thioguanine-anhydrous and Neutropenia

To determine whether granulocyte colony-stimulating factor (G-CSF) administered during acute myelogenous leukemia (AML) induction affects hematopoietic and nonhematopoietic toxicity, length and outcome of induction therapy, event-free survival, overall survival, and prognostic significance of the day 7 bone marrow.. In Children's Cancer Group study 2891, patients were given intensively timed induction with G-CSF (n = 254) after accrual for the regimen without G-CSF (n = 258) was met.. Time to neutropenic recovery after induction courses 1 and 2 was significantly shorter for patients who received G-CSF. Times to platelet recovery were similar regardless of G-CSF use. Effects on incidence of grades 3 and 4 toxicities, infections, or fatal infections were not observed. Use of G-CSF reduced the median length of induction by 9 days and hospital stay by 6 days. Induction remission rates, overall survival, and event-free survival were similar with and without G-CSF. Day 7 bone marrow was prognostic of better long-term outcome. Patients with hypercellular day 7 marrow who received G-CSF had a higher remission rate and event-free survival than patients who did not receive G-CSF.. The incidence of severe toxic event and infection, induction remission rate, overall survival, and event-free survival were comparable regardless of G-CSF use. Use of G-CSF decreased neutropenia duration, hospital stay, and length of induction. Patients with hypercellular day 7 bone marrow who received G-CSF had an induction remission rate and event-free survival superior to those of patients who did not receive G-CSF.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Etoposide; Female; Filgrastim; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Hyperbilirubinemia; Infection Control; Length of Stay; Leukemia, Myeloid; Male; Neutropenia; Prospective Studies; Recombinant Proteins; Remission Induction; Survival Analysis; Thioguanine; Thrombocytosis; Treatment Outcome

Debate and controversy remain as to the optimal post-remission therapy for younger patients with acute myelogenous leukaemia (AML). The aim of this study was to evaluate high-dose treatment (HDT) with autologous bone marrow support (ABMS) as consolidation of first complete remission (CR).. One hundred forty-four patients (AML-M3 excluded, median age 38 years, range 15-49 years) received remission induction therapy comprising: adriamycin 25 mg/m2, days 1-3, cytosine arabinoside (ara-C) and 6-thioguanine, both at 100 mg/m2 bid, days 1-7. Patients in whom CR was achieved received two further cycles of the same treatment prior to bone marrow being harvested and cryopreserved. HDT comprised ara-C: 1 g/m2 b.i.d. x six days and total body irradiation (TBI): 200 cGy b.i.d. for three days. Thawed autologous marrow was then re-infused.. Complete remission was achieved in 106 of 144 patients (73%) who were thus eligible to receive ara-C + TBI + ABMS; 61 actually received it. Following HDT, the median time to neutrophil recovery (> 0.5 x 10(9)/l) was 25 days (range 11-72 days) and to platelet recovery (> 20 x 10(9)/l), 42 days (range 15-159 days). There were eight treatment-related deaths. Analysis by 'intention to treat' shows both remission duration (log-rank, P = 0.001) and survival (log-rank, P = 0.004) to be significantly longer for the 106 patients eligible to receive HDT than for a historical control group (n = 133) who received identical remission induction and consolidation therapy but without ara-C + TBI + ABMS. With a median follow-up of 5.5 years, 39 of 106 patients remain in CR (37%) and 54 (51% of those in whom CR was achieved) remain alive, with a predicted actuarial survival of 52% at 5 years.. The addition of ara-C + TBI + ABMS to conventional consolidation therapy significantly improved remission duration and survival over those of a historical control group of patients with AML (aged < 50, AML-M3 excluded). HDT was, however, associated with significant treatment-related mortality and slow blood count recovery. The use of ara-C + TBI supported by peripheral blood progenitor cells should make the treatment safer and more widely applicable in AML.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Prognosis; Survival Analysis; Thioguanine; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation

Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70%. However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity. Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults. The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy. Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007). In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02). Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02). A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007). With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Etoposide; Female; Fever; Filgrastim; Gastrointestinal Diseases; Germany; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Ifosfamide; Infant; Infection Control; Life Tables; Male; Mercaptopurine; Methotrexate; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prospective Studies; Recombinant Proteins; Risk; Survival Analysis; Thioguanine; Vincristine; Vindesine

