thioguanine-anhydrous and Leukemia--Monocytic--Acute

A trial of maintenance chemotherapy of nonlymphoblastic acute leukemia led to a comparison of two groups of patients in complete remission. Group 1 (14 patients) received only monthly reinduction chemotherapy. Group 2 (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukemic cells. While the duration of the first complete remission was unmodified, the overall survival time and, above all, survival after the first relapse were prolonged in group 2 chemoimmunotherapy. These results were all the more marked when a homogeneous group of patients having received the same induction chemotherapy were considered.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Clinical Trials as Topic; Cytarabine; Daunorubicin; Female; Humans; Immunotherapy; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Middle Aged; Mycobacterium bovis; Thioguanine

In order to determine whether the use of a sequence of chemotherapeutic regimens plus BCG could produce longer durations of remission in adult acute nonlymphocytic leukemia than maintenance therapy with cytosine arabinoside, 6-thioguanine, plus BCG, a randomized study was performed at Washington University. Upon achieving complete remissions with daunorubicin plus cytosine arabinoside, 14 patients were randomized to receive either: Regimen A--cytosine arabinoside, 6-thioguanine, plus BCG each month; or regimen B--sequential regimens consisting of: 1) azacytidine daily for five days; 2) cyclophosphamide plus cytosine arabinoside daily for four days, prednisone daily for five days, plus vincristine on the first day; 3) prednisone, 6-mercaptopurine, and methotrexate daily for five days plus vincristine on the first day; and 4) cytosine arabinoside, 6-thioguanine, plus BCG. Each of the sequential regimens was given during consecutive months, and the cycle was then repeated starting with the first regimen. Median duration of complete remission was 27 months for 8 patients randomized to receive Regimen A, compared to only seven months for 6 patients receiving Regimen B (P less than 0.05). The median survival time of patients on Regimen B was only 14 months, and has not yet been reached in Regimen A. At 40 months after diagnosis, 75% of patients on Regimen A remain alive (P less than 0.05). Toxicity was equal for the maintenance regimens. Therefore, maintenance therapy with cytosine arabinoside, 6-thioguanine, plus BCG may be superior to the sequence of chemotherapy regimens plus BCG which was employed.

Topics: Adolescent; Adult; BCG Vaccine; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Prognosis; Thioguanine; Time Factors

194 adults with acute leukaemia were randomly allocated to be treated with a combination of daunorubicine, cytarabine and prednisone either with (RAP + T) or without (RAP) thioguanine. A remission was achieved in 37% of 101 patients treated with RAP and in 35% of 93 patients treated with RAP + T. The survival and length of remission were similar in both groups. Neither regimen was superior to the other in any type of leukaemia nor in any age group of patients. In 9 of the patients failing to remit with RAP treatment a remission was obtained with other chemotherapy, while none of the patients not responding to RAP + T achieved a remission with further chemotherapy.

Topics: Acute Disease; Adolescent; Adult; Aged; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Thioguanine

One hundred patients were entered in a cooperative study comparing the efficacy of two different regimens in the induction treatment of acute nonlymphocytic leukemia (ANLL). Patients were randomly allocated to receive either the DAT or VAT combination; half of the patients were also randomized to receive CNS prophylaxis including intrathecal methotrexate + prednisone and cranial irradiation. Consolidation and maintenance therapy were uniform in responding patients. Out of 82 evaluable patients 41 (50%) attained complete remission (CR) with no significant difference between the two regimens. Median remission duration was slightly longer in the DAT group (32.5 vs 22 weeks); median survival was 34 weeks for all evaluable patients with no difference between the two schedules. Meningeal relapse occurred only in two patients after 19 and 99 weeks of continuous remission. Fourteen patients are still alive after 61 to greater than or equal to 155 weeks, of whom seven are in their initial remission (six in the DAT and one in the VAT group). We conclude that 1) DAT and VAT are equally effective in inducing CR in a high proportion of ANLL patients; 2) until marrow remission can be prolonged significantly, preventing CNS leukemia will not have any significant impact of the course of ANLL.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Meningeal Neoplasms; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Thioguanine; Time Factors; Vincristine

The incidence of acute leukemia in children with Down syndrome (DS) is high as compared to general population. Recent findings have demonstrated that DS children with acute myeloid leukemia (AML) have the highest event free survival rates with high dose cytosine arabinoside (Ara-C). We present 3 year-old DS female child with AML-M5, whose chromosomal analysis revealed constitutional t(21;21) alongwith del(5)(q31q33) and a unique translocation t(16;20)(q13;q12). After chemotherapy, child achieved complete clinical remission. Karyotype analysis of remission marrow showed disappearance of abnormal clone of der(20) t(16;20)(q13;q12), del(5q) indicating cytogenetic remission too. This case alongwith supportive literature indicate that pediatric DS-AML is a distinct biologic sub-group differs from that of non-DS-AML with respect to chemosensitivity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Chromosome Aberrations; Chromosome Deletion; Cytarabine; Daunorubicin; Down Syndrome; Female; Humans; Leukemia, Monocytic, Acute; Thioguanine; Translocation, Genetic

