zinostatin and Leukemia--Myeloid--Acute

A 15-year-old girl was diagnosed as having acute nonlymphocytic leukemia (ANLL, FAB M2) in January 1990 and achieved complete remission with chemotherapy. She was readmitted to our hospital with a hearing disturbance and hoarseness in October 1990. A suprapharyngeal tumor was found on cranial MRI, and bone marrow leukemic cells were slightly increased in number. Involvement of leukemic cells was proven by biopsy of the tumor. Therefore, we made a diagnosis of ANLL relapse with Garcin's syndrome. To our knowledge, this is the first reported case of leukemia complicated by Garcin's syndrome.

Topics: Adolescent; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cranial Nerve Neoplasms; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Paralysis; Prednisolone; Recurrence; Syndrome; Zinostatin

A 23-year-old male who had suffered recurrent relapses of acute myelocytic leukemia was treated with a protocol including neocarzinostatin (NCS) and complete remission was obtained. At the age of 11 years, he had complained of general fatigue and anemia, and was diagnosed as having AML because of the presence of leukemic cell infiltration in the bone marrow as well as peripheral blood. Auer bodies and a positive reaction to peroxidase were found. The last episode of relapse occurred at the age of 15 years, when he achieved complete remission following a trial protocol which included NCS. NCS seemed to be effective after it had been used intravenously for a short time. The patient has maintained complete remission for the past 7 years and has had no consolidation therapy in the last 3 years. For the last 18 months, he has been working in a market as a clerk 8 hours a day. NCS with a rapid infusion time seems to have effects on leukemic cells when it used with proteolytic enzyme. Neither skull radiation nor testicular biopsy were attempted. Results of CSF examination were within normal limits, but EEG and CT scan revealed the probability of early-stage leukoencephalopathy, although no significant clinical signs were observed. He had suffered an asthmatic attack before the onset of AML, but no further attack occurred until several months ago. In order to establish any relationship between these two diseases, further detailed analysis will be necessary.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid, Acute; Male; Prognosis; Recurrence; Remission Induction; Zinostatin

An analysis of prognostic factors was performed on a series of 50 adult patients with acute leukemia, treated in our department in the Tokai university Hospital between July, 1975 and June, 1980. The diagnosis was made in all cases on the basis of May-Grünwald-Giemsa-stained smears of peripheral blood and bone marrow. The patients were treated with two successive protocols. One course of induction chemotherapy consisted of 40 units/kg/day of neocarzinostatin, 1.2-1.6 mg/kg/day of cytosine arabinoside, 0.6-0.8 mg/kg/day of daunorubicin and 0.8-1.6 mg/kg/day of prednisolone on days 1-4 for acute nonlymphocytic leukemia, and the other consisted of 0.04 mg/kg/day of vincristine on day 1, 0.6-0.8 mg/kg/day of daunorubicin on days 1-4, 0.8-1.6 mg/kg/day of prednisolone on days 1-4 for acute lymphocytic leukemia. Consolidation and intensification therapies were given every 1-2 months after complete remission, and the protocols were basically the same as those of the induction therapy. Maintenance therapy consisted of 1.2-1.6 mg/kg/day of cytosine arabinoside, twice a week or 2 mg/kg/day of 6 MP orally. Risk factor leading to poor prognosis of acute leukemia were considered to be (1) advanced age (older than 50 years, P less than 0.05), (2) M5 (monocytic leukemia), (3) thrombocytopenia (less than 50,000 cmm-1), and (4) chromosome abnormalities of blast cells.

Topics: Acute Disease; Adolescent; Adult; Aged; Chromosome Aberrations; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Prednisolone; Prognosis; Vincristine; Zinostatin

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Prednisolone; Zinostatin

A technique was developed for continuous iv infusion chemotherapy in an inbred rat model of acute myelogenous leukemia. Polyethylene tubing was inserted surgically into the internal jugular vein of adult WF rats, burrowed sc to the base of the tail, and connected to an infusion pump. A flexible spring was sutured at the base of the tail and fastened to the cage wall; it protected the infusion catheter and allowed movement of the rat within the cage. This technique was used to compare bolus with continuous infusion therapy with adriamycin, cytosine arabinoside, and neocarzinostatin. Only small differences were noted in host toxicity and in antitumor effect against tumor grown as a subcutaneous myeloblastoma. Nearly three times more neocarzinostatin was required by continuous infusion for an effect equivalent to that of bolus injection. In contrast, continuous infusion of methotrexate with concurrent thymidine infusion prevented toxicity, enhanced the antitumor effect, and prolonged survival. This infusion system should facilitate rapid preclinical evaluation of drugs considered for constant iv infusion therapy.

