aclarubicin and Leukemia--Monocytic--Acute

The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Cytarabine; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction

Aclarubicin, discovered by Umezawa in 1975, is a new cytostatic anthracycline antibiotic. It is one of the anthracyclines with the lowest cardiotoxicity, it is not mutagenic and it stimulates differentiation of tumour cells. The therapeutic index of aclarubicin (efficacy related to toxicity) is higher than that of doxorubicin and daunorubicin, using a proper dose schedule. Single dose therapy of aclarubicin shows only marginal efficacy, whereas multiple divided dose therapy exhibits efficacy comparable to that of doxorubicin and daunorubicin. Thus for clinical trials two dose schedules were designed: 25 mg/m2/day, days 1-7 for acute leukaemia; and 30 mg/m2/day, days 1-4 for solid tumours. Aclarubicin was shown to be highly active in acute leukaemia with 58% complete remissions in first relapse of AML. Good results were also seen in acute leukaemia in combination with cytosine arabinoside and thioguanine. In clinical trials with breast cancer and thyroid cancer the efficacy was in the same range as would be expected for doxorubicin, but side-effects were markedly reduced. Anorexia, mild nausea and infrequent vomiting were observed. Myelosuppression was common but dose reduction was not necessary. There was no alopecia and no congestive heart failure.

Topics: Aclarubicin; Animals; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colony-Forming Units Assay; Cytarabine; Daunorubicin; Doxorubicin; Humans; Leukemia L1210; Leukemia, Monocytic, Acute; Naphthacenes

We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia.

Topics: Aclarubicin; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 20; Combined Modality Therapy; Cytarabine; Disease Progression; Fatal Outcome; Female; Hemorrhage; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Monocytic, Acute; Mercaptopurine; Middle Aged; Neoplasm Proteins; Nuclear Pore Complex Proteins; Prednisolone; Sepsis; Translocation, Genetic

We have previously detected by immunofluorescent assay that the cellular localization of nucleophosmin/B23 (NPM) shifts from the nucleolus to the nucleoplasm (NPM-translocation) after exposure of cells to multiple agents. In order to improve the quantification of the NPM-translocation, we have developed a digital imaging technique. Human Lo leukemia cells, MCF-7 breast carcinoma cells, and fresh human leukemia cells were exposed to anthracyclines or actinomycin D for 4 h. The degree of NPM-translocation was determined and presented as the localization index (LI). Control cells had a LI of about 10, which indicates that the majority of NPM was localized in nucleoli. The LI for drug-treated cells decreased in a dosage- and time-dependent manner. The effect of two classes of anthracycline (daunomycin and aclacinomycin A) and different types of intercalators (daunomycin and actinomycin D) had additive effects on induction of NPM-translocation. The imaging procedure was easily applied to fresh leukemia cells, thus providing useful information regarding drug effects on cancer cells.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Nucleolus; Dactinomycin; Daunorubicin; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Humans; Image Processing, Computer-Assisted; Leukemia, Monocytic, Acute; Nuclear Proteins; Nucleophosmin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.

Topics: Aclarubicin; Aged; Antibiotics, Antineoplastic; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Naphthacenes

Topics: Aclarubicin; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Infusions, Intravenous; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Naphthacenes

Sixteen of 20 patients(80%) with adult ANLL treated with B H-AC X AMP therapy attained complete remission (CR). According to the FAB classification, CR rate was 6 out of 8 (75%) for M1, 3 out of 5 (60%) for M2, 2 out of 2 (100%) for M3, and 5 out of 5 (100%) for M4. The median of remission duration in 16 patients who attained CR was 8 months and appeared to be longer in patients with M2, rather than other types, of leukemia than in those with the other types of leukemia. BH-AC X AMP therapy is highly effective for remission induction in adult ANLL and long term disease free survival could be expected by addition of appropriate maintenance therapy.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

A comparative trial of a combination of daunorubicin and cytosine arabinoside (Regimen A) and a combination of aclarubicin and cytosine arabinoside (Regimen B) was performed. Sixteen patients with acute non-lymphocytic leukemia, previously untreated, were entered into this study. Five of 8 patients (62.5%) obtained a complete remission (CR) in Regimen A and B, respectively. The days required for achieving a CR varied from 37 to 46 days in Regimen A and from 22 to 56 days in Regimen B. The total doses of daunorubicin and cytosine arabinoside were from 100 to 240 mg and from 640 to 1,120 mg in Regimen A, respectively. Those of aclarubicin were from 180 to 300 mg and from 660 to 1,000 mg in cytosine arabinoside in Regimen B. In a comparative study on hematological changes, toxic effects on peripheral white blood cell, platelet and nucleated cell counts in bone marrow tended to appear later in Regimen B compared to those in Regimen A. Side effects on digestive system such as nausea and vomiting and vascular pain were more frequently recognized in patients treated with Regimen B, although they were managed by symptomatic treatment. The results indicated the usefullness of aclarubicin in combination chemotherapy for the treatment of acute non-lymphocytic leukemia.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes; Random Allocation

Topics: Aclarubicin; Adult; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone