mercaptopurine and Sepsis

Preoperative immunosuppressive use among patients with Crohn's disease or ulcerative colitis may lead to an increased risk of postoperative complications. There is limited information on the preoperative safety profile of methotrexate (MTX) in inflammatory bowel disease (IBD).. A retrospective study of patients who underwent abdominal surgery for IBD between 1993 and 2012 was performed and records abstracted, including preoperative use of MTX, azathioprine/6-mercaptopurine, antitumor necrosis factor, and corticosteroids. Early postoperative complications, including death, septic, and nonseptic complications were identified. A meta-analysis was also performed on the use of preoperative MTX in patients with IBD or rheumatoid arthritis.. A total of 180 patients with IBD underwent abdominal surgery. A total of 15 patients received MTX either monotherapy or in combination therapy. Total early postoperative complications were identified in 71 (39%) patients, specifically 5 patients on oral MTX. A total of 51 cases (28%) of septic complications and 20 (11%) nonseptic. No significant association between the use of MTX and early postoperative complications was found. The odds ratio (OR) of complications versus no complications associated with MTX was 0.75 (95% CI, 0.25-2.29) and with azathioprine/6-mercaptopurine, OR 1.48 (95% CI, 0.77-2.84). The odds of a septic complication associated with MTX were 0.58 (95% CI, 0.09-3.73), and higher in azathioprine/6-mercaptopurine, OR 3.97 (95% CI, 1.03-15.3). Our meta-analysis also did not reveal an increased risk of postoperative complications in IBD or rheumatoid arthritis on preoperative MTX (OR 0.62, 95% CI, 0.34-1.15).. Preoperative MTX use does not seem to be associated with early postoperative complications in IBD.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Azathioprine; Colitis, Ulcerative; Crohn Disease; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Middle Aged; Odds Ratio; Postoperative Complications; Preoperative Period; Retrospective Studies; Sepsis; Tumor Necrosis Factor-alpha; Young Adult

Although thiopurine is a crucial drug for treating acute lymphoblastic leukemia, individual variations in intolerance are observed due to gene polymorphisms. A 3-year-old boy with B-cell precursor acute lymphoblastic leukemia who was administered thiopurine developed mucositis, sepsis, and hemophagocytic lymphohistiocytosis due to prolonged hematologic toxicity, chronic disseminated candidiasis, and infective endocarditis that triggered multiple brain infarctions. The patient was found to harbor 3 gene polymorphisms associated with thiopurine intolerance including homozygous NUDT15 R139C, heterozygous ITPA C94A, and homozygous MTHFR C677T and heterozygous RFC1 G80A. Thus, the combined effect of intolerance via multiple gene polymorphisms should be considered in case of unexpected adverse reactions.

Topics: Antimetabolites, Antineoplastic; Brain Infarction; Child, Preschool; Drug Hypersensitivity; Homozygote; Humans; Infections; Lymphohistiocytosis, Hemophagocytic; Male; Mercaptopurine; Mucositis; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Pyrophosphatases; Sepsis

BACKGROUND Pancytopenia is a hematological condition which is characterized by decreases in all three cellular elements: RBC, WBC, and platelets. As a result, patients with pancytopenia are more prone to anemia, infections, and excessive bleeding. Pancytopenia can be caused by medications or drug interactions that suppress the bone marrow. This case report highlights a drug interaction between allopurinol and mercaptopurine which led to pancytopenia and septic infection, resulting in the patient's death. This could easily have been avoided if a clinical pharmacist had been consulted. CASE REPORT A 55-year-old female patient with a past medical history of gout, depression, back pain, and type 2 diabetes was recently diagnosed with ulcerative colitis and was discharged with a new prescription of mercaptopurine. After 2 months of concurrent use of allopurinol and mercaptopurine, she developed infected foot ulcers, which progressed rabidly to sepsis. At the time, her laboratory findings confirmed pancytopenia. Despite treatment, the patient died. CONCLUSIONS This case illustrates the importance of consulting a clinical pharmacist in order to avoid such medical error. The dose of mercaptopurine should be reduced to 25% of the recommended dose when it is given concurrently with allopurinol to reduce the risk of pancytopenia. Health care providers should think about the significant role of clinical pharmacy services. In our case, there were no clinical pharmacist involved in the care of this patient, and as a result of such negligence, the patient lost her life.

