aclarubicin and Leukemia--Lymphoid

Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic. Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines. Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s. ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma. Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia. Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease. The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved. Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon. Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity. These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance; Heart; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Naphthacenes

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Age Factors; Aminoacridines; Amsacrine; Anthraquinones; Antibodies, Monoclonal; Azacitidine; Bone Marrow Transplantation; Child; Child, Preschool; Drug Administration Schedule; Etoposide; Humans; Ifosfamide; Immunotherapy; Infant; Interferons; Leukemia; Leukemia, Lymphoid; Liposomes; Middle Aged; Mitoxantrone; Naphthacenes; Prognosis; Teniposide; Transplantation, Homologous; Transplantation, Isogeneic; Vinblastine; Vindesine

An intensive 7-day combination chemotherapy protocol was designed to reinduce children with early bone marrow relapse of acute lymphoblastic leukemia (less than 6 months after the end of or during preceding treatment). This aggressive approach seemed to be justified for a group of patients who were at the highest risk for ultimate treatment failure. In all, 38 children were enrolled for study. The ratio of male (median age, 10 years) to female (median age, 13 years) subjects was 27:11. Thirty patients were treated for their first relapse and eight for their second or subsequent relapse. Isolated bone marrow involvement was present in 24 cases. All patients had received heavy pretreatment including anthracyclines with cumulative doses of between 120 and 240 mg/m2. 22 of these patients, achieved complete remission, ten did not respond to therapy, and six died from the toxicity of the protocol. Cardiac failure was the cause of death in one child (after additional radiotherapy for a mediastinal mass). No further clinical manifestation of cardiomyopathy could be observed. The other five patients died from hemorrhages or infectious complications. The main side effects were fever, gastrointestinal problems, stomatitis, and severe bone marrow aplasia lasting for about 2 weeks with nadirs of platelets and white blood count around days 10-14. The remission rate of 60% was acceptable, though not satisfactory. Only four children survived disease-free for 13+, 14+, 20+, and 22+ months after diagnosis of relapse.

Topics: Aclarubicin; Adolescent; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Trials as Topic; Cytarabine; Etoposide; Female; Germany, West; Humans; Leukemia, Lymphoid; Male; Naphthacenes; Prednisone; Remission Induction

Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic. Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines. Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s. ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma. Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia. Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease. The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved. Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon. Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity. These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance; Heart; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Naphthacenes

Topics: Aclarubicin; Daunorubicin; Doxorubicin; Flow Cytometry; Humans; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Tumor Cells, Cultured

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cerebellum; Cerebral Infarction; Female; Humans; Leukemia, Lymphoid; Middle Aged; Naphthacenes; Prednisolone; Remission Induction; Vincristine

In a phase I-II trial, 38 patients with acute myeloid leukemia (AML) were given single drug induction therapy with aclarubicin (ACM) according to two dosing schedules: treatment 1: 10 to 30 mg/m2/d to a maximum total dose of 300 mg/m2 or until development of unacceptable toxicity: treatment 2: 15 mg/m2/d in ten-day courses separated by ten-day intervals. Response rates were 15% with treatment 1 and 44% with treatment 2 (overall response rate 34%). Complete remission (CR) was achieved in 6 patients who had previously failed to respond to adriamycin (ADM). Toxicity was more frequent and more severe in those patients given more than 150 mg/m2 ACM per course. The main side effects were oropharyngeal mucositis and diarrhea. Three patients exhibited T wave inversion and one had an episode of auricular flutter. In a separate trial in 16 patients with AML we used cyclic chemotherapy combining ACM (20 mg/m2/d) and ARA-C (200 mg/m2/d) for seven consecutive days. Complete remission rate was 50%. Severe ventricular rhythm disorders were seen in two patients. In a phase I-II study, 19 patients with acute lymphoid leukemia (ALL) and 8 patients with non-Hodgkin lymphoma (NHL) were given ACM alone according to the regimen designated treatment 1 described above. Response rates were 11% (2/19) in ALL and 25% (2/8) in NHL. A review of the literature is presented in the discussion of the original trials reported herein.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Child; Child, Preschool; Cytarabine; Drug Evaluation; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Middle Aged; Naphthacenes

Aclarubicin, a new anthracycline antibiotic, was used to treat 24 adult patients with refractory adult leukemia, using a total dose of 300 mg/m2 (75 mg/m2/day X 4). There were 20 patients with acute myelogenous and four with acute lymphoblastic leukemia. Approximately two-thirds of the patients had a Karnofsky score of less than or equal to 2, and two-thirds had received two or more previous induction programs. Interim bone marrow evaluation was obtained in 18 of 30 remission induction courses and revealed marked hypocellularity in 14, inadequate specimens in three, and persistent disease in one. Seven patients received more than one course. Two patients refused further therapy. In patients with myelogenous leukemia, there were two complete remissions lasting 10 and 16 months and one partial remission lasting 4 1/2 months. There were no responders in patients with lymphoblastic leukemia. Toxicity included profound leukopenia and thrombocytopenia, moderate nausea and vomiting, diarrhea, and mucositis. There were no cardiac symptoms associated with the drug infusion, but there were three late events possibly associated with anthracycline cardiotoxicity. Used in this dosage schedule, aclarubicin is an active, but toxic, agent in the acute myelogenous leukemias.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes

