mercaptopurine and Infections

Thiopurine agents have been shown to be effective in maintaining remission in patients with Crohn's disease. There is less evidence for the efficacy of these treatments in ulcerative colitis. Consequently, the effect of thiopurines in the latter disease continues to be the subject of debate and controversy remains on whether these drugs are equally effective in both diseases. The present article aims to review, from a practical point of view, the evidence of the efficacy of thiopurines in ulcerative colitis, current indications for this treatment, safety in patients with inflammatory bowel disease and the treatment optimization strategies proposed.

Topics: Azathioprine; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Disease Susceptibility; Dose-Response Relationship, Drug; Humans; Immunocompromised Host; Immunosuppressive Agents; Infections; Mercaptopurine; Meta-Analysis as Topic; Neoplasms; Prodrugs; Remission Induction; Treatment Outcome

The immunomodulators (6-mercaptopurine, azathioprine and methotrexate) and biologics (infliximab, adalimumab, certolizumab and natalizumab) are medications essential in the management of pediatric inflammatory bowel disease. If properly utilized, these medications can control active disease, reduce corticosteroid exposure, induce remission, and promote normal growth and development. However, these medications also have significant toxicity and increase the risk of infections and lymphoma. This article provides information about the safety and efficacy of these medications in the treatment of children with Crohn's disease and ulcerative colitis.

Topics: Antibodies, Monoclonal; Child; Colitis, Ulcerative; Crohn Disease; Humans; Immunologic Factors; Infections; Lymphoma; Mercaptopurine; Treatment Outcome

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.

Topics: Acute Kidney Injury; Anemia, Aplastic; Antilymphocyte Serum; Arthritis, Rheumatoid; Blood Cell Count; Blood Transfusion; Cyclophosphamide; Deficiency Diseases; Erythropoietin; Humans; Immune System Diseases; Infections; Lupus Erythematosus, Systemic; Mercaptopurine; Prednisone; Remission, Spontaneous; Splenectomy; Thymoma; Thymus Neoplasms

Current therapy has resulted in improved prognosis in previously untreated children with acute lymphocytic leukemia less than 16 years of age. The induction phase of chemotherapy should include the use of at least prednisone and vincristine. This combination should result in a hematologic remission in about 90 per cent of the patients. The efficacy of the addition of either L-asparaginase or daunomycin, the consolidation phase or the periodic readministration of induction drugs has not been established. Specific central nervous system treatment, early in the course of therapy, is an integral component of recently reported effective protocols. Several modalities of prophalytic central nervous system therapy have been utilized. These include cranial irradiation plus intrathecal methotrexate, craniospinal irradiation and intrathecal methotrexate alone. An encephalopathy syndrome has been reported as a complication in 10 to 66 per cent of these patients. The most effective form of central nervous system therapy, associated with the least toxicity, has not been established. Maintenance chemotherapy should include a combination of two or more drugs. Complications are numerous, and include hematopoietic depression, immunosuppression, overwhelming infections, and, possibly, the development of secondary primary cancers. In the most successful protocols maintenance chemotherapy has been administered for 3 years. Because of the potential significant toxicity there is a need to define the optimal duration of maintenance therapy. Psychological complications developing in a patient with a disease now considered a potential long term chronic illness, rather than a disease once considered universally fatal, are also discussed. The possibility of an immunologic deficiency allowing for the initial development of acute lymphocytic leukemia and the role of immunotherapy are presented. While the use of intensive combination chemotherapy and specific central nervous system prophylactic therapy have resulted in an improved prognosis in childhood acute lymphocytic leukemia, because of a significant incidence of failures, a standardized single form of therapy has not been established.

