Spontaneously‐resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes

Abstract

It has been reported that low‐plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously‐resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T‐cell replete allo‐HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 patients, of which 144 episodes cleared spontaneously. Clearance of CMV DNAemia was significantly delayed in initial and recurrent self‐resolving episodes featuring CMV DNA peak loads > 250 IU/mL compared with those displaying lower values. All‐cause mortality in patients with self‐resolving episodes of CMV DNAemia was comparable (P = 0.7) to that in patients with no CMV DNAemia and was not related to the CMV DNA peak load (≥250 IU/mL vs <250 IU/mL) (P = 0.6). In summary, in our setting, the magnitude of the CMV DNA peak load reached during self‐resolving episodes of CMV DNAemia correlated directly with duration of episodes, but had no apparent impact on all‐cause mortality taking patients with no documented CMV DNAemia as a reference.

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

“…experiencing self-resolving episodes of CMV DNAemia tended to be lower not only in patients with CMV DNAemia receiving PET but also in patients with no documented CMV DNAemia, in line with previous findings; 10,17 In these studies, 10,17 in which CMV DNA load prompting the initiation of PET was set at high level (>1500 IU/mL), it was hypothesized that clearance of CMV DNAemia in the absence of PET may merely reflect a timely and adequate immune reconstitution, which associates with increased survival. 1 In the current study, nevertheless, as underlined previously, low and high CMV DNA load cutoffs were established for PET initiation.…”

“…Finally, the hypothesis that the use of ganciclovir for PET may be detrimental for survival is pathogenically plausible given the toxicity inherent to use of ganciclovir, most notably neutropenia, 28 assay, whose intercenter variability appears to be reasonably low, 31 led us to conclude that withholding initiation of PET until a relatively high plasma CMV DNA load (between 500 and 1000 IU/mL) was documented did not increase OM and NRM through 1 year after allo-HSCT. In line with this observation, several studies [9][10][11][12]15,17,32,33 in which the cutoff for PET initiation was set at high CMV DNA load levels failed to find an association between CMV DNAemia and OM or NRM or found it only for patients who received PET. In some of these studies.…”

“…herein are concordant with previous observations made by 1 of the participating centers in this study 9,10,17 and other groups. 11,14,15 In these studies, [9][10][11]14,15,17 a relatively high CMV DNA load threshold (>1000 copies/mL/>1500 IU/mL) was set for PET inception, so that the possibility that use of PET simply behaved as a surrogate marker of deficient immune reconstitution, leading to poor control of virus replication, which is associated with increased mortality, 1 was suggested. 9,10,17 In the current study, in contrast, a wide variety of CMV DNA load cutoffs were in place for PET initiation.…”

“…1,2 Although PET usually succeeds in preventing development of CMV disease, concern has been raised as to the potential deleterious impact of CMV DNAemia, in the absence of CMV disease, on patient survival. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] In this regard, recently published data derived from large cohorts pointed to an association between either CMV DNAemia or pp65 antigenemia, at any level, with increased risk of overall (OM) and nonrelapse mortality (NRM) in the first year after allo-HSCT, independent of the use of PET. 7,13 Several studies comprising much more limited cohorts supported these associations, but only in patients experiencing CMV DNAemia episodes who received PET.…”

“…7,13 Several studies comprising much more limited cohorts supported these associations, but only in patients experiencing CMV DNAemia episodes who received PET. 9,10,15,17 In a recently published meta-analysis, CMV DNAemia was indeed linked to increased mortality, but this effect was notably modulated by transplant modality and use of PET. 19 The advent of letermovir will certainly foster a paradigm shift in CMV infection management in allo-HSCT recipients 20,21 ; however, PET may conceivably continue to be used as a first-choice option in a subset of patients, perhaps those at lowest risk of CMV-related complications, or in patients who develop breakthrough episodes of CMV DNAemia while on prophylaxis with this drug.…”