nLower incidence of Cytomegalovirus reactivation following post-transplant cyclophosphamide HLA mismatched unrelated donor transplantation

ABSTRACT Background The use of haploidentical or HLA mismatched unrelated donors (MMUD) allows allogeneic hematopoietic cell transplantation (HCT) in individuals without suitable matched donors. Post-transplant cyclophosphamide (PTCy) is used routinely for prevention of graft-versus-host disease (GVHD) in recipients of haploidentical transplants and its use has been recently explored in MMUD transplantation. Objectives Compare the incidence of cytomegalovirus (CMV) reactivation and rate of lymphocyte recovery between PTCy MMUD and alternative transplant modalities. Study design Single-center retrospective study of 22 consecutive PTCy MMUD recipients transplanted between April 2017 and January 2019. Patients undergoing anti-thymocyte globulin (ATG) MMUD (n=37) and PTCy haploidentical transplantation (n=19) between January 2015 and July 2018 served as historical controls. We assessed the incidence of CMV (any viremia) and clinically significant CMV reactivation (cs-CMVi; defined as CMV disease or CMV viremia leading to preemptive treatment) in these 3 groups. Immune reconstitution was assessed by absolute lymphocyte count (ALC) at days 30, 90, 180 and 360 post-transplant. Statistical analyses included Kaplan-Meier plots with a log-rank test, Kruskal–Wallis test, and Fisher's exact test where appropriate, and logistic regression analyses. Results For PTCy MMUD, PTCy haploidentical and ATG MMUD groups, the 100-day and 200-day incidence of CMV (any viremia) were 41, 63 and 77% (P=0.02), and 64, 68, and 86% (P=0.049), respectively. cs-CMVi was also lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (14 vs. 53 and 54% at day 100, P=0.01; and 25 vs. 53 and 58% at day 200, P=0.03). There was a trend towards lower 200-day incidence of cs-CMVi in PTCy MMUD compared to ATG MMUD, even after excluding letermovir treated patients from the analysis (25 vs. 58%; P=0.06). The association between PTCy MMUD and lower risk of cs-CMVi remained significant even after adjusting for letermovir prophylaxis (OR, 0.23, 95% CI 0.07 - 0.81; P=0.02). Day 30 ALC was lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (0.14, 0.33, 0.44 × 109/L respectively, P=0.005) but similar across groups at other time points. Conclusions PTCy MMUD transplantation was associated with lower incidence of CMV events, independent of the use of CMV prophylaxis. Larger studies are needed.