Cytomegalovirus Infection after CD34+-Selected Hematopoietic Cell Transplantation

Abstract

Background The effectiveness of preemptive treatment (PET) for CMV in recipients of ex vivo T-cell depleted (TCD) hematopoietic cell transplantation (HCT) by CD34+ selection is not well defined. Methods We analyzed 213 adults who received TCD-HCT at our institution from June 2010 through May 2014. Patients were monitored by a CMV quantitative PCR assay if recipient (R) or donor (D) were CMV seropositive. Results CMV viremia occurred early (median 27 days post HCT) in 91 of 213 (42.7%) patients for a180-day cumulative incidence of 84.5%, 61.8%, and 0 for R+/D+, R+/D−, R−/D+ patients, respectively. CMV disease occurred in 5% of patients. In Cox regression analysis, R+/D+ status was associated with increased risk for CMV viremia compared to R+/D− (hazard ratio, HR: 1.79, 95% confidence interval, CI: 1.16–2.76, P=0.01) while matched unrelated donor allograft was associated with decreased risk (HR: 0.62, 95% CI: 0.39–0.97, P=0.04). Of 91 patients with CMV viremia, 52 (57%) had persistent viremia (>28 days duration). Time lag from detection of CMV viremia to PET was associated with incremental risk for persistent viremia (HR: 1.09, 95%CI: 1.01–1.18; P=0.03). Overall, 166 of 213 (77.9%) patients were alive one-year post-HCT with no difference between patients with and without CMV viremia or among the different CMV serostatus pairs (P=NS). Conclusions CMV viremia occurred in 70% of R+ TCD-HCT. Delay in PET initiation was associated with persistent viremia. With PET, CMV R/D serostatus did not adversely impact survival in TCD-HCT on one-year survival in the present cohort.

Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell–Depleted, CD34+ Selected Hematopoietic Cell Transplantation

“…Ex vivo T-cell depletion is associated with increased incidence of viral infections 3 . We have previously reported rates and outcomes of CMV and ADV viremia after ex vivo TCD HCT using the currently FDA-approved method for CD34 + selection 8, 9 . In the present study we report the aggregate burden of infection and health care utilization associated with dsDNA viruses in a contemporary cohort of CD34 + HCT recipients routinely monitored by quantitative PCR assays.…”

“…All patients received acyclovir prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) per institutional standards of care 8 . CMV was routinely monitored at least weekly from day +14 through day +100, at least every 14 days from day+100 until day +180 and thereafter as clinically indicated.…”

“…T-cells are essential for control of double stranded DNA (dsDNA) viruses including cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6) and Epstein-Barr virus (EBV) 6, 7 . Among CMV seropositive recipients (R+) of TCD allograft, the reported rate of CMV viremia is approximately 70% and the rate of disease is up to 10% 8 . The reported incidence of ADV viremia in TCD allograft is approximately 8% with >30% of patients with ADV viremia developing ADV end-organ disease (EOD) 9 .…”

Herpesvirus infection following allogenic hematopoietic stem cell transplantation with TCRaβ and CD19 depletion: risk factors and outcome

“…Однако стоит отметить, что исполь-зование альтернативных методов (in vivo, ex vivo) Т-клеточной деплеции при ТГСК от гаплоидентичного донора, включая CD34-селекцию, алемтузумаб и пост-трансплантационный циклофосфамид, в равной сте-пени обусловливает повышение вероятности ЦМВ-ви-ремии [31][32][33][34]. Единственным достоверным отличием от нашей группы пациентов является тот факт, что при использовании платформы CD34-селекции не отмечено переноса цитомегаловируса ЦМВ-негатив-ному реципиенту от ЦМВ-позитивного донора [34]. Это наблюдение косвенно свидетельствует о том, что моноциты трансплантата, удаляемые при CD34-се-лекции, сохраняются в TCRaβ и CD19 деплетирован-ном трансплантате и, вероятно, служат резервуаром для трансмиссии ЦМВ.…”

“…В моно-и мультива-риантных анализах получено значимое влияние на риск ЦМВ-виремии, предшествующей острой РТПХ > II стадии, серопозитивности реципиента до ТГСК и наличия у пациента злокачественного заболевания. КВ ЭБВ-инфекции -33% (95% ДИ [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. Фактором риска ЭБВ-виремии являлась острая РТПХ > II стадии.…”