Topics: Animals; Antineoplastic Agents; Cytarabine; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Infusions, Parenteral; Injections, Intravenous; Leukemia, Experimental; Leukemia, Myeloid, Acute; Rats; Rats, Inbred WF; Thymidine; Zinostatin

Neocarzinostatin, an antineoplastic agent which is effective against human leukemia, induced unscheduled DNA synthesis in human leukemic leucocytes. This indicated the existence of repair process against at least a part of DNA damage caused by the agent. The extent of unscheduled DNA synthesis increased in parallel with the concentration of Neocarzinostatin up to 5 microgram/ml, followed by a decline at more than 5 microgram/ml. Leucocytes from patients with chronic myelogenous leukemia had higher repair synthesis after Neocarzinostatin treatment compared to those from patients with acute leukemia. The amount of repair synthesis correlated well with the proportion of immature leucocytes among chronic myelogenous leukemia samples, but such correlation was not found among acute leukemia samples.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; DNA Repair; Dose-Response Relationship, Drug; Female; Humans; Hydroxyurea; In Vitro Techniques; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; Zinostatin

Neocarzinostatin (NCZ), an acidic polypeptide antibiotic, was given to 47 patients with cancer and leukemia, and tolerance to two schedules, a single dose given as a 2 hour infusion and a continuous infusion over 5 days was investigated. Immediate reactions, including fever, chills, rigor, hypertension and mental confusion, were dose-limiting for the 2 hour infusion schedule, occurring at 3000 U/m2 and higher. Continuous administration for 5 days eliminated the immediate reactions and then hematological toxicity--often prolonged leukopenia and thrombocytopenia--became dose-limiting. Other toxicities of NCZ at both dose schedules included anemia, fever and chills, anorexia, nausea and vomiting, hepatic dysfunction, azotemia, hypophosphatemia, aminoaciduria, stomatitis, phlebitis and/or cellulitis at the venous infusion site and pruritus. Patients with solid tumors who had received little or no prior chemotherapy and had good bone marrow reserve tolerated up to 6000 U/m2/24 hours X 5 days. One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Bone Marrow; Child; Drug Administration Schedule; Drug Evaluation; Drug Tolerance; Female; Fever; Humans; Hyperbilirubinemia; Infusions, Parenteral; Leukemia; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasms; Remission, Spontaneous; Uremia; Zinostatin

Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Bone Marrow; Child; Child, Preschool; Drug Evaluation; Drug Hypersensitivity; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Neoplasms; Remission, Spontaneous; Shivering; Vomiting; Zinostatin

A typical case of smoldering acute leukemia has been followed up for long-standing course. This 73 year-old woman survived 3 years and 9 months after diagnosis of acute myelogenous leukemia. The hematological study on admission showed hypoplastic bone marrow with 51.6% of abnormal myeloblasts, although a few myeloblasts were seen in the peripheral blood. Intensive anti-leukemia chemotherapy was withheld during the whole course except on the terminal acute phase. Three episodes of pneumonia occurred and then, the proliferation of leukemic cells subsided concomitnantly after the exacerbation of infection. The direct and/or host-mediated anti-tumor effect by infectious organism was suggestive in this case. The labeling index with 3H-TdR of leukemic cells was 4.9%, suggesting the slow multiplication. Positive tuberculin reactivity and normal ratio of lymphocyte blastogenesis confirmed the preserved cellular immunity. These factors might be considered to be closely related with the smoldering course of this particular case.

Topics: Aged; Bone Marrow; Bone Marrow Cells; Female; Humans; Leukemia, Myeloid, Acute; Pneumonia; Prognosis; Zinostatin

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission, Spontaneous; Zinostatin

Topics: Adolescent; Adult; Cytarabine; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Prednisolone; Statistics as Topic; Vincristine; Zinostatin