allopurinol and Hematologic-Diseases

Topics: Allopurinol; Clinical Trials as Topic; Drug Synergism; Drug Therapy, Combination; Hematologic Diseases; Humans; Urate Oxidase; Uric Acid

Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) with the benefit of overcoming side effects regularly associated with thiopurine monotherapy and poor responses. Concerns regarding safety remain, while a layer of complexity has been added by the trend toward treatment directed by red cell thioguanine nucleotide (TGN) profiling. We report on the clinical efficacy and safety of LDAA use in IBD undirected by metabolite profiling.. Observational study of clinical practice from a single IBD center. Patient outcomes were defined clinically based on established activity scores and corticosteroid withdrawal. Red cell TGN was monitored only for suspected nonadherence.. Overall, 113/164 (69%) patients with Crohn's disease and 83/136 (61%) patients with ulcerative/unclassified colitis had a clinical response by the end of follow-up (median 19 months), while 85 (52%) patients with Crohn's disease and 74 (54%) patients with ulcerative/unclassified colitis were in clinical remission. Clinical response was seen in 45/57 (79%) patients with Crohn's disease and 34/53 (64%) patients with ulcerative/unclassified colitis who were thiopurine naive, had active IBD, and received LDAA as the first line immunomodulator, while in 35 (61%) and 28 (53%), respectively, remission was achieved. LDAA was stopped in 20/300 (7%) patients because of side effects, all of which resolved on drug cessation.. This is the largest cohort supporting the favorable safety profile and high efficacy of LDAA in IBD. It presents 2 advances in therapy: prescribing LDAA for thiopurine-naive patients, and bypassing TGN monitoring in favor of clinical monitoring (blood counts, etc.), which will make it more accessible for clinics without access to TGN assays.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Antimetabolites; Azathioprine; Blood Sedimentation; C-Reactive Protein; Chemical and Drug Induced Liver Injury; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Immunosuppressive Agents; Intestinal Mucosa; Male; Methyltransferases; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

The aim of this study was to evaluate and compare the clinical characteristics of the B-cell non-Hodgkin lymphoma (NHL) patients and therapeutic efficacy of modified NHL BFM-90 and NHL BFM-95 protocols in the authors' center. From January 1993 to December 2003, 61 newly diagnosed children with B-NHL were enrolled to the study. The patients were stratified by risk factors and treated either with a modified B-NHL BFM-90 or BFM-95 protocols. The use of 1 or 3 g/m2 of methotrexate instead of 5 g/m2/24 h was the only important modification in BFM-90 protocol. Sixty-one children (12 girls, 49 boys) with a median age of 6.5 years (range: 2.5-16) were treated in the center. There were 14 patients in stage II, 28 in stage III, and 19 in stage IV. The most common initial primary tumor sites were abdomen, head, and neck. Forty-five patients were treated with modified B-cell BFM-90 and 16 patients were treated with B-cell BFM-95 regimens. The 5-year overall survival (OS) for all patients was 85.8%, and event-free survival (EFS) was 82.8%. The 5-year OS rates in modified BFM-90 and in BFM-95 protocols were 85.2 and 87.5%; the 5-year EFS rates in these 2 protocols were 84.6 and 70%, respectively (p >.05). Factors associated with lower EFS by univariate analysis were bulky disease, risk groups, and LDH level > or = 500 IU/L. By multivariate analysis only LDH level was significant. In conclusion, the treatment results in this study were similar to those of BFM group.

Topics: Adolescent; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Diuretics; Female; Fluid Therapy; Hematologic Diseases; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Leucovorin; Lymphoma, B-Cell; Male; Methotrexate; Mucositis; Neoplasm Proteins; Risk Assessment; Sodium Bicarbonate; Survival Analysis; Survival Rate; Treatment Outcome; Tumor Burden; Tumor Lysis Syndrome; Turkey; Vincristine

Topics: Aged; Allopurinol; Azathioprine; Drug Interactions; Hematologic Diseases; Humans; Male; Middle Aged

Allopurinol has been shown to ameliorate the myelotoxicity of 5-fluorouracil (5-FU) given as an infusion. To study the potential effectiveness of allopurinol in modifying the toxicity of 5-FU given as a bolus, 8 adult patients with metastatic malignancies were given 11 courses of bolus 5-FU with allopurinol. Allopurinol was administered at a dose of 900 mg/day orally beginning a week prior to the 5-FU therapy and continued a week after the last dose of 5-FU was administered. Three patients received a total of 5 courses of 600 mg/m2 of 5-FU via bolus injection for 4 consecutive days every 28 days. Six patients were given 6 courses of 800 mg/m2 of 5-FU via bolus injection in the same schedule. Gastrointestinal toxicity was mild and no significant neurotoxicity was documented. However, severe myelosuppression occurred at the 800 mg/m2 dosage which led to marked leukopenia in 5 of the 6 patient courses and thrombocytopenia in 1. Gram-negative sepsis developed in 3 of the leukopenic patients with 2 resultant deaths. Allopurinol does not appear to allow clinically significant dose escalation of bolus 5-FU given on this schedule.