IgA deficiency is a relatively common congenital immunodeficiency in children. It can either be asymptomatic or lead to frequent infections, most often of the sinuses and lungs. Intensive chemotherapy for acute leukemia is also profoundly immunosuppressive and can be complicated with life-threatening infections, usually associated with neutropenia and prolonged lymphopenia in the post-bone marrow transplant setting. Isolated, acquired immunoglobulin deficiency that occurs during treatment has been described but is usually transient. In this report, the authors describe a patient with infant acute myelogenous leukemia with acquired, persistent IgA deficiency.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Humans; IgA Deficiency; Immunoglobulins, Intravenous; Infant; Leukemia, Monocytic, Acute; Male; Thioguanine

Topics: Adult; Antigens, CD34; Antimanic Agents; Antineoplastic Combined Chemotherapy Protocols; Bipolar Disorder; Blood Cell Count; Cytarabine; Daunorubicin; Drug Synergism; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Idarubicin; Leukapheresis; Leukemia, Monocytic, Acute; Lithium Carbonate; Mitoxantrone; Recombinant Proteins; Remission Induction; Thioguanine

Extramedullary masses as features of acute monoblastic leukemia are rare. Acute monoblastic leukemia is an uncommon type of nonlymphocytic leukemia that generally first manifest with signs and of bone marrow failure, articular and/or neurological symptoms. This study describes one patient with acute monoblastic leukemia in whom the initial manifestation of the disorder was related to testicular mass.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Doxorubicin; Humans; Leukemia, Monocytic, Acute; Leukemic Infiltration; Male; Testis; Thioguanine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carcinoma in Situ; Cyclophosphamide; Cytarabine; Daunorubicin; Diagnosis, Differential; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Monocytic, Acute; Mitoxantrone; Remission Induction; Thioguanine; Transplantation, Autologous; Uterine Cervical Dysplasia

Recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-SCF) is currently being tested in clinical trials for the treatment of acute myeloid leukemias with two main intentions: reduction of neutropenia and recruitment of leukemic blasts into cell cycle to enhance cytarabine (ara-C) mediated cytotoxicity. We report a case of a fatal spleen rupture in a patient with acute monocytic leukemia (AML M5b) who was treated according to a clinical phase I/II protocol with rh GM-CSF priming and standard induction chemotherapy TAD 9 (thioguanine/ara-C/daunorubicin). During treatment we observed rapidly rising peripheral blast counts and the development of an acute abdomen. Ultrasound examination revealed splenomegaly due to diffuse cellular infiltration and spleen rupture. The patient died 17 days later due to pneumonia and renewed spleen hemorrhage. Bone marrow progenitor assays before treatment showed exclusive growth of monocytoid blast cell colonies (CFU-L). Colony growth could be stimulated with rh GM-CSF and blocked dose-dependently by a monoclonal anti-GM-CSF antibody. CFU-L proliferation also increased after stimulation with rh interleukin-3 (rh IL-3) and supra-additively with rh granulocyte colony-stimulating factor (rh G-CSF) combined with rh GM-CSF. Furthermore, rh GM-CSF induced surface marker expression of CDw 65 and CD 11b on isolated CFU-L blasts. After short-term suspension culture, rh GM-CSF enhanced the expression of CD 29- and CD 11b-adhesion molecules on peripheral blast cells. In summary, this case represents a fatal spleen rupture occurring during rh GM-CSF priming and induction chemotherapy for acute monocytic leukemia. Although the etiology of this spleen rupture remains uncertain, in view of our data we suggest special caution, when further testing this therapy protocol in acute leukemias with monocytic subtype and high peripheral blast cell counts.