The cytotoxic activity of 6-mercaptopurine (6-MP) is affected by thiopurine methyltransferase (TPMT), a genetically regulated and variable intracellular enzyme. 6-Thioguanine (6-TG), a closely related thiopurine, is less affected by that enzyme and so it may be a more reliable drug-at least for patients with constitutionally high TPMT activity. We attempted to assess its suitability as an alternative by comparing the pharmacokinetics of both drugs in a small group of children with lymphoblastic leukaemia (ALL). Patients were included who were in their second or subsequent remission, who would otherwise have received 6-MP, and on whom pharmacokinetic data concerning 6-MP metabolism had been collected in a previous remission. Plasma 6-TG concentrations were assayed following an oral dose of 40 mg m-2, and the accumulation and fluctuation of intracellular (erythrocyte, RBC) 6-TG nucleotides (6-TGNs) were measured at regular intervals during daily oral therapy. Seven children were studied. Plasma 6-TG concentrations were low and cleared within 6 h of oral dosing. At 7 days, 6-TGN concentrations ranged from 959 to 2361 pmol 8 x 10(-8) RBCs, in all cases significantly higher (P = 0.002) than those produced by the same patients on 6-MP. After a total therapy time of 35 patient months, a modest rise of alanine aminotransferase was seen on one occasion, otherwise no toxicity apart from myelosuppression was encountered. In the context used, 6-TG appears well tolerated and produces higher concentrations of intracellular cytotoxic metabolites than 6-MP. For children constitutionally 'resistant' to the traditional drug, if not all, it may be a preferable alternative.

Topics: Adolescent; Child; Erythrocytes; Female; Humans; Kinetics; Male; Mercaptopurine; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thioguanine; Thrombocytopenia; Time Factors

The purpose of this study was to assess the frequency of blood stream infections (BSIs) during neutropenia in different cycles of intensive chemotherapy treatment in acute myeloid leukemia (AML). The register data of 327 consecutive patients aged 16-66 years having de novo AML between September 1992 and December 2001 were prospectively gathered in five Finnish tertiary care leukemia centers. The patients had not received fluoroquinolone prophylaxis. Reported BSI rates were compared during neutropenia in four chemotherapy treatment cycles (C). There were 956 treatment episodes, with 456 (47.7%) positive blood cultures. BSI was monomicrobial in 327 episodes (71.7%) and polymicrobial in 129 (28.3%). The overall incidence rate (per 1,000 hospital days) for BSI was 13.2, varying from 6.8 in CI after idarubicin, conventional-dose cytarabine, and thioguanine to 15.6 in CII, 15.8 in CIII, and 17.6 in CIV. The distribution of monomicrobial gram-positive BSIs was as follows: CI, 71.7%; CII, 62.8%; CIII, 53.3%; CIV, 36.6%; and CI-IV together, 43.2%. The most common finding in the four different cycles was coagulase-negative staphylococci (38.3 to 30.6%). Viridans group streptococci were most commonly observed (in 20.4% of positive blood cultures) during CII after high-dose cytarabine and idarubicin treatments. The distribution of monomicrobial gram-negative BSIs was as follows: CI, 21.7%; CII, 36.3%; CIII, 45.7%; CIV, 46.9%; and CI-IV together, 37.9%. A great variation of incidence and types of microorganisms between AML chemotherapy cycles was found. It would be more reasonable to analyze chemotherapy cycle-based BSI results rather than the overall results.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bacteria; Blood; Cytarabine; Female; Finland; Humans; Idarubicin; Incidence; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Prospective Studies; Sepsis; Thioguanine; Young Adult

Neutrophilic eccrine hidradenitis (NEH) is an infrequent, self-limited inflammatory dermatosis characterized by a neutrophilic infiltrate around the eccrine glands. Clinically, it presents with different types of lesions. NEH occurs most frequently in patients who have undergone chemotherapy for hematologic neoplasms. We present a case of NEH in a 70-year-old neutropenic male who received thioguanine for acute myeloid leukemia. The erythematous plaques disappeared in 3-4 weeks. The histological findings were compatible with NEH. Skin cultures ruled out infectious causes.

