mercaptopurine and Alopecia

Topics: Abnormalities, Drug-Induced; Alkylating Agents; Allopurinol; Alopecia; Antimetabolites; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Cyclophosphamide; Drug Synergism; Female; Fetus; Humans; Kidney Calculi; Kidney Diseases; Kidney Tubules; Mechlorethamine; Mercaptopurine; Neoplasms; Pregnancy; Pregnancy Complications; Uric Acid; Vincristine

Topics: Alopecia; Aminopterin; Antimetabolites; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Bone Marrow Diseases; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Cystitis; Female; Herpes Zoster; Humans; Jaundice; Mechlorethamine; Mercaptopurine; Methotrexate

Topics: Alopecia; Aminopterin; Antimetabolites; Antineoplastic Agents; Arthritis, Rheumatoid; Azathioprine; Bone Marrow Diseases; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Cystitis; Female; Herpes Zoster; Humans; Jaundice; Mechlorethamine; Mercaptopurine; Methotrexate

Topics: Alopecia; Antibody Formation; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Chromosome Aberrations; Daunorubicin; Drug Hypersensitivity; Heart; Humans; Immunosuppressive Agents; Inflammation; Intestinal Mucosa; Leukemia; Leukocytes; Leukopenia; Lymphocyte Activation; Mercaptopurine

Topics: Adolescent; Alopecia; Child; Child, Preschool; Cyclophosphamide; Cystitis; Drug Synergism; Female; Humans; Leukemia; Male; Mercaptopurine; Prednisone

Though not exempt from adverse events, azathioprine (AZA) is an inexpensive and effective drug in the induction and maintenance treatment of patients with inflammatory bowel disease. We present the case of a 20-year-old female patient with left-side ulcerative colitis in whom AZA was started at a dose of 1.5 mg/kg/day due to dependence on corticoids (thiopurine methyltransferase activity: 14.9 U/mL). Two weeks after starting treatment she began to report excessive hair loss, resulting in an almost complete loss of scalp hair.

Topics: Adult; Alopecia; Azathioprine; Biomarkers; Colitis, Ulcerative; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Methyltransferases; Young Adult

Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs.. Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation.. We confirmed the association of NUDT15 p.Arg139Cys with leukopenia and alopecia (p = 2.20E-63, 1.32E-69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E-04, OR = 1.89). Time to leukopenia was significantly shorter, and when leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of leukopenia frequency with estimated enzyme activities based on the diplotypes (r. Genotyping of NUDT15 codon 139 was sufficient to predict acute severe leukopenia and alopecia in Japanese patients with IBD.

Topics: Alopecia; Antibodies, Monoclonal; Azathioprine; Biomarkers, Pharmacological; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomic Structural Variation; Haplotypes; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Japan; Leukopenia; Logistic Models; Mercaptopurine; Mesalamine; Pharmacogenetics; Pyrophosphatases; Retrospective Studies; Risk; ROC Curve; Sulfasalazine

The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg(-1) per day vs 1.03±0.425 mg kg(-1) per day, P=6.21 × 10(-4)). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with t

Topics: Adult; Alopecia; Anti-Inflammatory Agents; Asian People; Azathioprine; Chi-Square Distribution; Colitis, Ulcerative; Crohn Disease; Dose-Response Relationship, Drug; Female; Gastrointestinal Agents; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Japan; Kaplan-Meier Estimate; Leukopenia; Logistic Models; Male; Mercaptopurine; Middle Aged; Multivariate Analysis; Odds Ratio; Phenotype; Pyrophosphatases; Risk Factors; Severity of Illness Index; Treatment Outcome; Young Adult

NUDT15 R139C (rs116855232) is a recently identified genetic factor responsible for thiopurine-induced leukocytopenia and hair loss. In this study, we investigated the association of NUDT15 R139C with 6-thioguanine nucleotide (6-TGN) levels and thiopurine-induced leukocytopenia in Japanese patients with inflammatory bowel disease (IBD).. Two hundred and sixty-four subjects (103 healthy volunteers and 161 IBD patients treated with thiopurines) were enrolled. Genotyping for NUDT15 R139C was performed using Custom TaqMan® SNP genotyping assays.. The NUDT15 C/C, C/T, and T/T genotypes were 80.7, 18.2, and 1.1 %, respectively. The allelic frequency was 10.2 %. Among 161 IBD patients, there was no significant difference in 6-TGN levels among the NUDT15 genotypes. Forty-five patients (27.9 %) developed leukocytopenia (WBC <3000/μl), and the C/T and T/T genotypes were significantly associated with the development of leukocytopenia (P = 1.7 × 10(-5)). In these patients, 6-TGN levels were not significantly different between NUDT15 genotypes. NUDT15 R139C was significantly associated with early (<8 weeks) (P = 1.03 × 10(-4)) and late (>8 weeks) leukocytopenia (P = 4.3 × 10(-4)). The decrease in WBC count at 2 and 4 weeks was significantly higher in patients with the C/T or T/T genotypes as compared to the patients with the C/C genotype. All patients with the T/T genotype (n = 2) developed early severe hair loss and severe leukocytopenia (<1000/μl). The logistic regression analysis revealed that NUDT15 R139C was the sole genetic factor responsible for the thiopurine-induced leukocytopenia (P = 0.001).. These results suggest that NUDT15 R139C-related thiopurine-induced leukocytopenia is mediated by a 6-TGN-independent mechanism.

