HLA-DR9 and DR14 Are Associated with the Allopurinol-Induced Hypersensitivity in Hematologic Malignancy

HLA-DR9 and DR14 Are Associated with the Allopurinol-Induced Hypersensitivity in Hematologic Malignancy

JAE-WOO JUNG,^1,2,3 JU-YOUNG KIM,^2,4 SUNG-SOO YOON,⁴ SANG-HEON CHO,^1,2,4 SEON-YANG PARK⁴ and HYE-RYUN KANG^1,2,4

¹Drug Safety Monitoring Center, Seoul National University Hospital, Seoul, Korea
²Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
³Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
⁴Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Allopurinol, a widely used urate-lowering agent, is a leading cause of severe cutaneous adverse reactions (SCARs), especially in patients with HLA-B*58:01. Despite its routine use for the prevention of tumor lysis-related hyperuricemia prior to chemotherapy, the risk of allopurinol-induced hypersensitivity has not been investigated in patients with hematologic malignancies. This retrospective cohort study was conducted to investigate the incidence and risk factors of allopurinol-induced hypersensitivity in patients at least 18 years of age with hematologic malignancies. We reviewed 463 patients who had ever taken allopurinol for the prevention of hyperuricemia prior to chemotherapy and had undergone serologic HLA typing as a pre-transplant evaluation from January 2000 to May 2010. Thirteen (2.8%) patients experienced maculopapular eruptions (MPE) and none experienced SCARs. Among subtypes of underlying hematologic malignancies, percentage of chronic myeloid leukemia was significantly higher in the allopurinol hypersensitivity group compared with the tolerant group (23.1% (3/13) vs. 5.9% (26/440), P = 0.044). According to HLA subtypes, the incidence of allopurinol-induced MPE was 4.0% in HLA-B58 (+) patients (2/50) and 2.7% in HLA-B58 (−) patients (11/403) but this difference was statistically insignificant. In contrast to HLA-B58, the frequencies of DR9 and DR14 were significantly higher in the allopurinol-induced MPE group compared with the allopurinol tolerant group (38.5% (5/13) vs. 13.6% (53/443), P = 0.019, and 38.5% (5/13) vs. 15.6% (41/440), P = 0.038, respectively). In conclusion, HLA-DR9 and DR14, but not HLA-B58, are associated with hypersensitivity reaction by allopurinol when administered in patients with hematologic malignancy prior to chemotherapy.

keywords —— Keywords: allopurinol; hematologic malignancy; human leukocyte antigen; Koreans; maculopapular eruptions

===============================

Tohoku J. Exp. Med., 2014, 233, 95-102

Correspondence: Hye-Ryun Kang, M.D., Ph.D., Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.

e-mail: helenmed@snu.ac.kr