The influence of human leukocyte antigens in graft versus host disease and survival after hematopoietic stem cell transplantation in pediatric patients with leukemia

Abstract

Objective: Hematopoietic stem cell transplantation (HSCT) is an important therapy for hematological diseases. One of the most significant complications of HSCT is graft versus host disease (GVHD), and major histocompatibility complex (MHC) is well known to affect GVHD and graft rejection. This study aimed to examine the effect of human leukocyte antigens (HLA) on the incidence of GVHD development in patients with leukemia.

Methods: The association between HLA and GVHD formation was evaluated in 57 patients with HSCT with HLA-identical sibling donors, of whom 37 were boys and 20 were girls with a mean age of 10.11 years. All patients were diagnosed with leukemia; acute myeloid leukemia (n=33), acute lymphoblastic leukemia (n=15), and chronic myeloid leukemia (n=9). Transplantation pairs were worked for HLA-A,-B,-C, and-DRB1 alleles. Class I HLA antigens were investigated using Terasaki microlymphocytotoxicity, whereas class II HLA alleles with polymerase chain reaction -sequence-specific amplification method.

Results: The frequency of developing GVHD in patients with HSCT was found to be 17.5% (n=10). HLA-DRB1*04 allelic frequency [p=0.024, odds ratio (OR): 4.87] was found to be higher in patients who developed GVHD. However, the HLA-DRB1*11 allelic frequency (p=0.031, OR: 0.12) was lower in patients who developed GVHD compared to patients who did not develop GVHD. Furthermore, HLA-B38 (p=0.002) and HLA-B41 (p=0.002) antigens were found only in patients who developed GVHD. The frequencies of the HLA-A26 allele (p=0.12) and the HLADRB1*11 allele (p=0.037, OR: 4.0) were higher in patients with relapse after HSCT; however, the frequencies of the HLA-A2 allele (p=0.033, OR: 0.19) was lower in patients who relapsed after HSCT.

Conclusion: This study assessed the relationship of HLA class with GVHD, relapse, and survival in children after HSCT in pediatric patients with leukemia.

Amaç: Hematopoetik kök hücre nakli (HKHN), hematolojik hastalıklar için önemli bir tedavidir. HKHN’nin en önemli komplikasyonlarından biri, graft-versus-host hastalığıdır (GVHH) ve büyük doku uyumluluk kompleksinin (major histocompatibility complex-MHC) GVHH ve greft reddini etkilediği iyi bilinmektedir. İnsan lökosit antijenleri (human leukocyte antigen - HLA) tipinin lösemili hastalarda GVHH insidansı üzerindeki etkisini incelemeyi amaçladık. Gereç ve Yöntem: HLA uyumlu kardeş donörleri ile HKHN olan 57 hastada HLA ve akut, kronik GVHH oluşumu arasındaki ilişki değerlendirildi. Çalışmaya yaş ortalaması 10,11 olan 37 erkek ve 20 kız dahil edildi. Tüm hastaların tanıları; Akut myeloid lösemi (n=33), akut lenfoblastik lösemi (n=15), kronik myeloid lösemi (n=9) idi. Tüm nakil kardeş çiftleri HLA-A, -B, -C, -DRB1 allelleri için tiplendirildi. Sınıf I HLA antijenleri Terasaki mikrolenfositotoksisite kullanılarak saptandı ve sınıf II HLA allelleri polimeraz zincir reaksiyonu-diziye özgü primerler (polymerase chain reaction with specific primer sequence) yöntemi ile analiz edildi. Bulgular: HKHN uygulanan hastalar arasında GVHH insidansı %17,5 (n=10) olarak bulundu. HLA-DRB1*04 allelik frekansı [p=0,024, risk oranı (OR): 4,87] GVHH gelişen hastalarda daha yüksekti. Bununla birlikte, HLA-DRB1*11 allelik frekansı (p=0,031, OR: 0,12), GVHH gelişen hastalarda, GVHH geliştirmeyen hastalara göre daha düşüktü. Ayrıca, HLA-B38 (p=0,002) ve HLA-B41 (p=0,002) antijenleri sadece GVHH gelişen hastalarda bulundu. HLA-A26 alelinin (p=0,12) ve HLA-DRB1*11 alelinin (p=0,037, OR: 4,0) frekansları daha yüksekken, HLA-A2 allelinin frekansları (p=0,033, OR: 0,19) HKHN sonrası nükseden hastalarda daha düşük olarak saptandı. Sonuç: Bu çalışma, lösemili pediatrik hastalarda HKHN sonrası çocuklarda HLA sınıfının GVHH, relaps ve sağkalım ile ilişkisini değerlendiren çalışmadır