HLA and Kir Mismatch Transplant Affect Cytopenia Beyond Day 28 after Thalassemia Transplant: A Primary Manifestation of Chronic Graft Versus Host Disease

Background Cytopenia beyond day 28 post-transplant (CB-28PT) following hematopoietic stem cell transplantation (HSCT) with β-thalassemia major (TM) rarely was reported. The exact mechanism for the development of CB-28PT is not well known.

Aim To find out causes of CB-28PT cytopenia.

Method We retrospectively analyzed data (HLA mismatch status, HLA antibody status of patients, KIR gene mismatch status, KIR-ligand matching status, donor/patient CMV status, donor/patient age and sex) of 93 TM patients underwent HLA 8/8 fully matched or 7/8 matched unrelated donor HSCT. All the patients used sole NF-08-TM protocol with median follow-up time of 19 (r: 2-44) months.

Results Results show a significant association between DRB1 mismatch and CB-28PT (P = 0.012). In addition, presence of Class I HLA antibody in the patient’s sera seems increase the chance of CB-28PT. Finally, the matching between inhibitory KIR2DL1 and their corresponding ligand HLA-C2 has a protective effect for CB-28PT.

Conclusion We propose that CB-28PT may be a primary manifestation of cGVHD in pediatric TM patients undergoing HSCT positive influenced by HLA DRB1 mismatch, HLA class I antibody and negatively affected by KIR-ligand match.