Topics: Asparaginase; Central Nervous System Diseases; Child; Cyclophosphamide; Daunorubicin; Drug Therapy, Combination; Humans; Immunotherapy; Infections; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Neoplasms, Multiple Primary; Prednisone; Psychology; Remission, Spontaneous; Vincristine

Topics: Adult; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Combinations; Hodgkin Disease; Humans; Immunotherapy; Infections; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Methotrexate; Middle Aged; Nitrogen Mustard Compounds; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Vincristine

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Chlorambucil; Colitis, Ulcerative; Crohn Disease; Cyclophosphamide; Granulomatosis with Polyangiitis; Hepatitis; Humans; Immune Complex Diseases; Immunosuppressive Agents; Infections; Liver Cirrhosis, Biliary; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Nephrotic Syndrome; Ophthalmia, Sympathetic; Psoriasis; Thioguanine; Uveitis

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Autoimmune Diseases; Azathioprine; Bone Diseases; Diabetes Mellitus; Drug Synergism; Duodenal Ulcer; Embolism, Fat; Glomerulonephritis; Histocompatibility; Humans; Hypertension, Renal; Immunosuppressive Agents; Infections; Kidney Glomerulus; Kidney Transplantation; Malabsorption Syndromes; Male; Mercaptopurine; Neoplasm Transplantation; Neoplasms; Obesity; Osteoporosis; Pancreatitis; Peptic Ulcer Hemorrhage; Phenylbutazone; Postoperative Complications; Proteinuria; Transplantation, Homologous

Shortly before the all-trans retinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m(2) IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m(2) IDA daily for 4 days combined with 200 mg/m(2) Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P =.0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P =.0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/microL (P =.0001) and increasing age (P =.0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL.

Topics: Adolescent; Adult; Age Factors; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Child; Cytarabine; Disease-Free Survival; Female; Follow-Up Studies; Hemorrhage; Humans; Idarubicin; Infections; Leukemia, Promyelocytic, Acute; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission Induction; Treatment Outcome; Vomiting

6-Mercaptopurine (6-MP) is metabolized by thiopurine S-methyltransferase (TPMT), an enzyme subject to genetic polymorphism. We investigated the relationships between the TPMT locus (TPMT activity and genotype) and the pharmacological response to 6-MP during maintenance therapy of 78 children with acute lymphoblastic leukemia (ALL). For each patient, 6-MP dosage, leukocyte counts and occurrence of infectious episodes were monitored on an 8 week basis. Higher 6-MP dosage was associated with higher TPMT activity (P = 0.03) and higher average leukocyte counts (P < 0.01). Eight patients (10%) carrying a TPMT mutant genotype (one homozygous and seven heterozygous) received lower 6-MP doses (average: 48 vs 65 mg/m2/day; P = 0.02) and had on average lower leukocyte counts (2834 vs 3398 cells/mm3; P = 0.003) than patients carrying the wild-type TPMT genotype. Higher occurrence of infectious episodes graded 2 or 3 was correlated with higher 6-MP dosage (P < 0.01) but no difference was observed between TPMT mutants and TPMT wild-type patients. Patients who received 6-MP dosage above the group median (62 mg/m2/day) or having a TPMT activity above the group median (21.5 nmol/h/ml) had a higher percentage of 8 week periods with infectious episodes requiring treatment (34% vs 17% and 33% vs 19%, respectively) than those with 6-MP dose or TPMT activity below the group median (P < 0.01). In the last 25 patients enrolled in the study, steady-state erythrocyte thioguanine nucleotide (TGN) concentrations were associated with lower leukocyte counts (P= 0.01) but not with a higher occurrence of infectious episodes. In contrast, higher steady-state erythrocyte methylmercaptopurine nucleotide (MeMPN) concentrations were associated with higher 6-MP dosage (P< 0.01) and higher occurrence of infectious episodes (P < 0.001). In conclusion, during maintenance therapy of ALL, children with higher TPMT activity receive a higher 6-MP dosage and may have infectious episodes caused by metabolism of 6-MP into methylmercaptopurine nucleotides.