Topics: Antigens, Neoplasm; Antigens, Surface; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Cells; Cell Adhesion Molecules; Cytarabine; Daunorubicin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Leukemia, Monocytic, Acute; Middle Aged; Neoplastic Stem Cells; Recombinant Proteins; Splenic Rupture; Thioguanine; Tumor Cells, Cultured

A patient with nonfamilial peripheral neurofibromatosis (NF) (von Recklinghausen's disease) is reported who contracted acute monocytic leukemia at 60 years of age. In the course of the illness, myelonecrosis developed and the patient died 4 months later due to a therapy-resistant bone marrow relapse. This association of the two illnesses would appear to confirm reports on an increased incidence of nonlymphatic leukemia and NF. Such an association is seen during childhood as juvenile chronic leukemia, but it is uncommon in adulthood.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blotting, Southern; Cytarabine; Daunorubicin; Humans; Leukemia, Monocytic, Acute; Male; Middle Aged; Neoplasms, Multiple Primary; Neurofibromatosis 1; Thioguanine

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Doxorubicin; Humans; Hydrocortisone; Leukemia, Monocytic, Acute; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Testicular Neoplasms; Thioguanine

A longitudinal observation of a patient with idiopathic refractory sideroachrestic anemia (IRSA) progressing to acute mixed lymphoblastic-myelomonoblastic leukemia is reported. The leukemia was characterized by morphology, immunological cell markers, and dissociated clinical responsiveness to vincristine/prednisone and arabinosylcytosine/6-thioguanine. Attention is paid to the hematological changes prior to leukemia development. Acute leukemia was best heralded in this patient by a severe deterioration of dyserythropoiesis and by an increase of blasts in the marrow to more than 5%. The observed preleukemic features are compared to those described in the literature.

Topics: Aged; Anemia, Sideroblastic; Bone Marrow Examination; Cerebrospinal Fluid; Cytarabine; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Pneumonia; Prednisone; Thioguanine; Tuberculosis, Miliary; Vincristine

Topics: Cytosine; Daunorubicin; Female; Humans; Leukemia, Monocytic, Acute; Middle Aged; Polycythemia Vera; Recurrence; Thioguanine

Cell kinetic changes induced in the marrow blasts by treatment with a triple cytotoxic regimen including daunorubicin, cytosine arabinoside and 6-thioguanine (DAT) were investigated in 6 previously untreated acute nonlymphocytic leukemia patients. A decrease in the labeling and mitotic indices was consistently observed 24 h after administration of daunorubicin, suggesting a G2 block and a preferential lytic effect on the S-phase cells operated by the drug. Conversely, cytosine arabinoside and 6-thioguanine in combination induced a series of kinetic perturbations variable from case to case; however, three principal patterns of kinetic response were recogized and discussed in detail. Useful information for the planning of a more rational antileukemic therapy can be drawn from a systematic study of the kinetic effects induced by drug combinations.

Topics: Adolescent; Adult; Bone Marrow; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitotic Index; Thioguanine

Tn polyagglutination (persistent mixed-field polyagglutination) was detected in the blood of a 66-yr-old male laborer at the time of a splenectomy for life-threatening thrombocytopenia. Confirmation that the polyagglutination was caused by Tn activation was established by the use of lectins, by failure of the patient's red cells to react with sera from other patients with Tn polyagglutination, by weak aggregation with polybrene, by low red cell sialic acid levels, and by the persistence of polyagglutination over several years of testing. Two years after the discovery of the Tn polyagglutination, the patient developed acute myelomonocytic leukemia. Vigorous chemotherapy regimens resulted in clinical remission of the leukemia and the Tn polyagglutination. This report describes the first known case of Tn polyagglutination preceding the development of acute myelogenous leukemia.

Topics: Aged; Cytarabine; Daunorubicin; Hemagglutination; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Splenectomy; Thioguanine; Thrombocytopenia

The need for prophylactic therapy of the central nervous system in adult acute nonlymphoblastic leukemia has been suggested but no proven. Over a 4-year period from January 1973, to December 1976, we have maintained 40 patients achieving complete remission on a regimen consisting of monthly courses of Cytosine Arabinoside and 6-thioguanine. Twenty patients remain in remission with a predicted median remission duration for the entire group of 14.5 months. Thirty nine of the patients did not have central nervous system leukemia at diagnosis, and only one of these patients (2.6%) has had remission tenance regimen there is little need for central nervous system prophylaxis in adult acute nonlymphoblastic leukemia.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission, Spontaneous; Thioguanine

Two distinct cell populations with lymphoblastic and monocytic characteristics were separated and characterized by multiple cell markers in a patient with terminal transferase-positive acute acute leukemia. The clinical course and sequential cell marker studies were consistent with the interpretation of a defect at the level of a common stem cell giving rise to a terminal transferase--positive lymphoblastic cell population at diagnosis and, following initial therapy, a terminal transferase--negative monocytic population.