Topics: Aged; Antimetabolites, Antineoplastic; Eccrine Glands; Hidradenitis; Humans; Male; Neutropenia; Thioguanine

Infections still remain a major cause of therapy-associated morbidity and mortality in children with acute myeloid leukemia (AML). To improve supportive care measurements, detailed information on frequency and characteristic features of infectious complications is needed. We retrospectively analyzed the medical charts of 304 children, treated in 30 hospitals according to the multi-institutional clinical trial AML-BFM 93. Overall, 855 infectious complications occurred in 304 patients (fever without identifiable source (n=523; 61.2%), clinically (n=57; 6.7%) and microbiologically documented infections (n=275; 32.1%)). Neutropenia was present in 74.1% of the infectious episodes. In all, 20 patients died of infection-associated complications (15/276 (5.4%) patients without and 5/28 (17.9%) with Down syndrome), most of them during early induction therapy (n=11). Blood stream infections occurred in 228 episodes (Gram-positive (n=202) and Gram-negative (n=42) pathogens). Invasive fungal infection was probable or proven in 15 patients. In 113 out of the 855 infectious episodes (13.3%), pneumonia was radiologically diagnosed. Better strategies of supportive care might help to improve overall survival in children undergoing chemotherapy for AML. Therefore, children with AML should be treated in specialized pediatric centers, and there should be a very low threshold to readmit patients, in particular patients with pulmonary symptoms.

Topics: Acute Disease; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacteria; Child; Child, Preschool; Clinical Trials as Topic; Cytarabine; Down Syndrome; Etoposide; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant; Infant, Newborn; Leukemia, Myeloid; Male; Mitoxantrone; Neutropenia; Prospective Studies; Retrospective Studies; Thioguanine

Severe infections are a major problem in patients suffering from acute nonlymphocytic leukemia (ANLL) undergoing myeloablative chemotherapy. Possible factors leading to infectious complications in these patients are suppressed immune defense mechanisms existing prior to therapy, including those involving the neutrophil granulocyte department. In this study we investigated whether neutrophil function as measured by oxidative burst and phagocytosis before the start of treatment correlates with the severity of infection after therapy. Forty-four patients were included, 27 men and 17 women. Their median age was 46 years (range 20-70 years). According to the development of infectious complications the patients were assigned retrospectively to group 1 (no or only mild infections, n = 29) or to group 2 (severe infection or death due to infection, n = 15). The phagocytic activity was significantly reduced in group 2 as compared with group 1 [113.7+/-13.7 (SEM) vs 170.0+/-19.2, mean channel fluorescence; p =0.04]. In contrast, the oxidative burst as measured by FMLP stimulation was pronounced but not significantly enhanced in group 2 (24.8+/-6.1 vs 14.5+/-3.4, mean channel fluorescence). In conclusion, patients with severe infections after chemotherapy might already have preactivated neutrophils with suppressed function prior to treatment. Thus, evaluating function parameters could help to estimate the individual risk of infection for a patient with ANLL.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Fever; Humans; Idarubicin; Immunocompromised Host; Infections; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Mitoxantrone; N-Formylmethionine Leucyl-Phenylalanine; Neutropenia; Neutrophils; Phagocytosis; Respiratory Burst; Retrospective Studies; Risk Factors; Thioguanine; Vidarabine

As a prelude to a nationwide randomized trial of thioguanine (TG) versus mercaptopurine (MP) for childhood lymphoblastic leukaemia we compared a pilot group of 23 children taking TG with a matched group taking MP. We assessed drug tolerance based on haematological toxicity and measured erythrocyte (RBC) concentrations of thioguanine nucleotides (TGN). The median tolerated dose of TG was 30 mg/m2 compared to 55 mg/m2 for MP. There was no difference in the pattern of anaemia or neutropenia between the two groups, but dose-limiting thrombocytopenia was more evident in the TG children (P< 0.001), four of whom had a decrease in platelet count to <20 x 10(9)/l compared to only one on MP. The median RBC TGN concentration for those on 40 mg/m2 TG was 1726 pmol/8 x 10(8) RBCs compared with 308 pmol/8 x 10(8) RBCs for those on 75 mg/m2 MP (P< 0.0001). There was an inverse correlation between RBC TGNs and neutrophil count in the MP group but not in those on TG. No correlation between metabolite concentration and thrombocytopenia was found in either group. These results provide further evidence that TG has a selective effect on platelets. They also showed that RBC TGN were, on average, 5-fold higher in those taking TG but did not obviously relate to myelotoxicity as found in children on MP. The higher concentrations seen may partly reflect the erythrocyte's ability to metabolize TG directly to TGN by pathways not open to MP.