Mitoxantrone, a new anthracenedione, was administered to thirty-nine patients with relapsed and refractory acute leukemia and to 12 patients with blastic crisis of chronic myelogenous leukemia between August 1981 and September 1984. Eleven patients were not evaluable and 40 were analysed. There were 24 males and 16 females with a median age of 37 yrs (range 6-73 yrs). Three of these were less than 15 yrs and 7 more than 60 yrs. The initial dose employed was 1.9 mg/m2/day X 5. Although eventually a starting dose of 12.3 mg/m2/day X 5 was used, about one half of cases were given more than 5 mg/m2/day X 5 by i.v. bolus. Among 25 patients with acute non-lymphocytic leukemia, there were 4 complete and 6 partial remissions. Among 7 patients with acute lymphocytic leukemia there was one complete remission and one partial remission. All patients except one who attained remissions had received prior anthracyclines. One of 8 patients with blastic crisis of chronic myelogenous leukemia had a partial remission. The durations of complete remission were 1, 1, 5+, 13+ and 17 weeks, respectively. Side-effects showed expected bone marrow depression. Mucositis occurred in ten patients. Gastrointestinal symptoms were noted in approximately 50%, but were mostly mild. Mild alopecia occurred occasionally. The trials were too short to allow evaluation of possible cardiac toxicity. These data indicate that mitoxantrone is non-toxic but hematological and a promising single drug for use in treating relapsed and refractory acute leukemia and suggest that further study would be worthwhile in order to identify its role in the first-line therapy of acute leukemia.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Blast Crisis; Child; Daunorubicin; Drug Evaluation; Drug Resistance; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Middle Aged; Mitoxantrone; Naphthacenes

A phase II study of mitoxantrone (Novantrone; dihydroxyanthracenedione) was conducted in 35 patients (22 male: 13 female) with acute leukemia. There were 35 evaluable cases with a mean age of 34 (range 8-61). Twenty-eight patients had acute non-lymphocytic leukemia (ANLL) and seven had acute lymphocytic leukemia (ALL). Mitoxantrone was administered intravenously 2-4 mg/m2 daily for five days and after the nadir a further 2-3 doses were added if necessary. All previously treated cases (22 patients) had been treated with anthracyclines; 13 had no previous treatment. Out of the 13 untreated cases there were six complete remissions (CRs) (46.2%) and five partial remissions (PRs) (38.5%), while out of 22 pretreated cases, four CRs (18.2%) and five PRs (22.7%) were obtained. In seven of the untreated cases the decrease of leukemic cells and neutrophil leukocytes were analysed. Mitoxantrone showed a longer duration of decrease and higher log decrease of leukemic cells in the bone marrow than daunorubicin or cytosine arabinoside. Seventy-three percent of patients showed gastrointestinal disturbances such as nausea or loss of appetite. In 38.1% SGPT elevation and in 8.8% abnormal ECG findings were observed. All side-effects were mild and reversible. From this data mitoxantrone seems a very promising agent in the treatment of acute leukemia and a phase III study is now being carried out.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Alanine Transaminase; Anthraquinones; Antineoplastic Agents; Child; Daunorubicin; Doxorubicin; Drug Evaluation; Drug Resistance; Electrocardiography; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukocyte Count; Male; Middle Aged; Mitoxantrone; Naphthacenes

Aclacinomycin A (ACM) is different from other anthracycline antibiotics in its antitumor activity and clinical effect. We report a case of acute promyelocytic leukemia complicated with severe esophageal ulcer by BH-AC . AMP therapy. The patient was 24 years old. In 1983, he achieved complete remission with BH-AC . DMP therapy but we confirmed relapse in April, 1984. ACM caused nausea, vomiting, diarrhea, alimentary tract bleeding and sore throat, together with a complication of esophageal stenosis. In about half of 10 cases receiving BH-AC . AMP therapy in our hospital, we noticed severe bleeding in the urinary treat, genital organs and alimentary tract. Care should therefore be taken with regard to mucosal injury when ACM therapy is used.

Topics: Aclarubicin; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Esophageal Stenosis; Esophagoscopy; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Naphthacenes; Prednisolone

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Naphthacenes; Prednisolone

21 patients with relapsing or primarily chemotherapy resistant acute myeloid or lymphocytic leukemia were treated with Aclacinomycin A (ACM). 25 mg/m2 ACM were given i.v. daily for 7 consecutive days. 17 out of 21 patients are evaluable, 2 with acute lymphocytic and 15 with acute myeloid leukemia. Two of the patients with acute myeloid leukemia entered complete remission. A further patient, primarily resistant to adriamycin and daunorubicin, experienced a partial remission. None of the patients with ALL responded to ACM.

