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In April, 1985, a 60-year-old Japanese male was diagnosed as having refractory anemia with an excess of blasts (RAEB). He thus was treated solely with blood transfusions until June, 1986, when a new diagnosis revealed that his illness had been transformed into acute myelogenous leukemia (M2). Chromosome analysis at the initial diagnosis had revealed a normal male karyotype. When the subsequent diagnosis of AML was made, however, a chromosomal abnormality [46, XY, -20, +der (20) t (?8;20) (q22;p13)] was detected. Myelodysplastic syndrome (MDS) in patients evidencing a karyotypic alteration from the initial karyotypic findings progresses in severity that includes overt leukemia, and results in a shorter survival than in patients who show no further karyotypic changes. Therefore, the prognosis of patients with MDS can be predicted more accurately by subsequently reanalyzing their chromosomes after the initial analysis, as well as by examining their peripheral blood/counts, and by monitoring bone marrow cytology.

A combination of cefmenoxime (CMX) and cefsulodin (CFS) which has a broad spectrum on various bacteria including Pseudomonas aeruginosa was evaluated for severe infections associated with hematological malignancies. Seventy one patients were treated with the combination therapy. Among them, 57 patients were evaluable for the effectiveness. Fourteen patients were not evaluable because 10 patients were subjected to additional therapy such as gamma-globulin, interferon, radiation and pulse therapy of a large dose of methylprednisolone, 3 were prophylactically treated and the remaining one was a patient with disseminated bone marrow metastasis of prostatic cancer and not a patient with a hematologic malignancy. Excellent responses were obtained in 24 (42.1%) patients and good response in 12 (21.1%) patients, with a total rate of effectiveness of 63.2%. Three patients who were treated prophylactically and one patient who suffered from prostatic cancer with metastasis to bone marrow, were included in the final evaluation of side effects. Side effects were observed in only one patient (1/61, 1.6%). Mild neutropenia was identified in a patient of 78 years of age in 4 days after the combined regimen was started. Neutropenia disappeared soon after the cessation of the treatment. These results showed that a combination of CMX and CFS was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

Ninety nine patients with leukemia and/or related disorders were treated with cefmenoxime (CMX). Among them, 77 patients had severe infections, while other 22 patients did not suffer from infection, but it was expected that they would fall into serious conditions if they were infected. Sixty of the 77 patients who had severe infection were used in the evaluation of effectiveness. The remaining 17 patients were not evaluated because they were subjected to combined treatments of CMX and other therapeutic agents such as other antibiotics, gamma-globulin or interferon. Excellent responses were found in 26 (43.3%) patients and good responses in 12 (20.0%) patients. In total, the rate of effectiveness was 63.3%. Nineteen of the 22 patients who were treated prophylactically with CMX were used in the evaluation of effectiveness, while 3 patients were excluded from the evaluation because peripheral neutrophils were counted to be more than 1,000/mm3 before CMX was administrated, although these 3 patients were used in the final evaluation to examine side effects. In the prophylactic treatment, the rate of effectiveness was 89.5%. The side effects were seen in 4 patients (4/82:4.9%). A different symptom was identified in each patient. These symptoms were skin rash, mild nausea, mild diarrhea and slight elevation of serum bilirubin. Prompt improvements of these symptoms occurred as soon as CMX administration was stopped. These results show that CMX is a therapeutically effective and safe antibiotics for the treatment of severe infections or for the prophylaxis of infections in patients associated with leukemia and/or related disorders.

A 68-year-old man with acute myelogenous leukemia (M2) was induced to complete remission by chemotherapy consisting of BH-AC and ACM-A on the 180th hospital day. Prior to therapy, chromosome analysis revealed 46, XY, del(5)(q22q33). No additional chromosome abnormalities were noted. Though 5q- was first associated with a preleukemic state, it is now known to be found in several different hematological disease. It has been suggested that patients with only a 5q- abnormality might have a better prognosis than those with a 5q- plus additional chromosome abnormalities. 5q- usually results from an interstitial deletion with break and fusion points at 5q11 or 12, 5q14 or 15, 5q22 and 5q33 or 35. The c-fms oncogene is located in the vicinity of band 5q34, so that a chromosome break at 5q33 or 34 may play an important role in the hematological disorders with 5q- chromosome abnormality.

We observed double minute chromosomes (dmin) and a homogeneously staining region (HSR) in the same metaphase cells obtained from a retinoblastoma cell line, Y79. All of the 132 metaphases examined contained an HSR on the short arm of chromosome 1(1pHSR) and five cells (3.8%) had two to four dmin. To determine whether 1pHSR and dmin carried amplified N-myc sequences, we performed an in situ hybridization using an N-myc probe. Silver grains clustered on and along the 1pHSR, but not on the dmin. These findings indicate that the HSR on chromosome 1 is associated with amplification of N-myc in Y79 cells.

Rearrangement of the breakpoint cluster region (bcr) and the chromosomal location of c-abl and 3'-bcr were studied in two patients with Philadelphia chromosome (Ph1)-negative chronic myelocytic leukemia (CML). One patient (patient 1) had a normal karyotype and the other (patient 2), 46,XY,inv(3)(q21q26). Both patients showed the bcr rearrangement by Southern blot analysis with a 1.2kb 3'-bcr probe. In situ hybridization studies demonstrated the location of the homologous sequences of bcr on chromosome 22 in patient 1, and on chromosomes 9 and 22 in patient 2. These findings indicate that the morphologically normal-looking chromosomes 9 and 22 in patient 2 are the result of a retranslocation between chromosomes 9q+ and 22q-, abnormalities which were first formed by a standard Ph1 translocation.

A 44-year-old Japanese male having refractory anemia with excess of blasts (RAEB) preceding acute myelomonocytic leukemia (AMMoL) with dysplastic marrow eosinophilia (M4Eo in the FAB classification) is reported. Sequential cytogenetic studies revealed a specific chromosomal abnormality, inv(16) (p13q22), when RAEB was first diagnosed and again when overt leukemic transformation compatible with M4Eo was manifested. However, during the interval between the RAEB and AMMoL, an unrelated abnormal karyotype without inv(16), 47,XY,+9, was seen, when hematological data revealed remission after a low dose of cytosine arabinoside was administered. In this patient eosinophils in the marrow were involved in the leukemic process cytogenetically, because a few metaphases overlaid with eosinophilic granules had the inv(16) with other numerical abnormalities.