Topics: Adolescent; Antimetabolites, Antineoplastic; Child; Child, Preschool; Dose-Response Relationship, Drug; Erythrocytes; Female; Genotype; Humans; Infant; Infections; Leukocyte Count; Male; Mercaptopurine; Methyltransferases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thioguanine

Four hundred thirty patients with high-risk acute lymphoid leukemia were entered on the acute leukemia in childhood protocol (AlinC 12) of the Pediatric Division of the Southwest Oncology Group (now the Pediatric Oncology Group) between 1976 and 1979. This study was a prospective randomized comparison of two regimens that had as their primary differences: (1) an intensification period with Cytoxan (cyclophosphamide) and asparaginase after induction; (2) a period of intravenous methotrexate before initiating maintenance; and (3) in the regimen that had those two additions, triple-drug chemoprophylaxis of the central nervous system (CNS) using methotrexate, hydrocortisone, and cytosine arabinoside as compared to cranial irradiation and intrathecal methotrexate. All patients received vincristine and prednisone induction, 6-mercaptopurine and methotrexate maintenance, and vincristine and prednisone pulse intensification. There was no significant difference in the rate of bone marrow relapse. However, overall disease-free survival favored the arm with intensification and chemoprophylaxis because of a lesser incidence of extramedullary relapse. Thus, for treatment 1 versus treatment 3 the two-sided P values were for overall disease-free survival 0.16; bone marrow relapses 0.13; all CNS relapses 0.04; and all extramedullary disease relapses 0.013. It is concluded that intensification as delivered in this protocol protects against testicular relapse and that chemoprophylaxis is adequate prophylaxis against isolated CNS relapse.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Humans; Hydrocortisone; Infant; Infant, Newborn; Infections; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prospective Studies; Random Allocation; Remission Induction; Vincristine

Topics: Adolescent; Adult; Blood Transfusion, Autologous; Brain Neoplasms; Child; Child, Preschool; Cobalt Isotopes; Cyclophosphamide; Female; Humans; Infant; Infections; Injections, Intravenous; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Radiation Dosage; Radiation Effects; Remission, Spontaneous; Spinal Cord Neoplasms; Time Factors

The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.. We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.. We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.. In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.

Topics: Adalimumab; Adult; Anti-Bacterial Agents; Autoimmune Diseases; Cesarean Section; Child Development; Child, Preschool; Congenital Abnormalities; Drug Prescriptions; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Infections; Inflammatory Bowel Diseases; Infliximab; Mercaptopurine; Neoplasms; Netherlands; Patient Admission; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Retrospective Studies; Tumor Necrosis Factor Inhibitors; Vaccines

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

The ENCORE registry aimed at comparing the long-term safety of Crohn's disease [CD] treatment with infliximab [Remicade®] and with conventional therapies in real-world clinical practice.. The 5-year, prospective, observational ENCORE registry followed patients with CD in nine European countries, who received treatment with infliximab, conventional therapies, or switched to infliximab from conventional therapy. Adverse events [AEs] in pre-specified categories and serious AEs were recorded at least every 6 months of the 5-year observation period. Frequency of events was evaluated, and multivariable analyses using follow-up time [Cox proportion hazards model] and exposure time [Poisson regression] were used to identify risk factors for time to AEs in pre-specified categories.. Patients who received infliximab [N = 1541], conventional therapies [N = 1121], or switched to infliximab [N = 298] were followed for medians of 60.4, 55.6, and 42.5 months, respectively. Infliximab median exposure was 18.7 and 19.3 months in the infliximab and switched-to-infliximab groups, respectively. In time-to-event Cox proportion hazards [PH] analyses adjusting for confounders, infliximab [vs conventional therapy] was associated with serious infections (hazard ratio [HR] = 1.64, 95% confidence interval [CI]: 1.17, 2.31] and haematological conditions [HR = 2.91, CI: 1.51, 5.59], and not associated with lymphoproliferative disorders/malignancy [HR = 1.44, CI: 0.86, 2.42] or death [HR = 1.22, CI: 0.63, 2.36]. Prednisone use was associated with higher mortality [HR = 3.58, CI: 1.49, 8.61]. In exposure-adjusted Poisson regression analyses, infliximab was associated with lower mortality (risk ratio [[RR] 0.39, CI: 0.17, 0.88]).. Data from 5-year safety follow-up of patients with CD in the ENCORE registry demonstrate that infliximab [Remicade®] exposure is associated with increased risk of serious infections and haematological conditions, whereas mortality may be decreased.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azathioprine; Crohn Disease; Demyelinating Diseases; Drug Substitution; Drug Therapy, Combination; Female; Gastrointestinal Agents; Hematologic Diseases; Humans; Immunosuppressive Agents; Infections; Infliximab; Infusions, Intravenous; Lymphoproliferative Disorders; Male; Mercaptopurine; Mesalamine; Methotrexate; Middle Aged; Mortality; Narcotics; Prednisone; Prospective Studies; Registries; Risk Factors; Sulfasalazine; Time Factors; Young Adult

Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment-related morbidity and mortality. Herein, we investigate how pretreatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive individuals receiving curative-intent induction chemotherapy with cytarabine and an anthracycline ("7 + 3"; n = 175) or a "7 + 3"-like regimen (n = 30). Among the entire cohort, baseline grade 4 neutropenia (i.e., absolute neutrophil count <500 cells/µL) was associated with development of fever (P = 0.04), documented infection (P < 0.0001), and bacteremia (P = 0.002) but not requirement for intensive care unit-level care; after exclusion of the 30 patients who received "7 + 3"-like induction, baseline grade 4 neutropenia remained associated with documented infection (P < 0.0001) and bacteremia (P = 0.0005). Among patients achieving a complete remission with the initial treatment cycle, grade 4 neutropenia was associated with delayed neutrophil count recovery (P < 0.0001). Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic/molecular risk, and performance status, the risk of fever, documented infection, or bacteremia was 1.87 (95% confidence interval: 1.04-3.34; P=0.04)-fold, 4.95 (2.20-11.16; P<0.001)-fold, and 3.14 (0.99-9.98; P=0.05)-fold higher in patients with initial grade 4 neutropenia. Together, our studies identify severe baseline neutropenia as a risk factor for infection-associated adverse events after induction chemotherapy and may provide the rationale for the risk-adapted testing of myeloid growth factor support in this high-risk AML/MDS patient subset.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Blood Cell Count; Critical Care; Cyclophosphamide; Cytarabine; Daunorubicin; Febrile Neutropenia; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunocompromised Host; Infections; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Proportional Hazards Models; Remission Induction; Retrospective Studies; Young Adult

Immunosuppression is a major side effect of cancer chemotherapy. The process of immune reconstitution can be dissimilar according to the nature of the disease, type and doses of drugs, and age of the patients. Recently, several studies have examined immune reconstitution in children and young adults after intensive chemotherapy for solid tumours or stem cell transplantation. The aim of the present study is to evaluate immune reconstitution (cellular and humoral) in children with acute lymphoblastic leukemia during the maintenance phase of therapy and to correlate between the complicating infections and the abnormalities in immune system during reconstitution. To achieve this goal, 36 children with acute lymphoblastic leukemia (24 females and 12 males) in the maintenance phase of therapy with 12 healthy children of matched age and sex served as a control group were recruited in this study. The patients were taken consecutively from the Hematology/Oncology Outpatient Clinic of Mansoura University Children's Hospital (MUCH). They were subjected to thorough history taking, clinical examination and laboratory investigations in the form of: complete blood count, serum creatinine, liver function tests and evaluation of the immune system by estimation of CD3, CD4, CD8, CD19 and CD56 (cellular immunity) by flow cytometry and immunoglobulins A, M and G (humoral immunity) at the first and the third month of maintenance therapy. The results of the study documented presence and persistence of leucopenia and lymphopenia during maintenance therapy with decreased medians of CD3, CD4 and CD8 from the first to the third month of therapy and in comparison to the control group. The other markers CD19, CD56, IgA, IgM, IgG and CD4/CD8 ratio showed increasing median from the first to the third month of therapy. Also we detect a significant correlation between infection and CD19 and serum IgM at the first month and between infection and CD19, IgM and CD4/CD8 ratio at the third month of therapy. In conclusion, persistent immunosuppression is documented in children with acute lymphoblastic leukemia during maintenance therapy. Reconstitution of B lymphocytes and Natural killer cells occurs early while T cell reconstitution shows delayed recovery of both T helper and T suppressor cells. Immunosupression during maintenance therapy has no major clinical impact in terms of increased incidence or severity of systemic infections.