Topics: Adolescent; Antimetabolites, Antineoplastic; Child; Child, Preschool; Female; Humans; Infant; Lymphocyte Count; Male; Mercaptopurine; Neutropenia; Neutrophils; Nucleotides; Platelet Count; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thioguanine; Thrombocytopenia

27 patients with relapsed/refractory non-Hodgkin lymphoma (NHL) received combination chemotherapy with prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET). 25 patients are evaluable for response. 7 (26%) obtained a complete response and one (4%) a partial response. The median survival for the entire group was 6 months. 2 patients are currently alive without disease, 1 of whom has received further therapy. The regimen was intensely myelosuppressive, but was well tolerated. The complete response rate and median survival figures are comparable to previous studies of salvage therapy confirming the poor prognosis for relapsed NHL and emphasising the need for prospective randomised studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Etoposide; Female; Humans; Lomustine; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neutropenia; Prednisolone; Prognosis; Prospective Studies; Thioguanine

To reduce critical neutropenia after chemotherapy (CT) for acute myeloid leukemia (AML) we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients over the age of 65 years with newly diagnosed AML and to patients with early or second relapse. CT was 9-day 6-thioguanine, ara-C, and daunorubicin (TAD9) in newly diagnosed AML and sequential high-dose ara-C and mitoxantrone (S-HAM) for relapse. In patients whose bone marrow was free from blasts a continuous intravenous infusion of GM-CSF 250 micrograms/m2/d started on day 4 after CT. Thirty-six patients entered the study and 30 of them did receive GM-CSF. For comparison, a historical control group of 56 patients was used. Complete remission rate was 50% (18 of 36) versus 32% in controls (P = .09), and early death rate was 14% versus 39% (P = .009). Treatment with GM-CSF was not associated with major adverse events. Two patients showed a marked leukemic regrowth that was completely reversible in one patient and appeared to be GM-CSF independent in the other patient. Remission duration does not seem to be reduced after GM-CSF. Under GM-CSF the blood neutrophils recovered 6 and 9 days earlier in the TAD9 (P = .009) and S-HAM (P = .043) groups associated with a rapid clearance of infections in most patients. We conclude that GM-CSF was of therapeutic benefit to our patients and this provides a basis for larger controlled trials.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Middle Aged; Mitoxantrone; Neutropenia; Recombinant Proteins; Remission Induction; Thioguanine

Eighty two children with acute lymphoblastic leukaemia presenting at this hospital received one or two modules of intensive chemotherapy to consolidate remission. Modules were given after four and roughly 19 weeks on treatment. Each included two doses of daunorubicin (45 mg/m2/day), cytosine arabinoside (100 mg/m2 twice daily X 5), etoposide (100 mg/m2/day X 5), and 6-thioguanine (80 mg/m2/day X 5). A total of 132 courses were given. This study included all new patients except girls aged 1-14 years with presenting leucocyte count less than 20 X 10(9)/l. Twenty patients with recurrent disease were also included. The first 32 patients were given cytosine as a 24 hour infusion, but combined with the other agents this was associated with severe intestinal toxicity, which necessitated a change to a less toxic 12 hourly bolus regimen. The complications of the module are reviewed in terms of myelosuppression, enterotoxicity, infection, and other clinical problems encountered. All patients became profoundly neutropenic and thrombocytopenic. The latter was significantly more severe after cytosine infusion. Overall, 64% received platelet transfusions and 85% were re-admitted with fevers requiring intravenous antibiotics for between four and 56 days. Gastrointestinal toxicity with the modified module occurred in 38% of patients and was severe in 13%. This intensification module has been adopted by the Medical Research Council Working Party on Childhood Leukaemia for use in a multicentre study (UKALL X) and the details of the problems encountered in the pilot study may be of value to other centres now using this protocol.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Daunorubicin; Etoposide; Female; Humans; Infant; Infections; Leukemia, Lymphoid; Male; Neutropenia; Pilot Projects; Thioguanine; Thrombocytopenia

The effect of folic acid supplements on 6-mercaptopurine remission maintenance therapy in lymphoblastic leukaemia (ALL) was investigated in a retrospective longitudinal study of 10 children. Red cell concentrations of 6-thioguanine nucleotide, a cytotoxic metabolite of 6-mercaptopurine, were measured and the peripheral neutrophil count was used as an index of myelosuppression. During the control period of the study there were significant correlations between 6-mercaptopurine dose and 6-thioguanine nucleotide concentration (rs = 0.59, P less than 0.0005) and between 6-thioguanine nucleotide concentration and the peripheral neutrophil count at 14 days (rs = 0.58, P less than 0.0005). These relationships were absent when the same children were subsequently taking folate supplements. Also when taking folate supplements the children tolerated significantly more 6-mercaptopurine (P less than 0.005) for a significantly longer time (P less than 0.005) before neutropenia developed. There was no significant difference in red cell 6-thioguanine nucleotide concentration in the absence and presence of folate supplements. These findings suggest that folate supplements may interfere with remission maintenance therapy in ALL.