Topics: Aclarubicin; Adolescent; Adult; Antibiotics, Antineoplastic; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes; Recurrence

A rapid decrease of myeloblasts and a remarkable increase of mature neutrophils, mostly with Pelger anomaly, were observed in the peripheral blood of a 51-year-old woman with terminal acute myeloblastic leukemia during 16 days of daily i.v. administration of 20 mg aclacinomycin-A (ACM-A). When the same dose was administered later on three consecutive days each week, a similar hematore neutrophils, mostly with Pelger anomaly, were observed in the peripheral blood of a 51-year-old woman with terminal acute myeloblastic leukemia during 16 days of daily i.v. administration of 20 mg aclacinomycin-A (ACM-A). When the same dose was administered later on three consecutive days each week, a similar hematore neutrophils, mostly with Pelger anomaly, were observed in the peripheral blood of a 51-year-old woman with terminal acute myeloblastic leukemia during 16 days of daily i.v. administration of 20 mg aclacinomycin-A (ACM-A). When the same dose was administered later on three consecutive days each week, a similar hematological change occurred again. An increase of myeloblasts observed between the third and the fifth week of this intermittent schedule was accompanied by that of mature neutrophils. Thrombopenia and anemia did not improve significantly. These findings may indicate the induction of leukemic myeloblasts by ACM-A into mature neutrophils. Administration of relatively small dose anthracyclines including ACM-A may be another potential choice in the treatment of refractory acute non-lymphocytic leukemia (ANLL) or ANLL after relapse.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Cell Differentiation; Female; Humans; Leukemia, Lymphoid; Middle Aged; Naphthacenes; Neutrophils

Aclacinomycin A (ACM) is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals than does doxorubicin. To define the effective dose for the treatment of patients with leukemia, we treated 43 patients with acute nonlymphoblastic leukemia (ANLL) or acute lymphoblastic leukemia (ALL) using ACM administered at three dose levels. All patients had previously received extensive treatment with other chemotherapy; their median cumulative dose of prior anthracycline was 340 mg/m2. An ACM dose of 100 mg/m2/day given for 2 days (total dose, 200 mg/m2) failed to produce significant bone marrow hypocellularity or remission in two patients. Total ACM doses of 300--360 mg/m2 (100 or 120 mg/m2/day x 3 days) produced marrow hypoplasia in 16 to 23 evaluable patients with ANLL. Overall, four of 32 patients with ANLL who received 300--360 mg/m2 of ACM achieved complete remission for duration of 1, 5+, 6 and 15+ months. Two of nine patients with ALL achieved partial remission. Toxic effects of this therapy included severe leukopenia and thrombocytopenia, nausea, mucositis, and diarrhea. ECG abnormalities were noted in 43% of patients who were carefully monitored; however, only one patient developed a significant decrease in left ventricular ejection fraction as measured by radionuclide cardiography. ACM produced only minimal alopecia and did not cause tissue necrosis following inadvertent subcutaneous infiltration. We conclude that 300--360 mg/m2 of ACM is an effective dose for the treatment of patients with ANLL and that further evaluation of this compound is indicated in patients who have received minimal prior therapy.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Heart Diseases; Humans; Leukemia; Leukemia, Lymphoid; Middle Aged; Naphthacenes; Neutropenia; Thrombocytopenia

Twelve patients with refractory acute leukemia (7 patients with acute myelocytic leukemia and 5 patients with acute lymphocytic leukemia) were treated with a new anthracycline antibiotic, aclacinomycin-A (ACM). ACM was administrated by intravenous drip infusion at a dose of 20 mg/day for 7 or 14 days and this was repeated after at least 7 days. Four of 12 patients (33.3%) achieved a complete remission; 3 of 7 acute myelocytic leukemia (42.8%) and 1 of 5 acute lymphocytic leukemia (20.0%). The days required for achieving the complete remission ranged from 23 to 78 days (median: 61) and the total doses of ACM used from 180 to 500 mg (median: 310), and the durations of complete remission from 11 to 28+ weeks (median: 21+). The untoward effects on digestive organs, such as nausea, vomiting and anorexia, and hematological toxicities were frequently seen; however, they were controlled by supportive treatment. Alopecia was not observed. Arrythmia was recognized in one patient at the initiation of ACM infusion with complete remission without withdrawal of ACM. These results suggest that ACM is a potentially effective anthracycline antibiotic in the clinical management of acute leukemia.

Topics: Aclarubicin; Adult; Aged; Female; Humans; Infusions, Parenteral; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Naphthacenes