Topics: Allopurinol; Colitis, Ulcerative; Diabetic Foot; Drug Interactions; Fatal Outcome; Female; Gout; Gout Suppressants; Humans; Immunosuppressive Agents; Mercaptopurine; Middle Aged; Pancytopenia; Pharmacists; Pharmacy Service, Hospital; Referral and Consultation; Sepsis

We report the diagnostic and therapeutic challenges in an unusually fulminant presentation of measles, presenting as severe necrotizing bronchiolitis with secondary hemophagocytic lymphohistiocytosis (HLH) in the absence of classical clinical features in an immunocompromised host on maintenance chemotherapy. Our patient had presented with features of a viral pneumonitis without the classical exanthem, in combination with HLH. Although rhinovirus-induced HLH was highly unusual, the positive rhinovirus swab result had distracted us from the eventual diagnosis. This calls for greater impetus to increase awareness and public education to improve vaccination rates and herd immunity to curb outbreaks and protect the immunocompromised patients.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Cryptogenic Organizing Pneumonia; Diagnostic Errors; Extracorporeal Membrane Oxygenation; Fatal Outcome; Humans; Lymphohistiocytosis, Hemophagocytic; Maintenance Chemotherapy; Male; Measles; Mercaptopurine; Methotrexate; Multiple Organ Failure; Pancytopenia; Picornaviridae Infections; Plasma Exchange; Pneumonia, Viral; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rhinovirus; Sepsis; Survivors

Lymphoma can rarely present as an ovarian tumor in children. We describe the unusual case of a 14-year-old adolescent with a locally disseminated ovarian anaplastic large-cell lymphoma, treated with surgery followed by chemotherapy, and who remains disease free at 2 years after diagnosis.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Female; Humans; Long QT Syndrome; Lymph Node Excision; Lymphoma, Large-Cell, Anaplastic; Mercaptopurine; Methotrexate; Omentum; Ovarian Neoplasms; Ovariectomy; Postoperative Complications; Prednisone; Remission Induction; Sepsis; Tumor Lysis Syndrome; Vincristine

Thiopurine methyltransferase (TPMT) is the main enzyme responsible for inactivating toxic products of azathioprine (AZA) metabolism. Patients with homozygous deficiency of this enzyme have no enzyme activity and ideally should not be given AZA. Patients with heterozygous deficiency have 50% of enzyme activity and have been shown to respond well and tolerate half a standard dose. We describe a patient with homozygous deficiency of TPMT who developed life threatening neutropenic sepsis, and advocate that all patients should be tested for TPMT activity prior to starting AZA therapy.

Topics: Aged; Arthritis, Rheumatoid; Azathioprine; Bone Marrow Diseases; Diagnostic Tests, Routine; Female; Homozygote; Humans; Immunosuppressive Agents; Inactivation, Metabolic; Mercaptopurine; Methylation; Methyltransferases; Neutropenia; Prodrugs; Sepsis; United Kingdom

We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia.

Topics: Aclarubicin; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 20; Combined Modality Therapy; Cytarabine; Disease Progression; Fatal Outcome; Female; Hemorrhage; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Monocytic, Acute; Mercaptopurine; Middle Aged; Neoplasm Proteins; Nuclear Pore Complex Proteins; Prednisolone; Sepsis; Translocation, Genetic

Topics: Antimetabolites, Antineoplastic; Burkitt Lymphoma; Child; Humans; Male; Mercaptopurine; Methotrexate; Piperacillin; Pseudomonas Infections; Seizures; Sepsis; Staphylococcal Infections

