Azathioprine-related myelosuppression in a patient homozygous for TPMT☆3A

被引:19
作者
Budhiraja, Pooja [1 ]
Popovtzer, Mordecai [1 ]
机构
[1] So Arizona Vet Affairs Hlth Care Syst, Tucson, AZ 85723 USA
关键词
INFLAMMATORY-BOWEL-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; THIOPURINE METHYLTRANSFERASE ACTIVITY; TRANSPLANT RECIPIENTS; TPMT; GENOTYPE; MERCAPTOPURINE; PHENOTYPE; PHARMACOGENETICS; 6-MERCAPTOPURINE;
D O I
10.1038/nrneph.2011.74
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. A 50-year-old man who had received a simultaneous pancreas and kidney transplant 9 years earlier developed pancytopenia 3 weeks after starting azathioprine therapy to treat worsening proteinuria suspected to be caused by sirolimus. Investigations. Laboratory tests, including complete blood counts, measurement of serum levels of vitamin B-12 and folate, liver function tests, virological assays, and thiopurine S-methyltransferase (TPMT) genotyping. Diagnosis. Severe myelosuppression as a consequence of azathioprine therapy in a patient homozygous for the TPMT(star)3A allele. Management. Discontinuation of azathioprine, treatment with an erythropoiesis-stimulating agent, red blood cell transfusions, filgrastim (a granulocyte colony-stimulating factor analogue) and folic acid.
引用
收藏
页码:478 / 484
页数:7
相关论文
共 30 条
[11]   Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine [J].
Evans, WE ;
Hon, YY ;
Bomgaars, L ;
Coutre, S ;
Holdsworth, M ;
Janco, R ;
Kalwinsky, D ;
Keller, F ;
Khatib, Z ;
Margolin, J ;
Murray, J ;
Quinn, J ;
Ravindranath, Y ;
Ritchey, K ;
Roberts, W ;
Rogers, ZR ;
Schiff, D ;
Steuber, C ;
Tucci, F ;
Kornegay, N ;
Krynetski, EY ;
Relling, MV .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (08) :2293-2301
[12]   Heterozygosity at the TPMT gene locus, augmented by mutated MTHFR gene, predisposes to 6-MP related toxicities in childhood ALL patients [J].
Karas-Kuzelicki, N. ;
Jazbec, J. ;
Milek, M. ;
Mlinaric-Rascan, I. .
LEUKEMIA, 2009, 23 (05) :971-974
[13]   TPMT but not ITPA gene polymorphism influences the risk of azathioprine intolerance in renal transplant recipients [J].
Kurzawski, Mateusz ;
Dziewanowski, Krzysztof ;
Lener, Agnieszka ;
Drozdzik, Marek .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2009, 65 (05) :533-540
[14]   Thiopurine methyltransferase phenotype and genotype in relation to azathioprine therapy in autoimmune hepatitis [J].
Langley, PG ;
Underhill, J ;
Tredger, JM ;
Norris, S ;
McFarlane, IG .
JOURNAL OF HEPATOLOGY, 2002, 37 (04) :441-447
[15]   CONGENITAL THIOPURINE METHYLTRANSFERASE DEFICIENCY AND 6-MERCAPTOPURINE TOXICITY DURING TREATMENT FOR ACUTE LYMPHOBLASTIC-LEUKEMIA [J].
LENNARD, L ;
GIBSON, BES ;
NICOLE, T ;
LILLEYMAN, JS .
ARCHIVES OF DISEASE IN CHILDHOOD, 1993, 69 (05) :577-579
[16]   THIOPURINE PHARMACOGENETICS IN LEUKEMIA - CORRELATION OF ERYTHROCYTE THIOPURINE METHYLTRANSFERASE ACTIVITY AND 6-THIOGUANINE NUCLEOTIDE CONCENTRATIONS [J].
LENNARD, L ;
VANLOON, JA ;
LILLEYMAN, JS ;
WEINSHILBOUM, RM .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1987, 41 (01) :18-25
[17]   Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: A meta-analysis [J].
Osterman, MT ;
Kundu, R ;
Lichtenstein, GR ;
Lewis, JD .
GASTROENTEROLOGY, 2006, 130 (04) :1047-1053
[18]   Human thiopurine methyltransferase pharmacogenetics: Gene sequence polymorphisms [J].
Otterness, D ;
Szumlanski, C ;
Lennard, L ;
Klemetsdal, B ;
Aarbakke, J ;
ParkHah, JO ;
Iven, H ;
Schmiegelow, K ;
Branum, E ;
OBrien, J ;
Weinshilboum, R .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1997, 62 (01) :60-73
[19]   Mechanistic mathematical modelling of mercaptopurine effects on cell cycle of human acute lymphoblastic leukaemia cells [J].
Panetta, JC ;
Evans, WW ;
Cheok, MH .
BRITISH JOURNAL OF CANCER, 2006, 94 (01) :93-100
[20]   TPMT genotype screening for patients about to begin azathioprine treatment - A look at costs and potential benefits [J].
Provenzale, D ;
Onken, JE .
INFLAMMATORY BOWEL DISEASES, 2005, 11 (12) :1119-1120