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Impact of Cytomegalovirus (CMV) Viral Load on Probability of Spontaneous Clearance and Efficacy of Pre-Emptive Therapy Among CMV Seropositive Allogeneic Stem Cell Transplant Recipients

Year: 2017

Type: article

Abstract: Background: The optimal threshold to initiate pre-emptive CMV therapy in SCT recipients remains to be defined. Methods: Single center retrospective analysis of 94 CMV seropositive allogeneic SCT recipients (Jan 2013-Apr 2015). Plasma CMV PCR was performed twice a week for the first 100 days, and at least weekly while on anti-CMV therapy. Likelihood of achieving spontaneous clearance (resolution of viremia in the absence of therapy) was determined by logistic regression models. CMV-related outcomes and non-relapse mortality (NRM) were assessed among patients who received antiviral therapy. Results: 70 patients (75%) developed CMV viremia. Median time to reactivation was 15 (6-31) days post-SCT. Peak viremia ≥200 IU/mL was strongly associated with failure to achieve spontaneous clearance (RR, CI95%: .08, .03-.22). Patients with peak viremia <200 IU/mL had a higher probability of spontaneous clearance independent of other risk factors (Table 1). Among treated patients, the median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350 IU/mL (15 vs 32 days; P = .001). Patients who started therapy at CMV ≥350 IU/mL were less likely to eradicate CMV by post-treatment day 28 (34 vs 71%; P = .02). Unresolved CMV viremia by day 28 was associated withincreased risk of therapeutic failure (35 vs 0%; P = .001) and recurrent viremia (84 vs 39%; P = .005). NRM at one year post-SCT was higher in patients with unresolved viremia by day 28 but this finding did not reach statistical significance (32 vs. 10%, P = .08). Therapeutic failure was associated with high NRM: 56, 78, 100% at 100, 200 and 365 days post-SCT (log-rank P < .0001; Figure 1).Table 1Probability of spontaneous clearance of CMV viremia in high-risk SCT patientsVariableUnivariateMultivariateRR (95% CI)P valueRR (95% CI)P valuePeak CMV < 200 IU/mL11.8(4.5-31)<.00019.12(2.96-28)<.0001Lymphoid malignancy*.29(.1-1.2).08.61(.16-2.4).48Steroids†.89(.4-2.0).8ATG‡.37(.2-.8).01.89(.5-1.7).72CMV seropositive donor2.95(1.1-8.1).041.87(.9-4.0).10Mismatch or unrelated donor§.27(.1-.6).001GVHD1.9(.6-5.7).281.07(.48-2.4).75* Includes acute lymphoblastic leukemia(n = 13), lymphoma(n = 15) and multiple myeloma (n = 1).† More than .5 mg/kg/day of prednisone or equivalent.‡ 66 patients.§ HLA-matched(n = 40) and mismatched(n = 21) unrelated donors, including 2 cords. Open table in a new tab * Includes acute lymphoblastic leukemia(n = 13), lymphoma(n = 15) and multiple myeloma (n = 1). † More than .5 mg/kg/day of prednisone or equivalent. ‡ 66 patients. § HLA-matched(n = 40) and mismatched(n = 21) unrelated donors, including 2 cords. Conclusions: Among CMV seropositive SCT patients, peak CMV viremia ≥200 IU/mL is associated with >90% reduction in the probability of spontaneous clearance, and is a reasonable cutoff for pre-emptive therapy. Initiation of therapy at CMV values ≥350 IU/mL is associated with adverse outcomes.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2016.12.364