thioguanine-anhydrous and Hemorrhage

A high hemorrhagic risk and a complete response to the differentiative agent all-trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Cytarabine; Cytoplasmic Granules; Disease-Free Survival; Disseminated Intravascular Coagulation; Doxorubicin; Female; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Life Tables; Male; Middle Aged; Prospective Studies; Remission Induction; Survival Analysis; Thioguanine; Treatment Outcome

Fifty-seven adult patients with acute promyelocytic leukemia (APL) were treated between 1974 and 1984 with daunorubicin (DNR) or 4-(9-acridinylamino)methanesulfan-m-anisidide (AMSA) in combination with arabinosylcytosine (Ara-C) and 6-thioguanine (TG); they also received prophylactic heparin. Forty-one patients (72%) achieved complete remission (CR), including 11 of 12 patients who received the AMSA-containing regimen. The incidence of early fatal hemorrhage was 14%, lower than that of earlier studies or other published reports. Elevated WBC and serum lactate dehydrogenase levels at diagnosis were associated with an increased incidence of life-threatening hemorrhage and shorter remission duration. Advanced age was an unfavorable prognostic factor for male patients. Both DNR and AMSA in combination protocols are effective treatments for APL. The incidence of CR is similar to that achieved in other types of acute nonlymphoblastic leukemia (ANLL) with the same protocols, but the median duration of remission is significantly longer in APL (24 v 9 months) and the percentage of remissions longer than 60 months is also higher in APL (35% v 5%).

Topics: Adolescent; Adult; Aged; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Hemorrhage; Heparin; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Nervous System Neoplasms; Prognosis; Remission Induction; Thioguanine

Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.

Topics: Acute Disease; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Administration Schedule; Heart; Hemorrhage; Humans; Leukemia; Quality of Life; Random Allocation; Respiratory Distress Syndrome; Thioguanine

A patient with relapse of acute granulocytic leukemia developed an Aspergillus infection along the subcutaneous tract of a silicone rubber indwelling central venous catheter. The infection invaded the brachial plexus resulting in paralysis of the right upper extremity and subsequently invaded a major artery of the arm resulting in the demise of the patient. Both an infectious brachial plexus neuritis and fatal hemorrhage secondary to a Hickman catheter are apparently rare.

Topics: Antineoplastic Agents; Aspergillosis; Brachial Plexus; Catheters, Indwelling; Cytarabine; Female; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Middle Aged; Neuritis; Thioguanine

Topics: Adrenal Cortex Diseases; Adrenal Gland Diseases; Animals; Capillary Permeability; Dose-Response Relationship, Drug; Endothelium; Female; Hemorrhage; Horseradish Peroxidase; Hypophysectomy; Microscopy, Electron; Necrosis; Rats; Thioguanine

Intensive care units for hematology or oncology patients consist of rooms free from pathogenic germs and low in microbe content. The units are staffed by doctors and nurses checked to be non carriers of pathogenic germs, and platelet and granulocyte transfusions are available. The first of these rooms, the Unit Fred-Siguier at the Hospital Paul-Brousse (Villejuif), was created for patients receiving bone marrow transplantation. Several units now exist in Europe. Results from two cooperative chemotherapy trials conducted at a European level showed that the number of remissions was double in services equipped with such rooms when compared with other hospital services. The study thus provides further evidence of the great need for such intensive care units.

Topics: Antineoplastic Agents; Blood Transfusion; Bone Marrow Cells; Bone Marrow Transplantation; Cross Infection; Cytarabine; Daunorubicin; Hemorrhage; Humans; Immunosuppression Therapy; Infection Control; Intensive Care Units; Leukemia, Myeloid, Acute; Patient Isolators; Thioguanine

Topics: Adult; Bronchopulmonary Sequestration; Cytarabine; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Lung Diseases; Male; Pneumonectomy; Thioguanine

Topics: Acute Disease; Adolescent; Adult; Aged; Bacterial Infections; Cytarabine; Drug Combinations; Female; Hemorrhage; Humans; Hydroxyurea; Length of Stay; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Patient Isolators; Prednisone; Remission, Spontaneous; Thioguanine

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Alkylating Agents; Anemia; Anemia, Hemolytic, Autoimmune; Busulfan; Chlorambucil; Cyclophosphamide; Folic Acid Antagonists; Hemorrhage; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus Isotopes; Splenectomy; Thioguanine; Triethylenemelamine