Topics: Adolescent; Adrenal Cortex Hormones; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Case-Control Studies; CD4-CD8 Ratio; Child; Child, Preschool; Female; Humans; Immunoglobulins; Infections; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vincristine

The introduction of the United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline therapy has improved outcome of children with acute myeloid leukemia (AML). In this study, we review the results of childhood AML therapy in a Singapore university hospital over the last 17 years emphasizing toxicity and outcome.. Retrospective analysis revealed 34 children with AML between 1988 and 2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n = 9). From September 1996, all but one of 15 children received MRC AML 10 treatment.. At the time of analysis, 17 had died from disease, and 17 patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n = 14) had significantly better 3-year overall, event-free, and disease-free survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P = 0.010, respectively) and were likelier to achieve complete remission (CR) than non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10-treated patients were significantly more likely to achieve CR after only one cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the different regimens (P = 0.9).. These findings suggest that MRC AML 10 treatment results in significantly superior survival, without excess toxicity. Future studies should attempt to elucidate the relative importance of individual MRC AML 10 components and reduce the high cumulative anthracycline dose without compromising outcome.

Topics: Acute Disease; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cytarabine; Daunorubicin; Developing Countries; Disease-Free Survival; Drug Evaluation; Etoposide; Female; Gastrointestinal Diseases; Heart Diseases; Hematologic Diseases; Humans; Infant; Infections; Kaplan-Meier Estimate; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Mitoxantrone; Prednisone; Remission Induction; Retrospective Studies; Singapore; Survival Analysis; Thioguanine; Treatment Outcome; Vincristine

Many patients with inflammatory bowel disease receive corticosteroids and 6-mercaptopurine/azathioprine during elective bowel surgery. We investigated the postoperative infection risk for patients undergoing elective bowel surgery who were receiving corticosteroids and/or 6-mercaptopurine/azathioprine before surgery compared with patients not receiving these medications.. A retrospective cohort study was conducted on 159 patients with inflammatory bowel disease who underwent elective bowel surgery. There were 56 patients receiving corticosteroids alone, 52 patients receiving 6-mercaptopurine/azathioprine alone or with corticosteroids, and 51 patients receiving neither corticosteroids nor 6-mercaptopurine/azathioprine. Postoperative infectious complications to time of discharge were categorized into major and minor complications.. Patients receiving corticosteroids had an adjusted odds ratio for any and major infectious complications of 3.69 (95% confidence interval [CI], 1.24-10.97) and 5.54 (95% CI, 1.12-27.26), respectively. The adjusted odds ratio for patients receiving 6-mercaptopurine/azathioprine for any and major infectious complications was 1.68 (95% CI, 0.65-4.27) and 1.20 (95% CI, 0.37-3.94), respectively.. Preoperative use of corticosteroids in patients with inflammatory bowel disease who are undergoing elective bowel surgery is associated with an increased risk of postoperative infectious complications. 6-Mercaptopurine/azathioprine alone and the addition of 6-mercaptopurine/azathioprine for patients receiving corticosteroids was not found to significantly increase the risk of postoperative infectious complications.