Topics: Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Female; Folic Acid; Humans; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Neutropenia; Neutrophils; Thioguanine

6-Mercaptopurine is extensively used in the treatment of childhood lymphoblastic leukaemia to prolong the duration of remission achieved with other drugs. The response to remission maintenance therapy varies widely. We investigated the relationship between red blood cell 6-thioguanine nucleotide, a metabolite of 6-mercaptopurine, and myelosuppression in 22 children with acute lymphoblastic leukaemia in remission. The peripheral neutrophil count was used as an index of myelosuppression. 6-Mercaptopurine dose was related to 6-thioguanine nucleotide concentration (r = 0.4; P less than 0.001; n = 90; y = 18.51 + 0.36 x). Large individual variations around the regression line are observed. Neither 6-mercaptopurine dose nor 6-thioguanine nucleotide concentration was related to the neutrophil count at the time of sampling (day 0) or 7 days later. Both 6-mercaptopurine dose and 6-thioguanine nucleotide concentration correlated with the neutrophil count at day 14 (r = -0.33; P less than 0.01; n = 90 and r = -0.3; P less than 0.01; n = 90 respectively). This delay is compatible with a cytotoxic action on bone marrow stem cells. Excluding children with other, uncontrolled, potentially myelosuppressive influences the correlation between 6-thioguanine nucleotide concentration and neutropenia improved (r = -0.6; P less than 0.001; n = 37). A significant degree of neutropenia was observed by day 14 if the 6-thioguanine nucleotide concentration (day 0) was greater than 210 pmol/8 X 10(8) RBCs. The assay of 6-thioguanine nucleotide may highlight those individuals with pharmacokinetic resistance. Two children on continuous high dose 6-mercaptopurine, had low red blood cell 6-thioguanine nucleotide concentrations and neutropenia was not observed.

Topics: Adolescent; Agranulocytosis; Bone Marrow Diseases; Child; Child, Preschool; Erythrocytes; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Neutropenia; Thioguanine

We describe 3 cases of acute graft-versus-host (GVH) disease in patients with acute myeloid leukaemia following transfusions taken from non-HLA-identical healthy donors. The leucocyte transfusions were given because of severe bone marrow aplasia and granulocytopenia following leukaemia induction treatment. The first patient had an acute GVH reaction with an erythrodermia-like skin reaction all over and associated with severe abdominal cramping, enlarged liver and pathological liver function tests. The second patient had a relatively mild skin reaction and enlarged liver. Both died of severe pulmonary infection. The third patient also had a mild skin reaction and enlarged liver. He died of pulmonary embolism. The diagnosis of GVH of the latter 2 cases was made on skin biopsy. The autopsy samples revealed in all cases a heavy lymphocytic infiltration of the kidneys and liver portal area. Until more precise guidelines can be established, irradiation of blood cell products given to patients with neutropenia due to leukaemia induction treatment should be considered.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; Graft vs Host Disease; Humans; Leukemia, Myeloid, Acute; Leukocytes; Male; Methotrexate; Middle Aged; Neutropenia; Prednisolone; Prednisone; Thioguanine; Transfusion Reaction; Vincristine

Topics: Antineoplastic Agents; Bacterial Infections; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Neutropenia; Prednisone; Thioguanine

In an attempt to convert the bone-marrow population from Philadelphia-chromosome (Ph-1) positivt to partially or wholly Ph-1 negative, thioguanine was used as primary therapy in seven patients with chronic granulocytic leukaemia (C.G.L.). Although eight episodes of neutropenia were induced, prolonged remission or conversion to Ph-1-negativity was not achieved in any patient. However, thioguanine was at least as effective as busulphan for initial therapy in C.G.L., and had the advantage of rapid reversibility of haemopoietic depression when discontinued. Thioguanine merits further evaluation as an agent for the management of C.G.L. in its chronic phase.

Topics: Adult; Alkaline Phosphatase; Allopurinol; Chromosomes, Human, 21-22 and Y; Drug Evaluation; Drug Therapy, Combination; Female; Hematopoietic Stem Cells; Hemoglobins; Humans; Leukemia, Myeloid; Leukocyte Count; Male; Middle Aged; Neutropenia; Neutrophils; Thioguanine