HSCT PATIENTS with HHV6 Reactivation HAD LOW NUMBERS of CD4+ Effector Memory Lymphocytes IN BLOOD WHAT Associates with Rather POOR SURVIVAL.

Abstract 4555

It is known that the pace of immunological recovery influences the outcome of HSCT and herpes viruses reactivation contributes significantly to the post transplant mortality.

The aim of this study was to investigate reconstitution of subpopulations of CD4+ lymphocytes in the context of β-herpes viruses reactivation shortly post HSCT. There were two observation points: (1) at the beginning of lymphocyte recovery (number of lymphocytes > 200 cells/ul) which was seen from 9 to 31 day post HSCT median 14 and (2) 3 weeks later (median day 35 range(31-53)). CD4+ T cell subsets were defined as follow: Naive cells (N) CD4+CCR7+CD45RA+, Central memory (CM) CD4+CCR7+CD45-, Effector memory(EM) CD4+CCR7-CD45+, Terminally differentiated memory cells (TEMRA) CD4+CCR7-CD45RA+ . CMV, EBV and HHV-6 DNA copies were detected in blood with the use of QT-PCR in one week intervals. The study included 44 patients (age 1 to 64 median 45yr., 21 ric/mac, 21/23, sib/mud 21/23 mud, BM/PBPC 4/40.

It was found;

1. Fifteen, 13 and 4 patients were positive for EBV, HHV-6 and CMV DNA copies during the observation period.

(i) CD4+lymphocyte count was lower in patients having CMV copies as compared to those having EBV and/or HHV6 copies (both lymphocytotropic viruses) at the beginning of lymphocytes recovery (45/ul vs 120/ul p=0,047 Mann-Whitney U test), similarly behaved EM cells. 22/ul vs 84/ul EM cells (p= 0,088 Mann-Whitney U test) were seen in pts having CMV reactivation and in those with EBV and/or HHV-6 reactivation, respectively.

(ii) The situation changed three weeks later, it appeared that patients having HHV6 reactivation any time during the observation period had lower CD4+ lymphocyte numbers as compared to patients lacking β-herpes viruses reactivations (CD4+ cells median 93/ul vs190/ul; p=0,096 Mann-Whitney U test) and to those with CMV and EBV reactivation. Again EM cells contributed greatly to these differences. EM CD4+ lymphocytes were 41/ul, 105/ul, 80/ul and 160/ul in patients having HHV-6, CMV or EBV and lacking beta-herpes viruses reactivation, respectively. EM CD4+ lymphocyte numbers for HHV6+ patients as compared to patients lacking β-herpes viruses reactivations was 41/ul vs155/ul.(p=0,012 Mann-Whitney U test).

Conclusions: It appears that HHV6 is the main player in shaping lymphocyte reconstitution post transplant affecting predominantly EM cells what influences the outcome of transplantation. In this group of patients probability of one year survival was 50% vs 65%, in patients having and lacking HHV6, respectively.