mercaptopurine and Fever

This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2) per day if they did not develop myelotoxicity within 2 weeks after HDM. 6MP could be increased in 31 patients (81%). Toxicity was acceptable and did not differ significantly between groups. Patients receiving 75 mg/m(2) per day had significantly shorter duration of treatment interruptions of 6MP than the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Fever; Humans; Infant; Male; Mercaptopurine; Methotrexate; Mucositis; Pancreatitis; Pilot Projects; Precision Medicine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

Although cure rates in pediatric acute lymphoblastic leukemia (ALL) are quite high with combined chemotherapy regimens, complete response (CR) and long-term survival rates in adults are 80-90 and 30-40%, respectively. Currently, combined chemotherapy regimens, such as Hyper-CVAD and PETHEMA, are used in patients with adult ALL. However, there has been no study comparing the results of Hyper-CVAD and PETHEMA ALL-93.. In this retrospective single-center study, we evaluated the results of Hyper-CVAD and PETHEMA ALL-93 in 51 ALL patients treated between September 2008 and March 2017 at the Department of Hematology, Faculty of Medicine, Karadeniz Technical University.. Thirty-eight patients were treated with Hyper-CVAD and 13 with PETHEMA ALL-93. CR was obtained in 90 and 100% of patients, respectively. Survival estimates were comparable between Hyper-CVAD and PE-THEMA ALL-93, with a median overall survival (OS) and a median disease-free survival (DFS) of 17.5 and 12.1 months, respectively, for Hyper-CVAD and of 18.6 and 12.9 months, respectively, for PETHEMA ALL-93. The 2-year OS rates for Hyper-CVAD and PETHEMA ALL-93 were 30 and 40%, respectively, and the 2-year DFS rates were 28 and 44%, respectively. PETHEMA ALL-93 resulted in more hepatotoxicity, hypofibrinogenemia, aspergillus infection, and skin rash than Hyper-CVAD.. Although Hyper-CVAD and PE-THEMA ALL-93 showed similar effects, Hyper-CVAD was tolerated better. Age and comorbidities should be taken into account before a chemotherapy regimen is determined for patients with ALL.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacterial Infections; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Fever; Humans; Male; Mercaptopurine; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Retrospective Studies; Survival Rate; Treatment Outcome; Vincristine; Young Adult

Topics: Anti-Inflammatory Agents, Non-Steroidal; Atrial Fibrillation; Azathioprine; Cardiac Imaging Techniques; Colitis, Ulcerative; Fever; Heart Failure; Humans; Hypotension; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Mercaptopurine; Mesalamine; Middle Aged; Myocarditis

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Fever; Humans; Leukemia, Promyelocytic, Acute; Maintenance Chemotherapy; Male; Mercaptopurine; Methotrexate; Middle Aged; Recurrence; Tretinoin

To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well-defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH.. We conducted a retrospective study of all children who developed HLH over an 8-year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD.. Among children in Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in children with IBD. Common characteristics include: Crohn's disease (CD), thiopurine administration, fever lasting more than 5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin. Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was more than 100-fold greater for children with CD (P < .00001).. Pediatric patients with CD are at increased risk for developing HLH; primary Epstein-Barr virus infection and thiopurine administration may be risk factors.

Topics: Adolescent; Anemia; Azathioprine; Crohn Disease; Epstein-Barr Virus Infections; Ferritins; Fever; Humans; Immunosuppressive Agents; Incidence; Lymphatic Diseases; Lymphohistiocytosis, Hemophagocytic; Lymphopenia; Mercaptopurine; Retrospective Studies; Splenomegaly; Triglycerides; Wisconsin

The antimetabolite mercaptopurine is commonly used as part of treatment regimens for acute lymphoblastic leukemia and as treatment for inflammatory bowel diseases. Adverse effects associated with mercaptopurine include myelosuppression, hepatotoxicity, and hyperpigmentation. We describe a 36-year-old man with Philadelphia chromosome-negative pre-B-cell acute lymphoblastic leukemia who experienced a serious mercaptopurine-induced hypersensitivity reaction requiring prolonged hospitalization and extensive laboratory testing and imaging. He was treated with a multiagent chemotherapy regimen. Mercaptopurine 60 mg/m(2)/day orally was started as part of his third course of chemotherapy. On day 9 of mercaptopurine therapy, the patient developed persistent fevers, skaking chills, and rigors that persisted in the absence of documented infection, consistent with drug fever. All symptoms and signs resolved after discontinuation of mercaptopurine. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of fever and mercaptopurine therapy. Mercaptopurine-induced fever has been reported in patients with inflammatory bowel diseases, but this case report is the first, to our knowledge, in a patient with acute lymphoblastic leukemia. Health care professionals should be aware of the possible development of fever as a hypersensitivity reaction in patients with acute lymphoblastic leukemia treated with mercaptopurine.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Hypersensitivity; Fever; Humans; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Bone Marrow; Bone Marrow Diseases; Fever; Humans; Hydroxyurea; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Middle Aged; Necrosis; Oxides; Pancytopenia; Remission Induction

Topics: Adult; Crohn Disease; Female; Fever; Humans; Immunosuppressive Agents; Leukopenia; Male; Mercaptopurine; Remission Induction; Severity of Illness Index; Time Factors

Topics: Adult; Drug Therapy, Combination; Female; Fever; Humans; Leukemia, Lymphoid; Mercaptopurine

After a chronic phase, the average duration of which in this series was 38 months, the acute phase of myeloid leukemia was very short, not exceeding 7 months. The clinical signs which suggest an acute exacerbation are, in order of importance, increase in the volume of the spleen, changes in general health, fever. The blood signs, which are often found later than the clinical signs, are increased white cell count, anemia and marrow leukoblastosis higher than 20%. The laboratory criteria of acute exacerbation are of lesser importance. Chemotherapy gives very poor results at this stage.

Topics: Alkaline Phosphatase; Female; Fever; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Splenomegaly

Topics: Adolescent; Adult; Aged; Busulfan; Chromosome Aberrations; Daunorubicin; Female; Fever; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisone; Splenomegaly; Time Factors

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: Adolescent; Adult; Aged; Allopurinol; Anaphylaxis; Asparaginase; Blood Coagulation Disorders; Cytarabine; Daunorubicin; Drug Hypersensitivity; Female; Fever; Gastrointestinal Hemorrhage; Hallucinations; Humans; Hyperglycemia; Injections, Intravenous; Jaundice; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Liver; Male; Mercaptopurine; Methotrexate; Middle Aged; Oral Hemorrhage; Prednisone; Thioguanine; Uremia; Vincristine; Vomiting

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: Chromatography; Chromatography, Gel; Drug Tolerance; Endotoxins; Escherichia coli Infections; Fever; Immunoelectrophoresis; Immunosuppressive Agents; Mercaptopurine; Rabbits; Research; Toxicology; Ultracentrifugation

Topics: Adenine; Antineoplastic Agents; Drug Therapy; Fever; Hematocrit; Leukemia; Leukocyte Count; Mercaptopurine; Purines; Thioguanine; Toxicology

Topics: Aminocaproates; Aminocaproic Acid; Anemia; Antineoplastic Agents; Blood Transfusion; Busulfan; Central Nervous System; Fever; Hemorrhage; Humans; Leukemia; Mechlorethamine; Mercaptopurine; Nervous System; Physiology; Prednisolone; Thiotepa; Vitamin K 1