Intensive induction chemotherapy was applied to 25 patients with acute myelogenous leukemia by continuing drugs (daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone) until the achievement of severe bone marrow aplasia (leukemic cells less than 1,000/microliters). Complete remission (CR) was achieved in 18 (72%). Numbers of partial remission and an early death were 5 (20%) and 2 (8%), respectively. Although median nadirs of white blood cells (WBC) and platelet counts (Pl) (205/microliters and 8,200/microliters, respectively) were remarkably low, recovery of WBC (over 1,000/microliters) and Pl (over 50,000/microliters) were achieved in 23.8 and 24.5 days, after an initiation of the chemotherapy. Sepsis was a most frequently observed complication during induction stage and a duration of fever was 2-48 days (median 15). Median duration of CR was 22.9 months. Unexpectedly, 11 of 17 CR (except one with bone marrow transplanted) relapsed after 4.2-41.4 months (median; 9.4), but 6 (35.3%) still remain in first CR for 30.5-72.9 months (median; 51.4). A long-term survival might be obtained by intensifying induction chemotherapy in about one fourth of patients, but the intensification or application of non-cross resistant anti-leukemic agents in post-remission therapy may be required to avoid relapses even if induction is intensified.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission Induction; Sepsis; Survival Rate

Topics: Adolescent; Agranulocytosis; Candida; Child; Child, Preschool; Enterocolitis, Pseudomembranous; Escherichia coli; Female; Fever; Humans; Infant; Infections; Leukemia; Male; Mercaptopurine; Methotrexate; Mycoses; Pneumonia; Prednisone; Pseudomonas aeruginosa; Remission, Spontaneous; Sepsis; Staphylococcus; Time Factors; Vincristine

Topics: Adrenocorticotropic Hormone; Adult; Antimetabolites; Coal Tar; Dermatitis, Exfoliative; Glucocorticoids; Humans; Hydrocortisone; Male; Mercaptopurine; Methotrexate; Mouth Diseases; Oral Manifestations; Prednisolone; Psoriasis; Sepsis; Skin Diseases; Ulcer

Topics: Adolescent; Adult; Aged; Anemia; Blood Platelets; Blood Transfusion; Blood Urea Nitrogen; Bone Marrow Cells; Bone Marrow Examination; Chromosome Aberrations; Cytomegalovirus; Female; Fever; Hemorrhage; Humans; Jaundice; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Leukopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Nocardia Infections; Pneumonia; Prednisone; Proteus Infections; Pseudomonas Infections; Sepsis; Thrombocytopenia; Vincristine

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Aspartate Aminotransferases; Bacteroides; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Enterococcus faecalis; Female; Humans; Hyperbilirubinemia; Jaundice; Liver; Liver Diseases; Liver Function Tests; Male; Mercaptopurine; Postoperative Complications; Pseudomonas; Sepsis; Staphylococcus; Streptococcus; Tetracycline; Transfusion Reaction

Topics: Aeromonas; Child; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Osteomyelitis; Penicillin Resistance; Penicillins; Sepsis; Tetracycline

Topics: Acute Disease; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Agranulocytosis; Aspergillosis; Candidiasis; Cytarabine; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Mucormycosis; Nocardia Infections; Prednisone; Proteus Infections; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Strongyloidiasis; Uracil; Vinblastine

Topics: Adolescent; Aeromonas; Cyclophosphamide; Cytarabine; Female; Humans; Immunosuppressive Agents; Joint Diseases; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Sepsis; Vincristine

Topics: Acetazolamide; Adolescent; Amphotericin B; Candidiasis; Humans; Infectious Mononucleosis; Kidney Diseases; Leukemia; Male; Mercaptopurine; Methotrexate; Nystatin; Penicillins; Peripheral Nervous System Diseases; Prednisone; Rolitetracycline; Sepsis; Uric Acid

Topics: Adolescent; Appendicitis; Child; Child, Preschool; Escherichia coli Infections; Female; Humans; Leukemia; Male; Mercaptopurine; Mortality; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Blood Cell Count; Bone Marrow Examination; Candidiasis; Erythema Nodosum; Female; Gastrointestinal Hemorrhage; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisone; Sepsis

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antimetabolites; Antineoplastic Agents; Blood Transfusion; Cerebral Hemorrhage; Child; Hemorrhagic Disorders; Humans; Infant; Leukemia; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Photomicrography; Sepsis; Toxicology; Vitamins