Topics: Adult; Alopecia; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Guanine Nucleotides; Humans; Inflammatory Bowel Diseases; Leukocyte Count; Leukopenia; Male; Mercaptopurine; Middle Aged; Pyrophosphatases; Thionucleotides

Topics: Adolescent; Alopecia; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow; Crohn Disease; Drug Hypersensitivity; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Mercaptopurine; Mesalamine; Methyltransferases; Pancytopenia; Phenotype; Purine-Pyrimidine Metabolism, Inborn Errors

A 15-year-old, woman, Crohn's disease patient, who carried the TPMT *3C heterozygous mutant, complained of alopecia 3 days after starting 6-mercaptopurine (6-MP) and then developed severe myelosuppression 6 weeks after starting 6-MP. The alopecia involved scalp hair only (body hair preserved) and was dominant in the temporal region. Following these side effects, transient remission of Crohn's disease occurred. Myelosuppression due to 6-MP is a rare but life-threatening side effect that is difficult to predict despite continuous monitoring of complete blood cell counts. In the present case, 6-MP-induced alopecia preceded myelosuppression and progressed rapidly as the myelosuppression worsened.

Topics: Adolescent; Alopecia; Bone Marrow; Crohn Disease; Female; Humans; Mercaptopurine

Active hexose correlated compound (AHCC) (a mixture of polysaccharides, amino acids, lipids and minerals derived from cultured mycelia of a Basidiomycete mushroom, Lentinula edodes) was used to assess amelioration of alopecia (hair loss) caused by cytosine arabinoside (Ara-C) and modulation of liver injury caused by single doses 6-mercaptopurine (6-MP) plus methotrexate (MTX).. Follicular integrity and hair growth was assessed in male and female SD neonatal rats (8 days old) treated with a single dose of Ara-C (30 mg/kg/day, i.p.) and AHCC (500 mg/kg/day, p.o.) for 7 consecutive days. The side effects of a single oral dose of 6-MP (2.5mg/kg body weight) plus MTX (30 mg/kg body weight) and their amelioration by treatment with AHCC (1000 mg/kg body weight) for 28 days were assessed in male ddY mice (8 weeks old).. Of the Ara-C treated rats 71.4% showed severe alopecia and 28.6% showed moderate alopecia. However, the AHCC (p.o.)-treated Ara-C group was significantly protected from alopecia. Ara-C treated rats had profound loss of hair follicles but the Ara-C plus AHCC-treated group had mild losses of follicles. AHCC supplementation to the 6-MP- and MTX-treated mice significantly increased body weight, erythrocytes, leukocytes and serum albumin, improved liver hypertrophy and degeneration, normalized the activities of serum glutamic oxaloacetic transaminase (sGOT) and serum glutamic pyruvic transaminase (sGPT), and enhanced liver drug-metabolizing enzymes.. Co-administration of AHCC significantly reduced the side effects associated with Ara-C, 6-MP and MTX. However, the molecular mechanism for AHCC activity and its clinical integrity for use needs defining.

Topics: Alopecia; Animals; Animals, Newborn; Antimetabolites, Antineoplastic; Body Weight; Cytarabine; Female; Hair Follicle; Male; Mercaptopurine; Methotrexate; Mice; Polysaccharides; Rats; Rats, Sprague-Dawley; Shiitake Mushrooms

In accordance with the recommendations of Pinkel, 147 children with acute lymphoblastic leukemia were treated by a combined cytostatic and radiation therapy during a joint study between May 1971 and Jan. 1, 1974. After a primary cytostatical treatment which brought about a remission of 94% of the patients within four to six weeks, the cranial irradiation was performed, depending on age, with a focal dose of 1500 up to 2400 rd in the course of three or four weeks. Simultaneously, the patients were given methotrexate intrathecally which was followed, later on, by a long-term therapy with cytostatics. By means of this combined treatment, a three-year survival was obtained in 50% (8 of 16) and a complete remission in 44% (7 of 16). The prognosis is the same for boys as for girls. A less favorable prognosis concerns the patients with an initial leukocytosisf more than 50 000 leukocytes/mm3 of blood, an age of more than ten years, and leukemic cells already demonstrable in the cerebrospinal fluid.

Topics: Acute Disease; Adolescent; Age Factors; Alopecia; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Premedication; Prognosis; Radiotherapy; Radiotherapy Dosage; Remission, Spontaneous; Skull; Vincristine

Topics: Adolescent; Adult; Aged; Alopecia; Ampicillin; Anemia, Aplastic; Antibiotics, Antineoplastic; Blood Platelets; Blood Transfusion; Cardiomyopathies; Cephaloridine; Electrocardiography; Female; Heart; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Paresthesia; Remission, Spontaneous; Sulfamethoxazole; Thrombocytopenia; Trimethoprim

Topics: Alopecia; Azathioprine; Child, Preschool; Cyclophosphamide; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Leukopenia; Mercaptopurine; Nephrosis, Lipoid; Nephrotic Syndrome