Study Evaluates Link Between ALC Recovery, Viral Reactivation After Haploidentical HSCT

A recent study suggests that cytomegalovirus (CMV) reactivation does not correlate with absolute lymphocyte count (ALC) recovery after haploidentical hematopoietic stem cell transplantation (HSCT).

Mollee Chu, MD, of the University of Southern California, and colleagues conducted the study and presented their findings during the 2023 American Society of Clinical Oncology Annual Meeting.

They conducted the study because the “impact of early absolute lymphocyte repopulation after allogeneic HSCT has historically been shown to predict the risk of post-transplant infection, and subsequently, non-relapse mortality.” Furthermore, previous studies have shown that ALC recovery after allogeneic HSCT is “associated with risk of viral reactivation and survival,” according to Dr. Chu and colleagues.

Due to this, they investigated the role of ALC recovery in patients who received myeloablative conditioning for haploidentical HSCT by conducting a retrospective analysis of adults who underwent the procedure between 2014 and 2020. The study’s primary endpoint was the correlation between ALC recovery at day 21 and the risk of viral reactivation, including CMV, Epstein-Barr virus (EBV), and BK virus. Based on prior reports, they defined the ALC recovery cutoff as 175/on day 60.

Dr. Chu and colleagues identified 58 patients who received myeloablative conditioning for haploidentical HSCT. Of those patients, 17 had ALC recovery at day 21. The mean patient age was 49 years and about half (53.4%) were male. Most patients (70%) were Hispanic, and 20% were White. About half (51%) of patients had acute myeloid leukemia.

Most patients (76%) received a dose of more than 5×10⁶/kg CD34-positive cells, and 78% received a dose of less than 5×10⁶/kg CD3-positive cells. Nearly two-thirds (65.5%) of patients had detectable CMV in serum, 15.7% had detectable EBV, and 32.4% had detectable BK virus.

Less than half (44.8%) of patients had “clinically significant” CMV reactivation that required antiviral therapy. However, a lack of ALC recovery at day 21 was not correlated with reactivation of CMV, EBV, or BK virus. Furthermore, the risk of CMV reactivation was not related to ALC recovery at day 60 (P=.469). A univariate analysis showed ALC recovery at day 21 and CMV reactivation were not correlated with overall survival. A multivariate analysis showed a higher CD3-positive cell dose was associated with a reduced risk of CMV reactivation (hazard ratio, 0.35; P=.02).

“Our study shows that lack of ALC recovery on day +21 does not affect CMV, EBV and BK virus reactivation and risk of CMV reactivation does not correlate with day 60 ALC recovery,” Dr. Chu and colleagues concluded. “Also, ALC recovery and CMV reactivation does not impact overall survival. The use of letermovir, effective CMV therapies, and close viral surveillance in contemporary practice is likely responsible for mitigating poor outcomes with CMV reactivation. Graft composition needs to be studied prospectively, as higher CD3-positive cell dose may present an opportunity to reduce CMV reactivation in [haploidentical] HSCT.”

Reference

Chu MI, Ashouri K, Chennapan K, et al. Absolute lymphocyte counts (ALC) recovery and risk of viral reactivation in the setting of haploidentical hematopoietic stem cell transplant. Abstract e19065. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.