Topics: Adjuvants, Immunologic; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Cohort Studies; Female; Humans; Infections; Inflammatory Bowel Diseases; Length of Stay; Male; Mercaptopurine; Middle Aged; Postoperative Complications; Retrospective Studies; Risk

Topics: Adjuvants, Immunologic; Azathioprine; Humans; Infections; Inflammatory Bowel Diseases; Mercaptopurine; Postoperative Complications

Burkitt's lymphoma is a rare aggressive lymphoma, which responds poorly to standard chemotherapy regimens used to treat high-grade non-Hodgkin's lymphoma (NHL). The use of intensive chemotherapy protocols using alkylating agents and intensive CNS prophylaxis has dramatically altered prognosis. We have treated eight patients with Burkitt's lymphoma with a modified BFM protocol. The dose of methotrexate was reduced from 5 g/m2 to 1.5 g/m2 with the aim of reducing toxicity. Seven patients received a total of six cycles of chemotherapy each and one patient received five cycles of chemotherapy. Each cycle included high-dose methotrexate, an alkylating agent (ifosphamide or cyclophosphamide) and two triple intrathecal injections of chemotherapy. Two patients with bulky abdominal disease in addition received an autologous stem cell transplant. The regimen was well tolerated with minimal toxicity. At a median follow-up of 16 months (range 10-28), six of the eight patients (75%) were alive and in complete remission. Two patients relapsed, one 24 months post-BFM chemotherapy and the other 1-month post-autologous stem cell transplantation and 2 months post-BFM chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Infections; Lymphoma, AIDS-Related; Male; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Remission Induction; Treatment Outcome; Vincristine

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are used in pediatric patients with ulcerative colitis and Crohn's disease to reduce disease activity, maintain remission, prevent relapse, and lower corticosteroid dosage, but their long-term side effects remain to be studied. The aim of this study was to analyze the safety of AZA and 6-MP and steroid reduction in this age group.. The investigators' database identified 118 patients who received either drug; 23 were excluded (single visit, noncompliance, or therapy < 1 week), leaving 95 patients, with a mean (+/-SD) age of 14.2 +/- 4.4 years. Medical files were reviewed for adverse side effects: fever, pancreatitis, infections, gastrointestinal intolerance, aminotransferase level increase, leukopenia, and thrombocytopenia. Prednisone doses before and after immunomodulatory therapy were compared.. AZA or 6-MP was tolerated in 51 of 95 patients (54%) without adverse reaction; 27 of 95 (28%) experienced side effects that responded to dose reduction (23 patients) or spontaneously (4 patients), most commonly increased aminotransferase level (13.7%). Cessation of therapy was needed in 17 of 95 patients (18%), including recurrent fever (4), pancreatitis (4), gastrointestinal intolerance (4), and recurrent infections (3). Mean prednisone dose decreased from 24.3 to 8.6 mg/day.. AZA and 6-MP were well tolerated in 82% of patients; of these, prednisone reduction occurred in 87%. However, 18% required discontinuation because of hypersensitivity or infectious side effects.

Topics: Adolescent; Adult; Azathioprine; Child; Child, Preschool; Databases as Topic; Drug Hypersensitivity; Humans; Immunosuppressive Agents; Infections; Inflammatory Bowel Diseases; Medical Records; Mercaptopurine; Prednisone

We assess toxicity related to 6-mercaptopurine in the treatment of inflammatory bowel disease by reporting our experience with 396 patients (120 patients with ulcerative colitis, 276 with Crohn disease) observed over 18 years. Follow-up data for a mean period of 60.3 months were obtained for 90% of the patients. Toxicity directly induced by 6-mercaptopurine included pancreatitis in 13 patients (3.3%), bone marrow depression in 8 (2%), allergic reactions in 8 (2%), and drug hepatitis in 1 (0.3%). These complications were reversible in all cases with no mortality. Most cases of marrow depression occurred earlier in our experience, when the initial drug doses used were higher. Infectious complications were seen in 29 patients (7.4%), of which 7 (1.8%) were severe, including one instance of herpes zoster encephalitis. All infections were reversible with no deaths. Twelve neoplasms (3.1%) were observed, but only 1 (0.3%), a diffuse histiocytic lymphoma of the brain, had a probable association with the use of 6-mercaptopurine. Our data, showing a low incidence of toxicity in 396 patients, coupled with the previously demonstrated efficacy of 6-mercaptopurine in the treatment of inflammatory bowel disease, indicate that the drug is a reasonable alternative in the management of patients with intractable inflammatory bowel disease.

