J Korean Rheum Assoc.  2007 Jun;14(2):144-148. 10.4078/jkra.2007.14.2.144.

Severe Leukopenia after Intravenous Cyclophosphamide Pulse Therapyin a Patient Having Cytochrome P450 2A6*1B

Affiliations
  • 1Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, Seoul, Korea. scbae@hanyang.ac.kr
  • 2Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Korea.
  • 3Department of Internal Medicine, Konyang University, Daejeon, Korea.

Abstract

Cyclophosphamide, a prodrug requiring metabolic activation by cytochrome P450 (CYP) enzymes, is used widely for proliferative lupus nephritis and various CYP isoenzymes have been demonstrated to be involved in the bioactivation of cyclophosphamide in humans, including CYP2A6, 2B6, 2C19, 2C9, 3A4, and 3A5. The response or adverse event after intravenous cyclophosphamide pulse therapy in lupus nephritis patient seems to be different for each individual and genetic polymorphism of CYP may explain the difference. Generally, wild types of CYP seem to be more active in the activation of cyclophosphamide than variant types of CYP. Here, we report a case of lupus nephritis with a genotype of CYP2A6*1B who suffered from severe leukopenia after intravenous cyclophosphamide pulse therapy.

Keyword

Cyclophosphamide; Leukopenia; Cytochrome P450

MeSH Terms

Biotransformation
Cyclophosphamide*
Cytochrome P-450 Enzyme System*
Cytochromes*
Genotype
Humans
Isoenzymes
Leukopenia*
Lupus Nephritis
Polymorphism, Genetic
Cyclophosphamide
Cytochrome P-450 Enzyme System
Cytochromes
Isoenzymes

Figure

  • Fig. 1. Time course of the values for leukocyte, neutrophil and 24 hour proteinuria. IC: intravenous cyclophosphamide pulse therapy, G-CSF: granulocyte colony stimulating factor. Leukocyte and neutrophil count are expressed in mm3 and proteinuria is expressed in mg/day.

  • Fig. 2. Result of genotype. PCR-RFLP method was used for the analyses of CYP2A6, CYP2B6, CYP3A4, and CYP3A5. Pyrosequencing method for CYP2CP analysis and both method were used for CYP2C19 analysis. The patient had polymorphism in CYP2A6 and CYP3A5; CYP2A6∗1B/∗1B and CYP3A5∗3/∗3.


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