allopurinol and Bone-Marrow-Diseases

Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP.. Patients in maintenance were considered for allopurinol treatment who had the following features: (a) Grade ≥3 hepatotoxicity; (b) Grade ≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy.. From 2013 to 2017, 13 ALL patients received allopurinol: nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events. Allopurinol resulted in a significant decrease in the average 6MMP/6TGN ratio (mean reduction 89.1, P = .0001), with a significant increase in 6TGN (mean 550.4, P = .0008) and a significant decrease in 6MMP (mean 13 755, P = .0013). Patients with hepatotoxicity had a significant decrease in transaminase elevation after starting allopurinol (alanine transaminase [ALT] mean decrease 22.1%, P = .02), and all with nonhepatic GI toxicity had improved symptoms. Those with inadequate myelosuppression had a significant increase in the time with ANC in goal (mean increase 26.4%, P = .0004).. Allopurinol during ALL maintenance chemotherapy is a safe, feasible, and effective intervention for those who have altered metabolism of 6MP causing toxicity or inadequate myelosuppression.

Topics: Allopurinol; Antimetabolites; Bone Marrow Diseases; Child; Child, Preschool; Female; Follow-Up Studies; Gastrointestinal Diseases; Humans; Infant; Male; Mercaptopurine; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Retrospective Studies; Survival Rate

Low-dose thiopurine-allopurinol (LDTA) combination therapy is a commonly applied optimisation strategy in IBD patients with a skewed thiopurine metabolism.. To assess continued LDTA maintenance treatment at annual intervals and explore risk factors for treatment cessation METHODS: Adult IBD patients treated with LDTA between 2009 and 2016 were retrospectively included. Data on the incidence of clinical and laboratory adverse events (AEs), including hepatotoxicity and myelotoxicity resulting in imposing LDTA therapy cessation and associated risk factors were collected.. In total, 221 IBD patients (46% male, median age 42 years) were included. Maintenance LDTA treatment was continued in 78% of patients at 1 year (n = 145), 66% at 2 years (n = 83), 57% at 3 years (n = 52) and 52% at 4 years (n = 33). Treatment in patients receiving LDTA therapy for AEs during thiopurine monotherapy was more often continued than in patients initiating LDTA for other indications (eg, ineffectiveness of thiopurine monotherapy, routinely discovered skewed metabolism) (P = 0.016). Myelotoxicity during thiopurine monotherapy resolved in 87% and hepatotoxicity in 86% after median of 1.2 and 1.4 months after LDTA initiation. Cumulative incidence of AEs during LDTA resulting in therapy cessation within total follow-up of 449 treatment-years was 7% for clinical AEs, 4% for myelotoxicity and 1% for hepatotoxicity.. LDTA therapy is a safe and beneficial optimisation strategy in IBD patients. Continued maintenance LDTA treatment is 52% after 4 years of treatment and most commonly affected by ineffectiveness of LDTA rather than LDTA-attributed toxicity. LDTA optimisation strategy is most advantageous in patients failing thiopurine monotherapy due to AEs.

Topics: Adult; Allopurinol; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Medication Adherence; Mercaptopurine; Middle Aged; Netherlands; Retrospective Studies; Withholding Treatment

Topics: Aged; Allopurinol; Azathioprine; Biotransformation; Bone Marrow Diseases; Crohn Disease; Drug Interactions; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methyltransferases; Xanthine Oxidase

Topics: Adult; Allopurinol; Bone Marrow Diseases; Gout; Humans; Kidney Failure, Chronic; Male

We report the association of leucopenia and anaemia in five patients given a combination of azathioprine and allopurinol. Three subjects were renal transplant recipients with mild to moderate impairment of graft function. The complication appeared between 4 and 6 weeks following initiation of the combination therapy. Discontinuation of one of the two drugs resulted in full recovery within 4-8 weeks.

Topics: Adolescent; Adult; Allopurinol; Azathioprine; Bone Marrow Diseases; Drug Interactions; Female; Humans; Kidney Transplantation; Leukocyte Count; Male; Middle Aged; Platelet Count

Two renal transplant recipients with reversible bone marrow damage in the course of a simultaneous azathioprine-allopurinol therapy are discussed. Anemia, leukocytopenia and thrombocytopenia were found in both patients. Discontinuation of the azathioprine-allopurinol treatment was followed by increase of hematocrit, hemoglobin, erythrocytes, white blood cells and platelets. Interaction of azathioprine and allopurinol seems to be responsible for bone marrow damage in these patients. It can be concluded that the dose of azathioprine should be reduced when allopurinol is given concomitantly.

Topics: Adult; Allopurinol; Azathioprine; Bone Marrow Diseases; Drug Therapy, Combination; Female; Humans

Topics: Abdominal Neoplasms; Adolescent; Age Factors; Allopurinol; Antigens, Viral; Arabia; Bone Marrow Diseases; Brain Neoplasms; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Ethnicity; Female; Herpesvirus 4, Human; Humans; Israel; Jaw Neoplasms; Lymphoma, Non-Hodgkin; Male; Methotrexate; Prednisone; Vincristine

Topics: Allopurinol; Antineoplastic Agents; Bone Marrow Diseases; Cyclophosphamide; Drug Therapy, Combination; Humans

Topics: Aged; Allopurinol; Ampicillin; Anemia; Bone Marrow Cells; Bone Marrow Diseases; Bone Marrow Examination; Drug Hypersensitivity; Eosinophils; Female; Fibroblasts; Histiocytes; Humans; Lymphoid Tissue; Male; Mast Cells; Middle Aged; Plasma Cells; Procainamide

Topics: Allopurinol; Azathioprine; Blood Cell Count; Bone Marrow; Bone Marrow Diseases; Drug Interactions; Humans; Hypertension; Kidney Diseases; Male; Middle Aged

Topics: Allopurinol; Bone Marrow Diseases; Gout; Hodgkin Disease; Humans; Leukemia; Leukemia, Myeloid; Plasmacytoma; Polycythemia Vera; Uric Acid

Topics: Allopurinol; Bone Marrow Diseases; Drug Synergism; Enzyme Therapy; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Myeloproliferative Disorders; Xanthine Oxidase

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Blood; Bone Marrow Diseases; Child, Preschool; Colonic Neoplasms; Enzyme Therapy; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Mycosis Fungoides; Polycythemia Vera; Pyrimidines; Sarcoma; Uric Acid; Urinary Calculi; Xanthine Oxidase

Topics: Allopurinol; Arthritis; Blood; Bone Marrow Diseases; Drug Therapy; Enzyme Inhibitors; Fluids and Secretions; Gout; Humans; Metabolism; Pharmacology; Polycythemia Vera; Pyrazoles; Pyrimidines; Toxicology; Uric Acid; Uricosuric Agents; Urinary Calculi; Urine; Xanthine Oxidase