Topics: Adolescent; Adult; Aged; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Child; Colitis, Ulcerative; Crohn Disease; Double-Blind Method; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Infections; Male; Mercaptopurine; Middle Aged; Neoplasms; Pancreatitis; Pregnancy; Time Factors

A 34% response was obtained in 202 evaluable patients in the terminal phase of chronic granulocytic leukemia using combinations of hydroxyurea, 6-mercaptopurine, and corticosteroids. Twelve percent of responses were complete and 22% partial. Overall median survival was 12 wk. A 30 wk median survival for responding patients was statistically superior to the 7-wk survival for nonresponders (p less than 0.001). Response was inversely correlated with toxicity. No responses were obtained in patients sustaining both severe infectious and bleeding complications. No benefit could be demonstrated from the addition of vincristine in induction and daunorubicin for consolidation. Although the response frequency and duration of survival with this combination chemotherapy were generally superior to those previously reported by our group, the terminal phase of chronic granulocytic leukemia still remains a formidable and generally refractory disease.

Topics: Daunorubicin; Dexamethasone; Drug Therapy, Combination; Gastrointestinal Diseases; Hemorrhage; Humans; Hydroxyurea; Infections; Leukemia, Myeloid; Mercaptopurine; Prednisone; Remission, Spontaneous; Terminal Care

In 40 children suffering from a form of chronic juvenile arthritis (CJA), the authors found encouraging results after immuno-suppressive treatment. Indeed, major corticotherapy, often necessary in these forms, could be stopped in nearly half the cases. The immediate improvement in the clinical signs of the disease was very clear and the signs of corticoid intoxication regressed, and in particular growth was normally resumed in many of the children. While the immediate infectious and hematologic consequences are generally benign, the occurrence of malignant hemopathies at a distance, seen in 3 cases, mean that use of this type of therapy should be totally reconsidered during CJA. The authors feel that because of this grave oncogenic risk, the immunosuppressive treatments should not be reserved merely for forms that involves the vital prognosis in the more or less short run.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Arthritis, Juvenile; Child; Child, Preschool; Chlorambucil; Female; Follow-Up Studies; Genital Diseases, Male; Hematologic Diseases; Humans; Immunosuppressive Agents; Infections; Male; Mercaptopurine; Risk; Time Factors

Topics: Abnormalities, Drug-Induced; Azathioprine; Cortisone; Cyclophosphamide; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Infertility; Male; Mercaptopurine; Methotrexate; Neoplasms; T-Lymphocytes

Infections in the immunosuppressed cancer patient are caused by a wide variety of bacteria, viruses, fungi, and protozoa; many of these in the normal individual are saprophytes but will cause disease in the immunosuppressed patient, often with treatment failure. Patterns of infection are recognized, and this should enable the physician to plan a meaningful course of action when infection occurs in the compromised host. Obviously, it would be much better to prevent rather than have to treat infection in these immunosuppressed patients. Ideally, in the future, it is hoped that drugs which have less suppressive effect on defense mechanisms will provide a partial solution to the problem of infection in the immunosuppressed patient.