Topics: Adenocarcinoma; Adult; Allopurinol; Carcinoma, Squamous Cell; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Gallbladder Neoplasms; Gastrointestinal Diseases; Hematologic Diseases; Humans; Lung Neoplasms; Neoplasm Metastasis; Rectal Neoplasms

Azathioprine toxicity was examined in 64 consecutively treated patients with various neuromuscular diseases. Reversible leukopenia was seen in 14 patients (22%). Hepatotoxicity developed in six patients (9%), and a systemic reaction characterized by fever, abdominal pain, nausea, vomiting, and anorexia occurred in eight patients (12%). Toxic effects limited the dose of azathioprine in 27 patients (42%) and led to discontinuation of therapy in 13 (20%). Macrocytosis developed in 20% of patients, but did not require an adjustment in the dose. Two patients received allopurinol and azathioprine; both developed reversible leukopenia and macrocytosis. Patients with hematologic and hepatic toxicity, but not those with systemic toxicity, successfully tolerated retreatment with azathioprine. Toxicity was delayed as long as 56 weeks after starting azathioprine in some patients.

Topics: Allopurinol; Azathioprine; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Leukopenia; Liver; Male; Neuromuscular Diseases; Time Factors

Considerable interest has developed in the modulation of fluorouracil activity by nucleosides. The toxicity of fluorouracil in mice is known to be reduced by concurrent administration of allopurinol, presumably because biochemical pathways activating fluorouracil in normal tissues are blocked. We have given allopurinol (300 mg t.d.s. PO) concurrently with continuous infusions of fluorouracil (2.0--2.25 g/m2/day X 5) to 34 patients with colorectal cancer and 11 patients with various adenocarcinomas. There were 41 patients assessable for toxicity. Stomatitis was the predominant dose-limiting toxicity (22% grade 1, 19% grade 2, and 27% grade 3 toxicity). Neutropenia (Less Than 1,000/mu l) occurred in 17% patients. Among 26 colorectal cancer patients assessable for response there was a 15.4% response rate. We conclude that allopurinol modulates fluorouracil toxicity in man, allowing a two-fold increase in dose. However, at least in colorectal cancer no greater frequency of tumour response is seen than with lower doses of fluorouracil given by standard schedules of administration without allopurinol.

Topics: Allopurinol; Drug Eruptions; Drug Therapy, Combination; Fluorouracil; Hematologic Diseases; Humans; Neoplasms; Nervous System Diseases; Orotidine-5'-Phosphate Decarboxylase; Stomatitis

Of 29 524 hospitalised medical patients monitored in a drug surveillance programme 1835 (6.2%) received the xanthine oxidase inhibitor allopurinol. After the exclusion of skin reactions adverse effects were attributed to this drug in 33 (1.8%) patients, the most frequent being haematological abnormalities (11 patients, 0.6%) and diarrhoea and drug fever (5 each, 0.3%). Adverse effects were dose-related. Reactions were unrelated to age, weight, reason for therapy, admission blood urea, or albumin concentrations. Acute exacerbation of gout was troublesome in 3 patients (1 in 600 exposed).

Topics: Aged; Allopurinol; Diarrhea; Dose-Response Relationship, Drug; Female; Fever; Hematologic Diseases; Humans; Male; Middle Aged

Topics: Allopurinol; Gout; Hematologic Diseases; Humans; Kidney Diseases; Uric Acid

Topics: Allopurinol; Animals; Chemical and Drug Induced Liver Injury; Drug Eruptions; Gastrointestinal Diseases; Haplorhini; Hematologic Diseases; Humans; Kidney Diseases; Muscular Diseases; Neuritis

Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Aged; Allopurinol; Child; Diet Therapy; Female; Femur Head; Femur Head Necrosis; Hematologic Diseases; Humans; Hyperlipidemias; Lipids; Liver Diseases; Male; Metabolic Diseases; Middle Aged; Phospholipids; Uric Acid

Topics: Allopurinol; Clopamide; Enzyme Therapy; Gout; Hematologic Diseases; Humans; Hypertension; Kidney Failure, Chronic; Polythiazide; Uric Acid; Xanthine Oxidase

Topics: Adult; Allopurinol; Hematologic Diseases; Humans; Male; Middle Aged; Uric Acid