma 3 loci of the Ig heavy (IgH) chain gene, and C kappa and kappa de loci of the Ig light (IgL) chain kappa gene, respectively. DNA rearrangements were observed in 68 out of the 69 patients using the JH probe. In 97% (33/34) of patients with non-Hodgkin's lymphoma (NHL), 100% (5/5) of chronic lymphocytic leukemia (CLL), 42% (10/24) of non-T cell acute lymphoblastic leukemia (non-T ALL), and in 0% (0/4) of chronic myelogenous leukemia lymphoid crisis (CML-LBC), the rearrangements were detected by C kappa and/or kappa de probes. Furthermore, the genotype of the light chain was defined by rearrangement patterns of these 2 probes. The by using the 5'S mu-probe, class switch recombinations were detected in 76% (25/33) of NHL, 20% (1/5) of CLL, 17% (4/24) of non-T ALL, and in 0% (0/4) of CML-LBC. Among them, 1 case of IgM NHL and 3 cases of double bearer NHL had rearranged on both IgH alleles by the constant region. The results of this study indicate that genotypes correspond well to phenotypes of B-cell malignancies and that the determination of genotype will be useful for making an exact diagnosis of B-cell malignancies.

A 40-year-old female was admitted in August 1989 with a diagnosis of acute promyelocytic leukemia (AML; M3). One course of modified-DCMP regimen induced complete remission in September, but she developed spiking fever at a nadir period of WBC after induction chemotherapy. CT revealed multiple hepato-splenic abscesses presumably due to candida infection. She was treated with intravenous administration of amphotericin B (AMPH-B) and other antifungal agents. Despite the hematological remission and prolonged use of these antifungal agents, high fever persisted. A catheter was inserted into the portal vein under ultrasonic-guidance. AMPH-B was administered through the catheter: the initial dose was 3 mg/day and was soon increased to 20 mg/day. Her fever subsided in 1 week, and the sizes of liver abscesses on CT reduced markedly. Chill and hypokalemia were observed during this therapy. The catheter was removed from the portal vein after 29 days. Partial portal vein thrombosis was noted around the catheter tip. This case suggests the usefulness of intraportal administration of AMPH-B in patients with hematological malignancy developing multiple liver abscesses.

We analysed immunoglobulin (Ig) gene rearrangements in 28 patients with multiple myeloma by Southern hybridization method. We used 5 probes which cover C kappa and kappa de loci of Ig light chain kappa gene, and JH, 5'S mu and S gamma 3 loci of Ig heavy chain gene. In 11 out of 12 patients with kappa-producing myeloma, DNA rearrangements were observed using C kappa probe. Among them, kappa de region was rearranged in 7 patients and kept germline configuration in 4 patients. In all of 14 patients with lambda-producing myeloma, C kappa region was deleted and kappa de region was rearranged. 5'S mu-probe was very useful for detecting class switch recombination, and furthermore by using S gamma-probe together, S mu-S gamma joining could be detected. In all of 10 patients with gamma-producing myeloma, 5'S mu and S gamma-probes detected the rearranged band of the same size on at least 1 allele, which suggested the presence of S mu-S gamma joinings. In 8 of 10 patients with Bence-Jones myeloma, 5'S mu-probe detected rearranged bands and the presence of class switch recombinations were suggested as observed in other Ig secretory myelomas. In other 2 patients with Bence-Jones myeloma, non-functional class switch recombinations were detected. The results of this study indicated that genotypes corresponded well to phenotypes in multiple myeloma, and further analysis in other types of B cell malignancies will be interesting.

Clinicopathologic analyses were performed on 11 patients with histopathologic diagnosis of Hodgkin's disease which was confirmed immunohistochemically with the use of anti-Leu M 1 which is known to be specific to Reed-Sternberg cells. Patients with clinical stage II developed infradiaphragmatic involvement after Mantle field irradiation and should have been treated with extended field irradiation or combined modality therapy because of the possibility of PSIII1. Maintenance VENP therapy seemed to sustain remission but may have caused opportunistic infections. There were no rearrangements in either immunoglobulin or T cell receptor genes studied in two patients.