Topics: Adult; Cell Separation; Female; Flucytosine; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Lymphocytes; Monocytes; Nucleotidyltransferases; Prednisone; Thioguanine; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Marrow Transplantation; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Hematopoiesis; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lomustine; Male; Middle Aged; Neoplasms; Remission, Spontaneous; Thioguanine; Transplantation, Autologous

Fifteen patients with acute leukemia resistant to standard chemotherapy were treated by bone marrow transplantation from HLA-matched siblings after conditioning with a new combination chemotherapy/radiation therapy regimen--SCARI. SCARI consists of 5 days of high-dose cytosine arabinoside and 6-thioguanine followed by 3 days of daunorubicin. After a rest period, cyclophosphamide and total-body irradiation are given sequentially. This regimen had acceptable morbidity. Median survival was 169 days. Overall survival and disease-free survival was 27% at over 11 months. Relapse rate was 13% of the entire group and 30% by actuarial projection. Relapses were late and initially extramedullary. Deaths from causes other than leukemia occurred early secondary to fungal infection and late secondary to interstitial pneumonia (frequently cytomegalovirus). Graft-versus-host disease and graft rejection were not causes of mortality. In these patients conditioned with SCARI, leukemic recurrences were infrequent but infectious complications were a major hazard.

Topics: Adolescent; Adult; Bone Marrow Cells; Bone Marrow Transplantation; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Graft vs Host Reaction; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Thioguanine; Time Factors; Transplantation, Homologous

Maintenance chemotherapy consisting of weekly oral 6-thioguanine and intramuscular cytosine arabinoside was administered to 24 adult patients with acute non-lymphocytic leukaemia in complete remission. The median duration of complete remission was 16-5 months, with 9 patients (38%) still in their first remission after 18--56 months. 33% of the patients have been in continuous remission for over 2 yr, 21% for over 3 yr, and 12-5% for over 4 yr. Median survival so far is 22-5 months. This maintenance regimen is well tolerated, is easily administered on an outpatient basis, and produces substantial numbers of long-term remissions.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cytarabine; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission, Spontaneous; Thioguanine; Time Factors

Topics: Adult; Blood Transfusion; Cytarabine; Daunorubicin; Female; Hair; Humans; Infant, Newborn; Leukemia, Monocytic, Acute; Male; Pregnancy; Pregnancy Complications, Hematologic; Thioguanine

Improvement in the management of acute leukemia in adults has not progressed nearly so rapidly as has the treatment of childhood leukemia. One important difference is that most adults have myeloblastic or related forms of the disease (AML), whereas the majority of children have lymphoblastic leukemia (ALL). However, even adults with ALL fail to respond as well to a similar regimen as do children with the same type of leukemia. In a recent series of patients with ALL who were treated with the complex multiple drug "L-2" protocol, the incidence of complete remission in adults was 78% vs. 99% in children, and the median duration of remission was only 24 months in the adults, whereas it has not yet been reached in the children and is projected to be over 4 years. In AML and the related nonlymphoblastic forms of acute leukemia, therapy is still unsatisfactory in both adults and children. With the best current drug treatment schedules, the incidence of complete remission is now better than 50%, but it is often difficult to compare the exact remission rates in different series because of differences in reporting results. In adults treated with the multiple drug "L-6" protocol, the incidence of remission in previously untreated patients was 56% and the median duration of remission was 10 months. The median survival of all patients (responders and non-responders) was 1 year whereas that of responders only was 2 years. It is encouraging that a significant proportion of those patients with AML who have complete remissions now remain in remission for extended periods; about 45% of patients responding to the "L-6" protocol remained in remission over 1 year, and 18% have been in continuous remission for 2 to over 4 years. Even after discontinuing treatment, some patients with AML stay in remission for long periods, and it is possible that some of them may have been cured. If this proves to be true, it becomes of great importance to determine what is different about the patients who do exceptionally well as compared to the majority who continue to die within a year. However, no consistent nor distinctive favorable prognostic features have yet been identified.

Topics: Adolescent; Adult; Aged; Asparaginase; Carmustine; Child; Cytarabine; Daunorubicin; Female; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Methotrexate; Middle Aged; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Adult; Aged; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Thioguanine

Topics: Adolescent; Adult; Aminosalicylic Acids; Asparaginase; Blood Cells; Bone Marrow; Bone Marrow Cells; Daunorubicin; Diagnosis, Differential; Doxorubicin; Esterases; Histocytochemistry; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Middle Aged; Peroxidases; Prednisolone; Thioguanine; Vincristine

Topics: Adrenal Cortex Hormones; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Thioguanine; Vincristine

Topics: Adult; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Thioguanine

Topics: Adult; Antineoplastic Agents; Asparaginase; Child; Cytarabine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Humans; Immunotherapy; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Prednisone; Remission, Spontaneous; Thioguanine; Time Factors; Vincristine

Topics: Adult; Aged; Blood Cell Count; Bone Marrow Cells; Bone Marrow Examination; Child; Cytarabine; Densitometry; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Adolescent; Adult; Aged; Cytarabine; Dosage Forms; Female; Humans; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Thioguanine