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Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant recipients.

ABSTRACT: BACKGROUND:Cytomegalovirus (CMV) viremia after CD34+ -selected hematopoietic stem cell transplant (HCT) often requires prolonged antiviral therapy. We report rates and outcomes of resistant CMV in a contemporary cohort of CD34+ -selected HCT recipients managed preemptively. METHODS:We retrospectively reviewed 220 consecutive, CMV-seropositive recipients (R+), who received CD34+ -selected HCT at Memorial Sloan Kettering Cancer Center between June 2010 and December 2014. Patients were monitored by quantitative CMV PCR and were treated preemptively. CMV resistance was tested by a genotypic assay. RESULTS:One hundred and sixty-one (73%) patients developed CMV viremia and 47 (29% of viremic and 21% of total patients) had CMV resistance testing by one-year from HCT. CMV resistance was confirmed in 19 (12% of viremic and 9% of total) patients and was identified >3 months from HCT in 90% of patients. Twelve patients had mutations in UL97 only; the remaining 7 patients had mutations in UL54 only or UL54 and UL97. By 1 year from HCT, 11 of 19 (58%) patients with mutations had CMV end-organ disease. CMV-related mortality in patients with resistance was 42%. CONCLUSIONS:Nine percent of CMV R+, CD34+ -selected HCT recipients had resistant CMV by 1 year from HCT. Of 19 patients with resistant CMV, 58% had CMV end-organ disease and 42% died of CMV. Effective strategies for CMV prevention and restoration of CMV immunity are needed for CD34+ -selected HCT.

SUBMITTER: Kim SJ

PROVIDER: S-EPMC5988949 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Project description:Adenovirus (ADV) infections after hematopoietic cell transplantation (HCT) range in severity from self-limited to fatal. We have previously reported high mortality rates in CD34(+) selected T cell-depleted (TCD) HCT recipients using symptomatic testing and culture methods for ADV detection. We report rates and outcomes of ADV viremia in 215 adult recipients of TCD HCT using the CliniMACS CD34(+) selection system. This was a prospective observational study of adults transplanted from March 21, 2012 through November 30, 2014 at Memorial Sloan-Kettering Cancer Center. TCD was performed using CliniMACS CD34(+) cell selection. Patients were monitored for ADV by whole blood PCR assay from +14 to +100 days post-transplant. ADV viremia was defined as ?1 PCR above the lower limit of quantitation. ADV disease was defined per European Group for Blood and Marrow Transplantation guidelines. Treatment for ADV was at the clinician's discretion. Competing risk regression analyses were used to identify predictors for ADV viremia and overall survival. The median age was 55 years (range, 22 to 72); 215 patients underwent TCD. All patients received myeloablative conditioning. Eighteen patients (8% of cohort) had ADV viremia at a median onset of 57 days (interquartile range [IQR], 23 to 79) and with a median viral load at first detection of 2.6 log10 copies/mL (IQR, 2.5 to 4.0). The median maximal viral load was 4.5 log10 copies/mL (IQR, 3.5 to 5.9). No significant risk factor was identified for ADV viremia by univariate analysis. Six patients (3% of total cohort, 33% of viremic patients) developed ADV disease (3 colitis, 2 nephritis/cystitis, 1 pneumonitis). ADV viremia preceded onset of ADV disease a median of 11 days from the first positive quantitative PCR (range, +3 to +37) except in 1 patient with nephritis. Overall, 12 of 18 viremic patients (67%) received antiviral treatment (5 cidofovir only, 7 brincidofovir ± cidofovir). All patients with ADV disease were treated, and 6 patients were preemptively treated for ADV. Among the 18 viremic patients, 8 (44%) died during the study period, and, of those, 4 (22%) died of ADV. Early ADV viremia was infrequent (8%) among adult HCT recipients of CD34(+) selected allografts. Among viremic patients, rate of ADV disease was 33% and ADV attributable mortality was 22%. Further studies are needed to assess the impact of preemptive treatment with brincidofovir on improving outcomes of ADV infections in this patient population.

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Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant recipients.

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