Topics: Adrenal Cortex Hormones; Alkylating Agents; Antineoplastic Agents; Azathioprine; Bacteria; Bacterial Infections; Folic Acid Antagonists; Humans; Immunity, Cellular; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Lymphocytes; Mercaptopurine; Mycoses; Neoplasms; Phagocytosis; Protozoan Infections; Virus Diseases

Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; Autopsy; Azathioprine; Brain; Breast Neoplasms; Female; Hodgkin Disease; Humans; Immunosuppression Therapy; Infection Control; Infections; Kidney Transplantation; Lung; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Middle Aged; Myocardium; Neoplasm Metastasis; Prednisone; Toxoplasmosis; Transplantation, Homologous

Topics: Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Cystitis; Drug Therapy, Combination; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Infant; Infections; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia, Viral; Prednisone; Remission, Spontaneous; Skin Diseases; Vincristine; Viral Vaccines; Virus Diseases

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: Acute Disease; Adolescent; Agammaglobulinemia; Antibody Formation; Antineoplastic Agents; Blood Transfusion; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Immunosuppressive Agents; Infant; Infections; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Serum Albumin

Topics: Acute Disease; Adolescent; Adult; Aged; Azathioprine; Female; Humans; Infections; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous

Topics: Acute Disease; Adolescent; Adult; Aged; Azathioprine; Female; Humans; Infections; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous

Topics: Animals; Antineoplastic Agents; Asparaginase; Blood Platelets; Bone Marrow Cells; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Models, Animal; Drug Synergism; Hemorrhage; Humans; Infections; Leukemia L1210; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Mice; Prednisone; Prognosis; Thrombocytopenia; Vincristine

Topics: Aminopterin; Child; Child, Preschool; Diagnosis, Differential; Haptoglobins; Hematologic Diseases; Humans; Infant; Infections; Leukemia; Lymphoma; Mercaptopurine; Neuroblastoma; Prednisone

Topics: Animals; Busulfan; Chlorambucil; Cyclophosphamide; Dactinomycin; Drug-Related Side Effects and Adverse Reactions; Folic Acid Antagonists; Haplorhini; Hematologic Diseases; Hematopoiesis; Infections; Leukocyte Count; Leukopenia; Mechlorethamine; Mercaptopurine; Models, Biological; Pyrimidines; Thiotepa; Triethylenemelamine; Vinblastine; Vincristine

Topics: Absorption; Animals; Chromium Isotopes; Cortisone; Erythrocytes; Eye Diseases; Hemoglobins; Hemorrhage; Hypersensitivity; Infections; Inflammation; Injections; Iron; Mercaptopurine; Prednisolone; Rabbits; Uveitis; Vitreous Body

Topics: Adrenal Cortex Hormones; Animals; Bone Marrow Diseases; Dactinomycin; Dogs; Drug Synergism; Gastrointestinal Diseases; Graft vs Host Disease; Graft vs Host Reaction; Humans; Immunosuppressive Agents; Infections; Mercaptopurine; Rabbits; Transplantation, Homologous

The therapy of acute leukemia has improved rapidly in the last two decades. Using available therapeutic agents, complete clinical and hematological remission can be achieved regularly in children with acute lymphocytic leukemia. The choice of chemotherapeutic agent, management of complications of hemorrhage and infection, and recognition of prognostic factors are important for the induction of a hematological remission. While patients in complete hematological remission are free of evidence of disease they still have residual leukemic cells, but in our present state of knowledge and with available techniques, we are unable to detect these. For this reason it is important to treat patients while in remission. The importance of dosage schedule for remission maintenance chemotherapy is stressed.In patients studied to date, regardless of the treatment used, the disease has recurred eventually. Available therapeutic agents are highly effective and highly selective, but they still fall short of providing ideal control of the disease. The continuing search for new chemotherapeutic agents is aided by the knowledge gained and techniques developed with current agents.

Topics: Adult; Anti-Bacterial Agents; Child; Cyclophosphamide; Hemorrhage; Humans; Infections; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Uric Acid; Vincristine

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Antibiotics, Antineoplastic; Bone Marrow Examination; Child; Child, Preschool; Cyclophosphamide; Drug Synergism; Female; Humans; Infections; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Middle Aged; Patient Isolators; Prednisone; Vincristine

Topics: Antineoplastic Agents; Cortisone; Cyclophosphamide; Folic Acid Antagonists; Hemostasis; Infections; Leukemia; Leukemia, Experimental; Lymphoma; Mercaptopurine; Mice; Penicillins; Rats; Research